Angina Mngmt

8/6/2019 Angina Mngmt

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MmA national clinical guideline

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CoPiesofallsigngUidelinesaReaVailableonlineatWWW.sign.aC.Uk

Scottish Intercollegiate Guidelines Network

SIGN



keYtoeVidenCestateMentsandgRadesofReCoMMendations

leVelsofeVidenCe

1++ High quality meta-analyses, systematic reviews of randomised controlled trials(RCTs), or RCTs with a very low risk of bias

1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a lowrisk of bias

1-

Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias2++ High quality systematic reviews of case control or cohort studies

High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+ Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2 - Case control or cohort studies with a high risk of confounding or bias andasignifcantriskthattherelationshipisnotcausal

3 Non-analytic studies, eg case reports, case series

4 Expert opinion

GRADES OF RECOMMENDATION

Note: The grade of recommendation relates to the strength of the evidence on which therecommendation is based. It does not reect the clinical importance of the recommendation.

a At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++ and directly applicable to the target population ; or

A body of evidence consisting principally of studies rated as 1+, directly applicableto the target population, and demonstrating overall consistency of results

b A body of evidence including studies rated as 2++, directly applicable to the target

population, and demonstrating overall consistency of results ; or Extrapolated evidence from studies rated as 1++ or 1+

C A body of evidence including studies rated as 2+, directly applicable to the targetpopulation and demonstrating overall consistency of results ; or

Extrapolated evidence from studies rated as 2++

d Evidence level 3 or 4 ; or

Extrapolated evidence from studies rated as 2+

GOOD PRACTICE POINTS

Recommended best practice based on the clinical experience of the guidelinedevelopment group

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Scottish Intercoegite Guideines Netork

Mngement o stbe ngin

A natina cinica guideine

Februar 2007



© Scttish Intercegiate Guideines NetwrkISBN 1 899893 89 XFirst pubished 2007

SIGN cnsents t the phtcping f this guideine fr thepurpse f impementatin in NHSSctand

Scottish Intercoegite Guideines Netork28 Thiste Street, Edinburgh EH2 1EN

.sign.c.uk



1 INTRODUCTION

1 Introduction

1.1 wHy IS aNGINa IMpORTaNT?

The recrded preaence f angina aries great acrss UK studies. The Scttish Heath Sure (2003)reprts the preaence f angina, determined b the Rse Angina Questinnaire t be 5.%and 6.7% in maes aged 55-64 and 65-74 respectie.2 Fr the same age grups in wmen theequiaent rates were 4% and 6.8%. This cmpares with genera practitiner (GP) recrd datain the British Regina Heart Stud frm acrss the UK f 9.2% and 6.2% fr men in the sameage grups.3 The aerage GP wi see, n aerage, fur new cases f angina each ear. 4

Practice team infrmatin submitted b Scttish genera practices t Infrmatin SericesDiisin (ISD) Sctand aws the cacuatin f an annua preaence rate fr Sctand (theproportion of the population who have consulted their general practice because of a denitediagnsis f angina based n ISD’s standard mrbidit gruping). In the ear ending March 2005the annua preaence rate is gien as 8.3 fr men and 7.6 fr wmen per ,000 ppuatin.This equates t an estimated number f patients seen in Sctand in that ear fr angina f

42,600 with 68,200 patient cntacts.5

A diagnosis of angina can have a signicant impact on the patient’s level of functioning. In onesure, angina patients scred their genera heath as twice as pr as thse wh had had astrke.6 In anther sure, patients had a w ee f factua knwedge abut their iness andpr medicatin adherence.7 A Taside stud shwed that in patients with angina, smptmsare ften pr cntred, there is a high ee f aniet and depressin, scpe fr ifestechange and an nging need fr frequent medica cntact.8

1.2 THE NEED fOR a GUIDElINE

In recent ears there has been a decine in the rate f majr crnar eents and death frmcrnar heart disease (CHD).9 Hweer, data frm the British Regina Heart Stud based n

GP records which included Scotland has shown an annual increase of 2.6% in rst diagnosedangina in the 20 ears f fw up t the ear 2000 in maes aged 40-59 at entr.3 This increasereects the diagnosis as it occurred in clinical practice without objective criteria to conrmthe presence f undering CHD. The rise in the rate f new angina diagnses eiminates anera fa in the diagnsis f CHD.

Genera practitiners are being adised t ensure that patients presenting with smptmscnsistent with angina are rapid assessed. The deepment f rapid access chest pain cinicshas been encuraged t aw this t happen.0 Eidence based diagnstic practice and thepriritisatin f inestigatin in patients with smptms cnsistent with angina are required.

1.3 aNGINa aS a SyMpTOM

Angina is used t describe a cinica sndrme f chest pain r pressure precipitated b actiitiessuch as eercise r emtina stress which increase mcardia gen demand. Athughcassica stabe angina can be predictabe in nset, reprducibe and reieed b rest r gcertrinitrate, other factors and circumstances can inuence its development. Angina can be causedb arius cardiascuar cnditins but this guideine is restricted t the cinica situatinwhere reduced mcardia perfusin is due t arteria narrwing resuting frm underingatherscertic crnar heart disease. A sma minrit f patients hae bjectie eidencef mcardia ischaemia in the absence f an bius structura abnrmait f the crnararteries.

Stabe angina is usua assessed in the utpatient setting. It is imprtant when taking a cinicahistr t identif and manage apprpriate thse patients whse smptms ma be due tthe mre seere changes f paque ersin and rupture ccurring as part f the spectrum f

acute crnar sndrme (see SIGN guideline 93 on acute coronary syndromes).



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2 Dignosis nd ssessment

2.1 ESTaBlISHING a DIaGNOSIS

Angina is a smptm that suggests that an indiidua ma hae undering CHD. Inestigatinto conrm the severity and extent of underlying CHD may also allow management strategies tobe deeped and ptimise cardiascuar risk reductin.3 A signicant proportion of patientswith chest pain ma nt hae angina and assessment shud as tr t identif aternatiediagnses at an ear stage.

Angina ften aries in seerit and patients wh hae unstabe angina (acute crnar sndrme)are utside the remit f this guideine, as these patients usua require mre urgent andimmediate management (see SIGN guideline 93 on acute coronary syndromes).

Patients with stabe angina are usua managed in the primar care setting, but ma present ina number f heathcare settings. An initia diagnsis f angina can be made within primar carebut this should be supported by further assessment and risk stratication, which will normallyrequire speciaist input.

2.. ClINICAl ASSESSMENT

Patients with stabe angina shud hae the diagnsis made, where pssibe, fwing a carefubtained cinica assessment. Cinica histr is the ke cmpnent in the eauatin f thepatient with angina; ften the diagnsis can be made n the basis f cinica histr ane. Whiea number f scring sstems are aaiabe t assess patients with chest pain and stabe angina,an accurate cinica assessment is f ke imprtance. There are seera tpica characteristicsf stabe angina which shud increase the ikeihd f undering CHD. These incude: 4

tpe f discmfrt – ften described as tight, du r hea

catin – ften retrsterna r eft side f chest and can radiate t eft arm, neck, jaw andback

reatin t eertin – angina is ften brught n with eertin r emtina stress and easedwith rest

duratin – tpica the smptms ast up t seera minutes after eertin r emtinastress has stpped

ther factrs – angina ma be precipitated b cd weather r fwing a mea.

The predminant features described b sme patients are discmfrt and heainess r breathessness, rather than pain. Chest discmfrt, irrespectie f its site, is mre ike t beangina when precipitated b eertin and reieed b rest. It is as characteristica reieedb gcer trinitrate. Nt a patients wi present with tpica characteristics and the cinicianshud be aware f ther smptms such as breathessness and burping which ma be theinitia presenting smptm.

Angina can be graded b seerit n the Canadian Cardiascuar Sciet (CCS) cass scae f I-Iv5 (see Table 1).

Table 1: Canadian Cardiovascular Society Angina Classication

Css Descrition

Cass I ordinar actiit such as waking r cimbing stairs des nt precipitate angina

Cass II Angina precipitated b emtin, cd weather r meas and b waking upstairs

Cass III Marked imitatins f rdinar phsica actiit

Cass Iv Inabiit t carr ut an phsica actiit withut discmfrt – angina smptms

ma be present at rest.

2 DIaGNOSIS aND aSSESSMENT



MaNaGEMENT Of STaBlE aNGINa

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The ikeihd f a diagnsis f angina increases with the number f cardiascuar risk factrsin indiidua patients. These incude:

smking

hpertensin

diabetesfamily history of CHD (rst degree relative – male <55 years/female <65 years)

raised chester and ther ipids.

These risk factrs are best initia addressed in the primar care setting where ifeste adicecan be prided and supprt ffered, where necessar. If smptms persist, mre bjectieeauatin f smptms ma be necessar t estabish the seerit f an undering CHD. Inadditin t assessment f cnentina risk factrs, (see SIGN guideline 97 on risk estimationand the prevention of cardiovascular disease)73 patients shud hae the fwing eauated:

bd mass inde (BMI) r waist circumference

murmur eauatin

haemgbin ee

fasting bd gucsethrid functin

depressin and scia isatin

phsica actiit.

A number f scring sstems hae been prpsed t assess the seerit and prgnstic impactf angina.6,7 Whie these scring sstems ma be accurate in the patient grups incuded inthe chrts studied, their use in rutine cinica practice cannt be recmmended, but themay have a role in inuencing the clinical decision making process.

When a general practitioner identies a patient with stable angina, further assessment at acardig utpatient cinic is desirabe.

Patients with suspected angina shud hae a detaied initia cinica assessment whichincudes histr, eaminatin and an assessment f bd pressure, haemgbin, thridfunctin, chester and gucse ees.

Thse patients wh shud be cnsidered fr ear referra t secndar care incudethse with new nset angina and thse with estabished crnar heart disease with anincrease in smptms.

2..2 NoN-CARDIAC CHEST PAIN

Angina pain is not usually sharp or stabbing in nature. It is not usually inuenced by respirationr eased with antacids and simpe anagesia.

The initia cinica assessment is imprtant as it ma reduce aniet and distress resuting inunnecessar hspita admissins and cnsutatins.8 lw risk patients, such as ung wmenwith atpica smptms, shud be assessed in primar care where pssibe. Much f thisassessment incudes epaining smptms, discussing cncerns and priding reassurancewhere necessary. A diagnosis of non-cardiac chest pain should be given early and condentlyas crrect management ma reduce mrbidit.9

A rehabiitatin prgramme based n cgnitie behaiur principes fr patients with chestpain but nrma crnar arteries, fund that thse wh cntinued t attribute smptms tcardiac causes had wrse utcmes.20

If the diagnsis is uncertain, cinicians shud nt gie the impressin that the patient hasangina. This may lead the patient to have false beliefs, which may be difcult to changeeen after further inestigatins hae rued this ut.



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2..3 DIAGNoSTIC ToolS

Electrocardiography

A baseine 2 ead eectrcardigram (ECG) shud be perfrmed in eer patient with suspectedangina.2 A nrma 2 ead ECG des nt ecude a diagnsis f crnar heart disease.22 An

abnrma resting ECG increases the prbabiit that a patient has CHD, but gies n indicatinas t the seerit f an assciated bstructie crnar heart disease.23 A 2 ead ECG can ashighlight the presence of atrial brillation or left ventricular hypertrophy. The interpretation of resting r eercise ECGs is peratr-dependent.24

Exercise tolerance testing

The majrit f patients with suspected angina wi be referred fr eercise terance testing(ETT), which is as knwn as eercise ECG r stress ECG. Eercise is usua perfrmed btreadmi testing r n a static bicce and ma be unsuitabe fr patients wh hae pr mbiit,periphera arteria disease r imiting respiratr r muscuskeeta cnditins.

The sensitivity and specicity of ETT in establishing the diagnosis of CHD is dependent onthe chrt f patients studied. Sensitiit is higher in patients with tripe esse disease and

wer in patients with singe esse disease.25 The true diagnstic aue f eercise ECG iesin its relatively high sensitivity, but it is only moderately specic for the diagnosis of CHD inwmen.26

A nrma eercise test ma reassure man patients but it des nt ecude a diagnsis f CHD.A high abnrma ETT resut is an indicatin fr urgent further inestigatin.

Myocardial perfusion scintigraphy

Mcardia perfusin scintigraph (MPS) with eercise r pharmacgic stress is an accurateand nn-inasie inestigatin which reiab predicts the presence f CHD.27 Mcardiaperfusin scintigraph ma be the apprpriate initia diagnstic test in patients with pre-eistingECG abnrmaities (eg eft bunde branch bck) r in thse unabe t adequate eercise andas part f the diagnstic strateg fr suspected CHD in pepe with wer ikeihd f CHD.28 It is as auabe in femaes wh ma hae a w risk f undering CHD but a high risk f a falsely positive ETT and in patients where identication of regional ischaemia would be of aue (eg prir t PCI). Mcardia perfusin scintigraph prides auabe independent andincremental prognostic information to that provided by ETT and this enables risk stratication

f patients which infrms treatment decisins.29

C ptients ith susected ngin shoud usu be inestigted b bseineeectrocrdiogrm nd n exercise toernce test.

B ptients unbe to undergo exercise toernce testing or ho he re-existingeectrocrdiogrm bnormities shoud be considered or mocrdi erusionscintigrh.

Coronary angiography

Crnar angigraph is the traditina benchmark inestigatin fr estabishing the nature,anatm and seerit f CHD. It is an inasie inestigatin and carries a mrtait risk f arund 0.% fr eectie prcedures.30 It requires referra t a cardigist and is best reseredfr thse patients wh are at high risk r cntinue t hae smptms despite ptima medicatreatment and ma require reascuarisatin. It ma as pride auabe infrmatin regarding

auar and eft entricuar functin.

Crnar angigraph shud be cnsidered after nn-inasie testing where patientsare identied to be at high risk or where a diagnosis remains unclear.

2 DIaGNOSIS aND aSSESSMENT




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Other investigations

Newer inestigatins incuding stress echcardigraph, magnetic resnance perfusin imaging(MRI) and mutisice cmputed tmgraph (CT) scanning are as effectie in estabishing adiagnsis f CHD when perfrmed b trained and skied teams.3-33 These inestigatins are

nt part f rutine cinica practice in NHSSctand, athugh their use ma becme mrewidespread as cinica and ecnmic eauatins f their effectieness becme aaiabe.

2.2 MODElS Of CaRE

A variety of models have been developed to facilitate prompt identication and optimummanagement f patients with angina frm thse with ptentia ess seere causes f chestpain. These mdes f care hae been designed in aring was emphasising the deepmentof a service which reects local health needs and demands. While many of these serviceshae a triage re, their design faciitates the ear detectin f patients wh ma hae seereCHD who would benet from early intervention. Optimum management of angina requiresreassurance f w risk patients whie apprpriate identifing high risk patients and makingthe most efcient use of available resources.

Rapid access chest pain cinics (RACPCs) hae been adcated as a successfu mde f referrat secndar care fr angina patients. These hae been in eistence fr man ears. The NatinaSerice Framewrk fr Crnar Arter Disease suggested mre f these cinics shud be setup and red ut acrss Engand and Waes t assess patients within tw weeks f primarcare referra.34 No evidence was provided to explain the specic target of two weeks. Thesecinics are run in a ariet f was, depending n ca resurces, where patients can be seen bcardigists, speciaist registrars, nurse speciaists r GPs with specia interest in cardig.

one detaied meta-anasis inestigated a range f methds, incuding rapid access chestpain cinics, in the diagnsis and management f acute crnar sndrmes (ACS), suspectedmcardia infarctin (MI) and eertina angina.2 Weak eidence was fund t suggest thatRACPCs ma be assciated with reduced admissin t hspita f patients with nn-cardiac

pain, better recgnitin f ACS, earier speciaist assessment f eertina angina and earier diagnsis f nn-cardiac chest pain. In a simuatin eercise f mdes f care fr inestigatinf suspected eertina angina, RACPCs were predicted t resut in earier diagnsis f bthconrmed CHD and non-cardiac chest pain than models of care based around open accessexercise tests or routine cardiology outpatients, but they were more expensive. The benetsf RACPCs disappeared if waiting times fr further inestigatin (eg angigraph) were ng(si mnths).

The eidence arund the cst effectieness f RACPC fr patients with suspected angina is erimited. one stud shwed perating such a cinic can be cst saing, cmpared t standardcare, ptentia reducing csts b abut £60 per patient, with the saings cming frm fewer unnecessar hspitaisatins.35 However, the study is weak, results are very setting specic andma nt generaise t ther settings.

B fooing initi ssessment in rimr cre, tients ith susected ngin shoud,wherever possible, have the diagnosis conrmed and the severity of the underlyingcoronr hert disese ssessed in the chest in eution serice hich oers theeriest ointment, regrdess o mode.



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3 phrmcoogic mngement

This sectin deas with drugs that reiee and preent angina smptms.

3.1 DRUG MONOTHERapy TO allEvIaTE aNGINa SyMpTOMS

A the studies reprted were carried ut n a mied ppuatin with maes as a majrit andincuded arius age grups and patient entr criteria. Ppuatins f patients with and withutpast medica histries f MI, heart faiure and ther cardiac and nn-cardiac cmrbidities werereprted. The ppuatins in the trias resembe the Scttish ppuatin wh are treated fr chest pain resuting frm CHD. Drugs that are unicensed fr the treatment f CHD in the UKare nt incuded in the guideine.

3.. BETA BloCKERS

Beta bckers impre gen supp and demand baance b reducing heart rate and bdpressure, decreasing end sstic stress and cntractiit and prnging diaste, awing mrecoronary ow.

Meta-analyses have shown that beta blockers remain the rst line drugs for the long termpreentin f chest pain resuting frm CHD.36-38 This is because f their ptentia t reducemrtait in patients with acute MI r heart faiure.39,40 one bseratina stud suggests amortality benet of beta blockers in patients with stable CHD and without a past medicalhistr f MI r heart faiure.4

Mst randmised cntred trias (RCTs) hae used der beta bckers such as prpran,metpr and aten fr the treatment f stabe angina,36-38 and newer beta bckers such asbispr hae as been shwn t be effectie.42 The efcacy of beta blockers is due to a classeffect mediated thrugh bcking beta adrenceptrs rather than t indiidua characteristics f each drug. Cmrbidit, eg heart faiure, and ther factrs such as cmpiance and cst shud

be cnsidered when seecting an indiidua beta bcker. The British Natina Frmuar (BNF) indicates that the usua beta bcker regimens are: aten00 mg dai in singe r diided dsages, metpr 50-00 mg tw t three times dai r bispr 5-20 mg nce dai. Dses shud be taired indiidua t ensure maimum betablockade depending on the sensitivity of the patient to specic drugs. Resting heart rate lessthan 60 beats per minute is an indicatin f beta bckade. 43

Beta bckers are cntraindicated in patients with seere bradcardia, atrientricuar (Av)bck, sick sinus sndrme, decmpensated heart faiure and asthma.43 Diabetes meitus isnt a cntraindicatin t beta bckers.

a Beta blockers should be used as rst line therapy for the relief of symptoms of stablengin.

3..2 CAlCIUM CHANNEl BloCKERS

Cacium channe bckers (CCBs) inhibit cacium transprt and induce smth musce reaatin.

Meta-anases36-38 and RCTs44,45 hae shwn that CCBs are genera as effectie as beta bckersin reducing angina smptms.

Few studies hae direct cmpared indiidua CCBs using angina smptms as a cinicaendpint. In a sma RCT ditiazem and amdipine were simiar in impring eerciseterance in patients with CHD.45 The chice f CCB ma depend n cmrbidit and druginteractins.

Rate-imiting CCBs (erapami and ditiazem) are cntraindicated in heart faiure and in patients

with bradcardia r Av bck. Patients with heart faiure and angina ma be safe treated withthe dihdrpridine deriaties amdipine r fedipine46,47 (see also SIGN guideline 95 onthe management of chronic heart failure).48

3 pHaRMaCOlOGICal MaNaGEMENT




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There is conicting evidence regarding the safety of nifedipine in patients with angina. A meta-anasis has indicated that nifedipine mntherap r shrt-acting nifedipine in cmbinatinwith ther anti-angina drugs ma increase the incidence f cardiascuar eents, mainangina episdes.49

Prinzmeta (asspastic) angina is a rare frm f angina in which pain is eperienced at rest rather than during actiit. It is caused b narrwing r ccusin f prima crnar arteries due tspasm and cannt be diagnsed b crnar angigraph. Beta bckers shud nt be used inthis frm f angina because the ma wrsen the crnar spasm.50 Patients with this cnditinma be treated effectie with a dihdrpridine deriatie CCB such as amdipine.5

B ptients ith prinzmet (vasospastic) ngin shoud be treted ith dihdroridinederitie ccium chnne bocker.

3..3 PoTASSIUM CHANNEl ACTIvAToRS

There are few studies on the efcacy of nicorandil in the treatment and prevention of chest pain.one RCT shwed that nicrandi was cmparabe t ditiazem in reducing angina.52 Anther tria demnstrated that nicrandi was as effectie as amdipine in patients with smptmaticstabe angina.53 In another RCT of over 5,000 patients, nicorandil was shown to signicantlyreduce the cmbined endpint f CHD death, nn-fata mcardia infarctin, r unpannedhspitaisatin fr cardiac chest pain (5.5% t 3.% hazard rati 0.83, 95% condenceintera, CI, 0.72 t 0.97; p=0.04).54 A cst effectieness anasis based n the resuts f thistria estimated that the additina csts f adding nicrandi t standard care fr patients withangina were ffset b the reduced hspitaisatin csts.55

3..4 NITRATES

These drugs act direct n the ascuar smth musce t prduce enus and arteria diatatin,reducing pre-ad, after-ad and gen demand.

Nitrates are effectie drugs in the preentin and treatment f angina. In meta-anases, there

was no signicant difference in the anti-anginal efcacy between long-acting nitrates and betabckers r CCBs.36,37 In a mre recent RCT, the CCB amdipine was shwn t be mre effectiethan nitrates in cntring eercise-induced angina in eder patients with stabe CHD. 56

Subingua gcer trinitrate is effectie fr the immediate reief f angina and can as be usedt preent ischaemic episdes when used befre panned eertin.57,58

a Subingu gcer trinitrte tbets or sr shoud be used or the immedite reieo ngin nd beore erorming ctiities tht re knon to bring on ngin.

Nitrate tolerance can be avoided by prescribing modied release long acting preparations or b asmmetric dsing.59 Such regimens can be cnfusing t patients and cud ead t nn-compliance and nitrate tolerance. Modied release oral nitrates that are given once daily providetherapeutic pasma nitrate ees er the initia few hurs fwing ingestin. Cmpiancehas been shwn t impre when transferring frm mutipe dse regimens t nce-dairegimens.60,6 The w pasma nitrate ee at 24 hurs fwing ingestin appears t minimiseterance.62,63

The main side effect f nitrates is headache, which usua wears ff after cntinuus use, but in smepatients this cud becme interabe and necessitate change t anther anti-angina drug.



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An economic model compared a single daily dose regimen using a modied release formulationwith a twice-dai dse regimen, and assumed that better cmpiance with the singe dse (88%s 68%) wud impre smptm cntr and resut in fewer isits t GPs.62 The tw regimenshad er simiar annua csts (£248 s £250). The sensitiit anasis shwed that the resutis high sensitie t changes in the assumed cmpiance rates and drug csts. In Sctand,

prescriptin f a generic drug fr the tw dse regimen wud be cst saing cmpared t thesingle dose modied release option.

a ptients ho re intoernt o bet bockers shoud be treted ith either rte imitingccium chnne bockers, ong-cting nitrtes or nicorndi.

3..5 EFFECT oF oTHER DRUGS oN ANGINA

Iabradine, a seectie If --channe inhibitr, acts t wer heart rate. In a dube bind randmised

parallel-group trial ivabradine was shown to have equivalent anti-anginal efcacy to atenolol inpatients with stabe angina.64 While symptomatic benet has been clearly demonstrated longterm prtectin against cardiascuar eents has et t be determined.

3.2 COMBINaTION THERapy TO allEvIaTE aNGINa SyMpTOMS

3.2. ADDING CAlCIUM CHANNEl BloCKERS To BETA BloCKERS

A meta-anasis f 22 RCTs demnstrated that the cmbinatin f a beta bcker with a CCB ismre effectie than mntherap in impring eercise terance. Time t mm ST-segmentdepression, total exercise duration and time to onset of anginal pain were signicantly increasedwith the cmbined therap cmpared t beta bcker ane (b 8, 5 and 2%, respectie).This benet was only shown to be signicant within six hours of drug intake. 65

Adding ditiazem t beta bckers prduces a dse-dependent imprement in smptm cntrand eercise terance.66 The British Natina Frmuar suggests cautin as this cmbinatinma cause seere bradcardia and heart bck in sme cases.43

Dihdrpridine deriaties are safe when cmbined with beta bckers. The cmbinatin f metpr with fedipine was shwn t be sight mre effectie than metpr ane inne RCT.67 This trial showed a statistically signicant improvement in time until end of exercisewith felodipine-metoprolol combination (10/100 mg) compared with metoprolol 100 mg(p=0.04) and fedipine 0 mg cmpared with metpr 00 mg (p=0.03). Fr time untionset of pain or time until 1-mm ST-depression there were no signicant differences amongthe treatment grups.

other RCTs hae shwn that adding CCBs t beta bckers, athugh safe, ffered er itte r no benet in relief of anginal symptoms.68-70

a when deute contro o ngin smtoms is not chieed ith bet-bockde ccium chnne bocker shoud be dded.

Rate-imiting cacium channe bckers shud be used with cautin when cmbinedwith beta bckers.

3.2.2 ADDING NITRATES oR NICoRANDIl To oTHER ANTI-ANGINAl DRUGS

Adding issrbide mnnitrate t a beta bcker 7 r t a CCB72 signicantly improvesperfrmance n a range f cinica endpints. Adding nicrandi t ther anti-angina drugs waseffectie in reducing cmbined cardiac eents. one f these cmpsite endpints was hspitaadmissin fr refractr angina. There was n primar endpint fr reducing chest pain. 54





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3.2.3 THE USE oF THREE DRUGS

The eidence fr cmbining three drugs is er imited. In ne stud the cmbinatin f ngacting nitrates, beta bckers and CCBs was ineffectie in impring eercise testing whencmpared t a cmbinatin f tw f the drugs.69

The patients incuded in these trias were mst stabe patients wh perhaps did nt requireanther drug t cntr their angina. The were usua tested as t whether adding anther drug wud reduce their eisting angina, measured b the number f angina episdes, eerciseterance and amunt f gcer trinitrate used. In ‘rea ife’ situatins patients are gien asecnd r a third anti-angina drug usua when the becme refractr t ne r tw drugs.More randomised trials are needed to test the efcacy of adding a third anti-anginal drug topatients whse angina is nt ptima cntred n a cmbinatin f tw drugs.

Patients whse smptms are nt cntred n maimum therapeutic dses f tw drugsshud be cnsidered fr referra t a cardigist.

3.3 DRUG INTERvENTIONS TO pREvENT NEw vaSCUlaR EvENTS

Patients with angina due t CHD are at risk f cardiascuar eents and are eigibe fr secndarpreentatie treatments t wer their risk f cardiascuar disease (CvD). These interentinsare cnsidered in mre detai in SIGN guideine 97 n risk estimatin and the preentin f cardiascuar disease.73

3.3. ANTIPlATElET THERAPy

Eidence frm 287 studies ining a tta f 35,000 patients with cardiascuar diseaseincuding stabe angina has shwn that antipateet therap, main with aspirin, gien in adose ranging from 75 to 150 mg daily led to a signicant reduction in serious vascular events,nn-fata mcardia infarctin, nn-fata strke and ascuar mrtait.74

Enteric cated prducts d nt preent the majr gastrintestina cmpicatins f aspirin therap

and are signicantly more expensive than the standard dispersible formulation.75-77

3.3.2 lIPID loWERING THERAPy WITH STATINS

A meta-anasis f data frm 4 randmised trias f statins ining 90,056 patients incudingpatients with stable angina has shown the overall benet of statin therapy. There was a signicantreductin in a-cause and crnar mrtait, mcardia infarctin, the need fr crnarreascuarisatin and fata r nn-fata strke.78

a a tients ith stbe ngin due to theroscerotic disese shoud receie ong termstndrd sirin nd sttin ther.

3.3.3 ACE INHIBIToRS

The questin f whether patients with stabe angina but withut eft entricuar ssticdysfunction benet from angiotensin-converting enzyme (ACE) inhibition is controversial. Four large RCTs were identied which addressed this topic although the results are conicting. 79-82 When re-analysed in two meta-analyses of these and other trials, ACE inhibitors signicantlyreduced a cause and cardiascuar mrtait.83,84

The HoPE stud ined 9,297 high-risk patients with ascuar disease r diabetes pus nether cardiascuar risk factr withut histr f heart faiure r eft entricuar dsfunctin. Itshowed that ramipril was associated with signicant reductions in all-cause mortality, myocardialinfarctin and strke in these patients.79 The use f perindpri in the EURoPA stud ining3,655 patients with stabe crnar disease and n cinica eidence f heart faiure reduced therisk f cardiascuar death, mcardia infarctin r cardiac arrest.80 This signicant reduction

in cardiascuar eents is main due t the reductin in the incidence f nn-fata mcardiainfarctin. Unike the HoPE stud, the effect n a-cause mrtait did nt reach a statisticasignicant level. Subgroup analysis of the trial showed that benet from perindopril is mainlyin patients with histr f mcardia infarctin.



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Two other trials of ACE inhibitors did not show any benet in patients with stable coronary heartdisease. The PEACE tria using trandpri f 8,290 patients with n histr f cinica heartfaiure r echcardigraphic eidence f eft entricuar sstic dsfunctin did nt reea anbenet on cardiovascular events although the event rate was unexpectedly low.8 The studppuatin in this tria was f wer risk and receied mre intensie treatment f risk factrs

than did thse in the HoPE and EURoPA trias.

A smaer tria (QUIET) f ,750 patients with crnar heart disease and nrma eft entricuar function found that the ACE inhibitor quinapril did not signicantly affect clinical outcomes or the prgressin f crnar atherscersis.82 A patients recruited t this tria had undergnesuccessfu crnar angipast ining the reascuarisatin f at east ne crnar arter.

A meta-anasis f si randmised trias, incuding 33,500 patients with crnar arter diseaseand preserved left ventricular systolic function showed that ACE inhibitors signicantly reducedcardiascuar (reatie risk, RR 0.83, CI 0.72 t 0.96, absute risk reductin, ARR 0.86%,p=0.0) and a-cause mrtait (RR 0.87, CI 0.8 t 0.94, ARR .06%, p=0.0003). 83

When the ndings of the HOPE, EUROPA, and PEACE trials were combined in a meta-analysisof 29,805 patients, ACE inhibitors signicantly reduced all-cause mortality (7.8 vs 8.9%,

p=0.0004), cardiascuar mrtait (4.3 s 5.2%, p=0.0002), nn-fata mcardia infarctin(5.3 s 6.4%, p=0.000) and a strke (2.2 s 2.8%, p=0.0004).84 Athugh PEACE and QUIET,which did not show a benet of ACE inhibitors among their populations, both recruited patientsat apparent wer CvD risk, the PEACE tria was underpwered rather than affected b wcardiascuar eent rates in the stud ppuatin.

Patients with eft entricuar sstic dsfunctin (lvSD) r heart faiure are at higher risk thanthose included in HOPE, EUROPA or PEACE and will gain relatively more benet from ACEinhibitr therap.84 Sstematic reiews in patients with chrnic heart faiure r lvSD indicateabsute risk reductins ranging frm 3.8 - 6%.85,86 A patients with stabe ascuar disease arelikely to derive some benet from these drugs, to a degree approximately proportional to theee f baseine risk.

a a tients ith stbe ngin shoud be considered or tretment ith ngiotensin-conerting enzme inhibitors.





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4 Interention crdioog nd crdic surger

4.1 CORONaRy aRTERy aNaTOMy aND DEfINITIONSThe three principal coronary arteries are the left anterior descending (LAD), circumex (Cx)and right crnar arteries (RCA). The right and eft crnar arteries arise frm their respectiecrnar stia just abe the artic ae. The RCA suppies the right side f the heart andtpica terminates as the psterir descending crnar arter supping the diaphragmatic(inferir) surface f the eft entrice. The eft crnar arter cntinues fr a ariabe distanceup t 3 cm as the eft main stem (lMS) befre diiding int lAD and C crnar arteries. Theeft crnar arter branches supp the anterir and atera was f the eft entrice and themajrit f the septum. The cinica imprtant distributins f crnar arter disease are:

eft main stem disease

singe, dube r tripe esse crnar arter disease (SvD,DvD,TvD) depending n thenumber f principa arteries diseased.

Mutiesse disease tpica refers t disease in mre than ne crnar arter and is nt thesame as TvD.

Fwing crnar angigraph, and assessment f eft entricuar functin, patients ma becnsidered fr crnar reascuarisatin b PCI (percutaneus interentin) r CABG (crnararter bpass grafting).

The principa indicatins fr reascuarisatin are smptmatic reief and prgnstic gain(increased ife epectanc). Pubished guideines87 recmmend reascuarisatin fr prgnsticand symptomatic benet in patients with the following anatomy:

signicant LMS disease (>50% stenosis), or

prima three esse disease, r

tw esse disease ining the prima lAD.

The benet is greatest in patients with left ventricular dysfunction and/or evidence of reversibleischaemia at w r mderate wrkads n eercise testing. 87,87

Athugh nt receiing prgnstic adantage, the fwing grups f patients ma receiesymptomatic benet from surgical revascularisation:

thse with singe esse disease nt ining the lAD88-90

thse with tw esse disease nt ining the lAD.89-9

4.2 CHOICE Of REvaSCUlaRISaTION TECHNIqUE

Fwing the decisin t interene, the majr cnsideratin is whether this shud be undertakenby PCI or surgery. Coronary artery bypass grafting has historically been the rst line option butwith the deepment f stenting with PCI, the re f surger has been chaenged.

The chice f reascuarisatin technique ines carefu cnsideratin f medica and surgicasuitabiit, but infrmed patient chice must be f primar cncern. In the cntet f stabe anginawhere an interentin is essentia eectie, an adequate amunt f time can be acatedt aw apprpriate cinica decisin making and fu infrmed patient decisin making.Idea, reascuarisatin ptins shud be jint cnsidered b a mutidiscipinar “HeartTeam” ining discussin between cardiac surgens, cardiac anaesthetists, interentinacardigists and the patient.

Crnar arter bpass grafting and percutaneus crnar interentins are bthapprpriate ptins fr the aeiatin f angina smptms.



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4.2. PERCUTANEoUS CoRoNARy INTERvENTIoN

Percutaneous coronary intervention denes angioplasty or percutaneous transluminal coronaryangioplasty (PTCA) where the artery is dilated by inating a ne balloon. In addition, PCI includesstenting which involves dilating the artery by angioplasty and then inserting a ne lattice scaffold

t preent the arter frm reciing (uncated stent). Mre than 90% f PCI prcedures nwine impantatin f ne r mre crnar stents. Stent techng is deeping rapidand stents ma be impregnated with drugs t preent r retard endtheiaisatin and reducerestensis (cated, r drug euting stents).

Seera RCTs hae shwn that bth sirimus and pacitae cated stents reduce the needfr repeat reascuarisatin b arund 50% when cmpared t uncated stents.92-94 one argeRCT shws n difference in repeat reascuarisatin r majr cardiac eent rates betweensirimus and pacitae cated stents.95 Cated stents dea re-endtheiaisatin and fr thisreasn dua antipateet therap (aspirin pus cpidgre) is recmmended fr perids f ateast three t si mnths pst prcedure as ppsed t n fur weeks fr uncated stents(see sections 5.2 and 5.3.4).

There are anecdta reprts f ate stent thrmbsis een after this time perid but n era

ecess in the incidence f stent thrmbsis has been shwn in an RCT.

4.2.2 CoRoNARy ARTERy ByPASS GRAFTING

Crnar arter bpass grafting has been used fr er three decades t bpass crnarstenses. It is a majr surgica prcedure with a w mrtait which ines the bpassing f a sectin f crnar arter narrwed b atherma with a sectin f heath saphenus einr interna mammar arter. In the UK Cardiac Surgica Register (UKCSR) fr 2003 the era30 da mrtait was 2.0%.96 This incudes saage prcedures perfrmed in patients wh mahae died een if surger had nt been undertaken.

Crnar arter bpass grafting ma be perfrmed using cardipumnar bpass wherea pump and genatr perfrm the re f the heart and ungs and permit the surgen t

perate n a sti nn-beating, prtected heart. This “n-pump” surger was cnsidered t berespnsibe fr sme f the deeterius effects fwing CABG such as cgnitie dsfunctinor exaggerated systemic inammatory response, and consequently off-pump coronary arterybpass surger has emerged as a technique t perfrm CABG withut cardipumnar bpass.Athugh cnsidered minima inasie, the prcedure sti ines a chest incisin. Minimainasie direct crnar bpass surger attempts t reduce the majr skin incisin but its useis nt widespread.

4.2.3 REvASCUlARISATIoN To RElIEvE ANGINA

Nine trials were identied which compare CABG with PCI without stenting97-05 and a further si which cmpare CABG with PCI utiising a stent.06-

Patient groups known to benet from CABG, eg those with LMS disease, were excluded

frm these trias and athugh caimed t be trias f mutiesse PCI, n arund 35% f randmised patients in these mutiesse trias had TvD. In a trias but ne,07 patients had gdeft entricuar functin and patients with diabetes accunted fr arund 5% f the tta.

Up t three ears pst interentin, studies demnstrate that PCI with uncated stents hasequiaent eent rates fr death, nn-fata MI and strke t CABG. Athugh surger is superir fr freedm frm angina and the need fr repeat reascuarisatin, this has t be baanced againstthe inasie nature f CABG. In the trias cmparing PCI with CABG, the aerage number f esses reascuarised is ess in the PCI grup. Incmpete reascuarisatin has deeterius effectsn ng term suria athugh this ma be attenuated b impred secndar preentin.2 Crnar arter bpass grafting is the preferred ptin if PCI cannt ffer an equiaent degreef reascuarisatin.

a ptients ho he been ssessed nd re nticited to receie smtomtic reierom rescuristion shoud be oered either coronr rter bss grting orercutneous coronr interentions.

4 INTERvENTIONal CaRDIOlOGy aND CaRDIaC SURGERy




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4.2.4 REvASCUlARISATIoN To IMPRovE loNG TERM PRoGNoSIS

Patients with signicant left main stem stenosis were excluded from randomised controlled trialseaing n eidence t supprt the re f PCI t impre ng term utcme in this grup. Inpatients with multivessel disease, there is no robust evidence for a survival benet with CABG.

one meta-anasis shwed a .9% absute suria adantage in faur f CABG er PCI fr all trials at ve years (p<0.02), but no signicant advantage at one, three, or eight years.3 Gienthe absence of signicant effect over a wider follow up period, it is possible that the apparentinterim suria adantage ma be due t a statistica anma. Patients randmised t PCI hadmore repeat revascularisations at all time points (risk difference; RD, 24% to 38%, p<0.001).With the use f stents, this RD was reduced t 5% at ne and three ears. As stenting wasnt aaiabe at the time sme trias were carried ut, a subgrup anasis was undertaken tanase pssibe differences in resuts f CABG s PCI with and withut stenting. At three ears,PCI with stent provided a statistically signicant reduction in non-fatal MI compared to CABG(RD -2.9%, 95% CI -5. t -0.6%; p=0.0). Athugh subsequent reascuarisatin was stimre frequent after PCI with stent than after CABG, the risk difference fr reascuarisatin intrias with stents was abut haf that bsered in trias withut stents.

For patients with diabetes, CABG provided a signicant survival advantage over PCI at four yearsbut nt at 6.5 ears. This subgrup anasis incuded patients frm the trias using PCI anemaking it ess reeant t current practice. In the trias f uncated stents PCI patients sti hadmre repeat reascuarisatins at three ears: risk difference 5% (95% CI 0 t 28%).

one meta-anasis cmparing CABG with PCI in isated lAD disease demnstrated CABG wasassciated with reduced mutipe aderse cardiac eents, reduced mrtait and mcardiainfarctin at a median fw up f three ears. In this stud, which incuded bth RCTs andbseratina data, si f the eight randmised trias used minima inasie techniques andne stud ined cated stents.4

The BARI tria is the singe argest randmised cntred tria f CABG s PCI. The PCI arm didnot use stents. Results compared various subsets of patients shown to derive prognostic benetin preius RCTs f CABG s medica therap. These subsets were three esse disease with r

without left ventricular (LV) dysfunction (left ventricular ejection fraction, LVEF < 50%), andtw esse disease incuding the prima lAD with r withut lv dsfunctin. After seenyears of follow up there were no statistically signicant mortality differences between CABGand PCI, een in patients with diabetes.5

We designed randmised cntred trias gie statistica aid data in a high seected grupf patients but frequent ess than 20% f eigibe patients are randmised. Registr studiesd nt hae the same statistica weight as RCTs as patients are nt randmised, but the mapride an insight t current practice in a mre cinica representatie ppuatin.

Registr studies suggest that CABG resuts in better ng term suria in patients with mutiessedisease compared to PCI with stenting. They also conrm the need for repeat revascularisationin the PCI grup.6,7 one registr and ne chrt stud demnstrate increased ng term

mrtait in patients with diabetes treated b PCI.8,9

Further registr data shw a reductin in ng term mrtait in thse patients with seere primalAD disease wh underwent CABG.6 The stent usage in this registr was w. A studiesconrm that CABG provides better relief of angina and less need for re-intervention. 20,2

a Patients with signicant left main stem disease should undergo coronary artery bypassgrting.

a ptients ith trie esse disese shoud be considered or coronr rter bssgrting to imroe rognosis, but here unsuitbe be oered ercutneous coronrinterention.

a ptients ith singe or doube esse disese, here otim medic ther is tocontro ngin smtoms, shoud be oered ercutneous coronr interention orhere unsuitbe, considered or coronr rter bss grting.



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4.2.5 CHoICE oF CoNDUIT IN SURGICAl REvASCUlARISATIoN

lng term patenc rates in ecess f 95% bend ten ears hae been reprted fr anastamsis f the eft interna mammar arter (IMA) t the lAD. This superir ng termpatency compared to saphenous vein grafts (SVG) leads to signicant reduction in long term

mrtait, subsequent mcardia infarctin, the need fr further peratin and freedm frmate cardiac eents.22,23

Reports on the use of both IMAs have reinforced the benets of arterial revascularisation. Inpatients where both IMAs were used, there was marginally improved long term survival at ve,ten and 5 ears (94%, 84% and 67% fr biatera IMA and 92%,79% and 64% fr singe IMA).This prognostic benet was accompanied by a reduced need for re-operation and PCI.24-26

The radia arter is as a suitabe cnduit and ma be used as a free graft appied t thearta r as a cmpsite “y” graft frm a eft IMA. Fie ear angigraphic patenc in a smanumber (n=50) f asmptmatic patients was 89% fr radia arter with IMA patenceceeding 94% and SvG patenc f 92%.27

In ne randmised tria f tta arteria reascuarisatin (TAR) cmparing IMA and SvG

grafts at ne ear, angina recurrence, the need fr reinterentin with PCI and actuariafreedm frm cardiac eents were ess in the TAR grup. Angigraph demnstrated SvGpatenc at arund 90%.28

The results of SVG patency may reect the importance of secondary preventative therapy.Sme studies hae nted an increased rate f stensis f radia arter grafts and haecautined n their appicabiit in target esses with n mderate stensis. Tta arteriarevascularisation may confer long term benet but application of the radial artery graft tosub-critical stenoses may not confer benet.29-3

D ptients undergoing surgic rescuristion o the et nterior descending coronrrter shoud receie n intern mmmr rter grt, here esibe.

4.2.6 CoST EFFECTIvENESS oF REvASCUlARISATIoN TECHNIQUESSeera studies hae cmpared the cst effectieness f CABG and PCI.32-42 The primar utcmein these studies was change in resurce use (initia cst f prcedure and future resurcesrequired, particuar thse assciated with reascuarisatin); the tpe and numbers f repeatreascuarisatin fwing the initia prcedure was the ke surce f ariabiit acrss

studies.

Athugh the studies hae different incusin and ecusin criteria and hae used differenttimeframes and csting techniques, the eidence suggests that CABG is the mre epensietechnology for the initial in-hospital stay and during the rst few years of follow up. Thereafter the need for repeat revascularisation erodes the initial cost advantage of PCI so that by veyears following any procedure the cost differences are unlikely to be signicant.

Carefu patient seectin can impre cst effectieness, with patients with tw esse diseasehaving signicantly lower cost long term (ve to eight years) for PCI than CABG; whilst CABGis mre cst effectie in patients with seere mutiesse disease.

on ne f these studies used drug euting stents40 and this imits the generaisabiit f theeidence t a setting which has a high utiisatin f such stents.

The seen cst effectieness studies cmparing cated stents with uncated stents40,43-48 shwedthat using cated stents was n cst effectie fr a minrit f patients wh were at high riskf an aderse eent such as thse with mutiesse disease r cmpe esins.





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4.3 pOST INTERvENTION DRUG THERapy

With the diagnsis f CvD, secndar preentin medicatin is mandatr and shud incudechester wering therap usua with a statin, antipateet therap and, if apprpriate,antihpertensie and hpgcaemic medicatins (see section 3.3 and SIGN guideline 97 on risk

estimation and the prevention of cardiovascular disease).

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Fwing CABG, aspirin (75-300mg dai) is the rutine prescribed antipateet medicatin.49 The administratin f aspirinwithin 48 hurs f CABG was assciated with a 48% reductin in MI and a 50% reductinin strke. The mrtait in thse receiing ear aspirin was .3% cmpared t 4% amngstthse wh did nt.50 The Sciet f Thracic Surgens has recmmended that aspirin shudbe stopped for three to ve days before elective CABG and then restarted early after surgery.5 In thse interant f aspirin, cpidgre (75 mg dai) shud be cnsidered.

No evidence was identied for the use of dual antiplatelet therapy following PCI in patientswith stabe angina. Fwing PCI, there is eidence t supprt the use f dai aspirin (75 mg)cmbined with cpidgre (75 mg) fr ne mnth in patients with acute crnar sndrme.one tria shwed that ng term administratin f cpidgre after PCI (mean ength eightmnths) was assciated with a wer rate f cardiascuar death, mcardia infarctin, r an

reascuarisatin (p=0.03), and f cardiascuar death r mcardia infarctin (p=0.047)cmpared t paceb.52 Dua therap is assciated with higher peratie beeding than singeantipateet therap.53 The American College of Cardiology (ACC)/American Heart Association(AHA) guideine n percutaneus crnar interentin suggests that fr cated stents theduratin f therap shud be etended up t si mnths depending n the stent used. 54

No evidence was identied for the use of long term beta blockers for asymptomatic patientsfwing CABG.

In a patients with eidence f eft entricuar impairment, ptima medica therap shudincude use f an ACE inhibitr (r angitensin II receptr bcker if interant) and cnsider the use f beta bckers and further renin-angitensin-adsterne bckade (see SIGN guideline95 on the management of chronic heart failure).48

4.4 pOST INTERvENTION REHaBIlITaTION

SIGN guideine 57, cardiac rehabiitatin, recmmends that patients wh hae undergnecrnar reascuarisatin shud receie cmprehensie rehabiitatin.55

4.5 EffECT Of ON-/Off-pUMp CORONaRy aRTERy BypaSS GRafTING ON

COGNITIvE IMpaIRMENT

The use f ff-pump surgica techniques deeped, in part, as a methd f reducing ptentiacgnitie impairment after surger (see section 6.3). A meta-anasis cmparing ff-pump withconventional on-pump CABG did not demonstrate any signicant differences in 30 day mortality,mcardia infarctin, strke r rena dsfunctin but did shw a reduced incidence f atria

brillation, transfusion, inotrope requirements with reduced length of ventilation time and intensivecare unit (ITU) and hspita sta. The resuts fr graft patenc and neurcgnitie functin wereincncusie.56 Two good quality RCTs were identied which indicate a benet of off-pumpsurger in reductin f cgnitie impairment at three mnths fr patients with ne t three essesbpassed, which is nt sustained at 2 mnths (decine 2% in ff-pump grup and 29% in n-pump grup at three mnths, 3% and 33% respectie at 2 mnths).57,58 one chrt studalso found a slight benet for off-pump surgery at six months in younger patients.59

A stud king at n- and ff-pump surgica grups with cardiac and heath cntrs fundno evidence of cognitive decline at three or 12 months on objective testing, but signicantbaseine differences between surgica and nn-surgica cntr grups in sef reprted cgnitieprbems. The stud cncudes that CABG patients, ike simiar patients with ng-standingcrnar arter disease, hae sme degree f cgnitie dsfunctin secndar t cerebrascuar

disease befre surger.60



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In contrast, one RCT found no signicant decline in cognitive function in either groupimmediate after surger and at tw and a haf mnths. 6

Several variables appear to inuence outcomes. Age did not predict decline in cognitive functionathugh the patients tended t be reatie ung (in their sities).62 Patients ma hae markedpre-surgical decits which mask the potential effect on cognitive function of type of surgery.6 Further eidence f the effect f CABG n cgnitie functin is reiewed in sectin 6.3.4.

a O-um coronr rter bss grting shoud not be used s the bsis o roidingong term rotection ginst cognitie decine.

4.6 MaNaGING RESTENOSIS

Restensis rates fwing uncated stenting hae been reduced, but nt eiminated, b theuse f cated stents.63 No evidence was identied on which to base recommendations on thetreatment f restensis, athugh bth CABG and PCI with cated stents ma be cnsidered.

4.7 MaNaGING REfRaCTORy aNGINaRefractory angina can be dened as persisting unsatisfactory control of anginal symptoms despitemaima terated medica therapies and withut further reascuarisatin ptins.

4.7. CoGNITIvE BEHAvIoUR AND REHABIlITATIvE APPRoACHES To MANAGEMENT

SIGN guideine 57 n cardiac rehabiitatin recmmends that patients with stabe angina shudbe referred fr rehabiitatin if the hae imiting smptms and after reascuarisatin.55 Patients presenting with refractr angina hae ften nt receied a cmprehensie rehabiitatinprgramme, which ma impre management f smptms. The initia treatment f thesepatients shud fw an educatina and rehabiitatie apprach, prgressing t a cgnitiebehaiur apprach where apprpriate. The atter has demnstrated psitie utcmes inbth angina and chrnic pain.64,65 These appraches shud be taken prir t cnsidering the

use f transcutaneus eectrica nere stimuatin (TENS), temprar smpathectm, use f piids, destructie smpathectm, and ther interentins such as spina crd stimuatin,(see section 4.7.2) surgica transmcardia reascuarisatin, (see section 4.7.3) and enhancedeterna cunterpusatin (see section 4.7.4).

D Patients with refractory angina may benet from an educational and rehabilitationroch bsed on cognitie behiour rincies rior to considering other insietretments.

4.7.2 SPINAl CoRD STIMUlATIoN

This methd cnsists f inserting a stimuating eectrde int the thracic epidura space under local anaesthetic with the nal position of the electrode being determined by the patient’s

sensatin f paraesthesia in the area where the angina pain is usua fet. one sma randmisedtria asting si weeks shwed a reductin in angina attacks (p=0.0).66 In this stud athughthe cntr grup had an inactie stimuatr it is nt pssibe t reme the bias f the ack f paraesthesia induced b the neurstimuatr.





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4.7.3 SURGICAl TRANSMyoCARDIAl REvASCUlARISATIoN

This prcedure cnsists f using a aser t create between 20-40 ne miimetre transmurachannes in the epsed eft entrice. Suggested effects are the prmtin f angigenesis,restring bd supp t the mcardium r destring its inneratin.

A meta-anasis f seen trias cmpared aser surgica transmcardia reascuarisatin (TMR)pus cntinuing maima medica therap with cntinuing medica therap ane in patientswith nging smptms but nt amenabe t reascuarisatin interentin. oera, there wasa non-signicant reduction in survival after one year with TMR (odds ratio; OR, 1.17, 95% CI0.74 to 1.83, p=0.75), although angina class improvement was signicantly better with TMR(OR 0.10, 95% CI 0.06 to 0.17, p<0.0001).67 In this tpe f tria with the ack f a shamprcedure there is a buit in bias twards a paceb effect and masking is impssibe.

one tria, based in the UK, shwed a decrease f CCS scre fr angina f at east tw cassesin 25% f thse receiing the prcedure as ppsed t 4% f patients receiing medicamanagement alone at 12 months (p<0.001). The operative risks need to be balanced againstthe potential benets of moderate improvement in angina and only minimal improvement ineercise capacit (p=0.52).68

4.7.4 ENHANCED ExTERNAl CoUNTERPUlSATIoN

Enhanced eterna cunterpusatin (EECP) ines the use f cmpressed air appied ia cuffst the patient’s wer etremities in snchrn with the cardiac cce. In ear diaste, pressureis appied sequentia frm the wer egs t the wer and upper thighs t prpe bd backt the heart. This resuts in an increase f arteria bd pressure and retrgrade artic bdow during diastole (diastolic augmentation). At end-diastole, air is released instantaneouslyfrm a the cuffs t reme the eterna appied pressure, awing the cmpressed essest recnfrm, thereb reducing ascuar impedance.

one RCT shwed that when cmparing EECP and paceb, eercise duratin increased in bthgroups, but the between-group difference was not signicant (p>0.3).69 Time to ≥1-mm ST-

segment depression increased signicantly from baseline in EECP compared with placebo(p=0.0). Mre EECP patients reprted a decrease and fewer eperienced an increase inangina episodes as compared with placebo patients (p<0.05). Glyceryl trinitrate usagedecreased in EECP but did nt change in the paceb grup. The between-grup differencewas not signicant (p>0.7).



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5 Stbe ngin nd non-crdic surger

Patients with crnar heart disease underging nn-cardiac surger are at increased risk f aderse cardiac eents.70 Periperatie cnditins such as stress, tachcardia, hpaemia,hptensin, hpertensin, anaemia, hpthermia, acute pain and hpercaguabe statescan a affect the mcardium and crnar micrcircuatin and ma precipitate mcardiainfarction, myocardial ischaemia or signicant arrhythmias. These cardiac events are associatedwith increased mrtait and mrbidit, ength f sta and cnsequent higher csts. Preentinf periperatie cardiac cmpicatins is cnsidered a pririt and has been the subject f practice guideines.7 Patients wh deep pstperatie ischaemic eents such as mcardiainfarctin r ischaemia are at increased risk f deeping aderse cardiac utcmes withintw ears fwing surger.72

5.1 aSSESSMENT pRIOR TO SURGERy

An assessment f the risk f serius cardiac cmpicatins requires teamwrk and gd

communication between surgeons, anaesthetists and physicians/cardiologists. This maybe faciitated b preperatie cinics. Assessment fr surger shud cnsider the inherentprocedural risk, patient-specic factors and functional capacity. As myocardial ischaemia is animprtant predictr f majr aderse cardiac eents after nn-cardiac surger, a fu cinicahistr and eaminatin and resting eectrcardigram shud be assessed.7 Patients atincreased risk may undergo additional risk stratication usually by exercise tolerance test.7 Where this is impractica ther nn-inasie tests such as stress echcardigraph r mcardiaperfusin scintigraph cud be cnsidered. Crnar angigraph ma be indicated where ahigh risk is identied and is the investigation of choice to dene the coronary anatomy.

Other patient-specic factors are listed in Table 2. The ACC/AHA guidelines on perioperativecardiascuar eauatin fr nn-cardiac surger incude a fu discussin f preperatie

assessment.7

Table 2: Clinical predictors of major perioperative cardiovascular risk

Patient-specic risk factors

Acute r recent mcardia infarctin *

Unstabe r seere angina

Decmpensated heart faiure

Signicant arrhythmias

Seere auar heart disease

Adapted from American Heart Association/American College of Cardiology guidelines7

* Acute myocardial infarction is dened as occurring within seven days of surgery and recentinfarctin ccurring between seen das and ne mnth f surger.

If a recent stress test des nt indicate residua mcardium is at risk, the ikeihd f reinfarctinis low and although no adequate clinical trials have been identied it seems reasonable to waitfur t si weeks after MI t perfrm eectie surger. Histrica recmmendatins t wait simnths after MI befre eectie surger are unsupprted b eidence and the majr determinantf risk is the amunt f residua at-risk mcardium. 7,73

5 STaBlE aNGINa aND NON-CaRDIaC SURGERy




5.. RISK SCoRING SySTEMS

The discer f majr risk factrs befre nn-cardiac surger wi usua resut in pstpnementf surger and the inestigatin and treatment f that prbem. Prcedura risk shud as bequantied (see Table 3), to help select patients who may benet from further evaluation or inestigatin.

Table 3: Surgical procedures stratied by cardiac risk level

HIGH RISK pROCEDURES reported cardiac risk >5%

Emergenc majr peratins, particuar in the eder

Artic and ther majr ascuar surger

Periphera ascuar surger

Anticipated prolonged surgical procedures associated with large uid shifts and/or blood loss

INTERMEDIaTE RISK pROCEDURES reported cardiac risk generally <5%

Cartid endarterectm

Head and neck surger

Intraperitnea and intrathracic surger

orthpaedic surger

Prstate surger

lOw RISK pROCEDURES reported cardiac risk generally<1%

Endscpic prcedures

Supercial procedures

Cataract surger

Breast surger



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The Revised Cardiac Risk Index (RCRI) is a simple risk stratication tool which combines patientrisk and prcedura risk and can aid cinica decisin making (see Table 4).70 In this reprt f the risk f majr cardiac cmpicatins with majr nn-emergenc, nn-cardiac surger, sifactors with approximately equal prognostic importance were identied.

Table 4: Revised Cardiac Risk Index

Cinic ctors

High risk surger

Histr f ischaemic heart disease

Histr f cngestie heart faiure

Histr f cerebrascuar disease

Preperatie insuin treatment

Preoperative creatinine >180 micromol/l.

The rates f majr cardiac cmpicatins pstperatie with 0, , 2, 3 r mre risk factrs were0.5%, .3%, 4% and 9% respectie.

High risk surgery is dened as intraperitoneal, intrathoracic, or suprainguinal vascular procedures.A history of CHD is dened as any of the following: a history of MI, positive exercise tolerancetest, current cmpaint f chest pain f ischaemic rigin, use f nitrate therap r pathgicaQ waves on ECG. Patients with prior revascularisation are only classied as having CHD if theyhae ne f the abe criteria.

Patients identied at high risk of cardiac complications using the RCRI may undergo further riskstratication with non-invasive testing or other risk reduction management strategies. These riskreductin strategies ma ine preperatie reascuarisatin r medica therap.74 Thse

identied as low risk may proceed to surgery. The Revised Cardiac Risk Index has been modiedfr patients haing ascuar surger.75

The urgenc f the surgica prcedure and the presence f recent cardiac inestigatins wiinuence the decision on whether further cardiac investigations are appropriate. Clinicalcircumstances wi determine whether a dea fr inestigatin and preperatie ptimisatincan be justied.

Additina infrmatin can be deried frm the functina capacit f patients and nn-inasietests such as eercise ECG terance testing, stress echcardigraph and MPS. In genera,indicatins fr preperatie crnar angigraph are simiar t the nn-peratie setting.These are patients with knwn r suspected CHD and:

eidence f high risk f aderse utcme based n nn-inasie test resuts, r

unstabe angina facing intermediate r majr tpes f nn-cardiac surger, r

equica nn-inasie test resuts in a patient with high cinica risk underging high risknn-cardiac surger.7





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The risk of cardiac complications is signicant (4% or greater) in patients undergoing high risksurger and wh hae at east ne CHD risk factr (see Table 4). These indiiduas shudgenera be cnsidered fr further inestigatin. Sme cmbinatins f risk factrs ma ntpredispse the indiidua t equa ees f risk fr cardiac cmpicatins and cinica judgementshud be used t stratif patients accrding.

B As part of the routine assessment of tness for non-cardiac surgery, a risk assessmenttoo shoud be used to unti the risk o serious crdic eents in tients ithcoronr hert disese.

B ptients undergoing high risk surger ho he histor o coronr hert disese,stroke, dibetes, hert iure or ren dsunction shoud he urther inestigtion beither exercise toernce testing or other non-insie testing or coronr ngiogrh,i rorite.

Where a high risk is identied, a strategy for risk reduction should be agreed. This willrequire teamwork and good communication between surgeon, anaesthetist, physician/ cardigist and patient.

5..2 FUNCTIoNAl CAPACITy

Functina capacit has been shwn t predict periperatie and ng term cardiac eentsand shud be part f the preperatie assessment f patients with CHD underging majr surger.8,82

Functina capacit can be epressed in metabic equiaents f task (METs). one MET is theoxygen consumption of a 40 year old 70 kg man at rest and is equal to 3.5 ml/min/kg. Patientswh are unabe t meet a fur MET demand during mst nrma dai actiities are at increasedrisk f periperatie and ng term cardiac eents.76

Different scring sstems are aaiabe t measure functina capacit bjectie such asthe NyHA Scre,77 Karnfsk Perfrmance Scae78 r the Duke Actiit Scre which is asef cmpeted questinnaire using a set f cmmn dai iing items.79 Simpe eercisetesting may further rene risk assessment. The failure to climb two ights of stairs, which is theequivalent of > four METs, is a good predictor of mortality associated with thoracic surgeryand cmpicatins after majr nn-cardiac surger.80

Cardipumnar eercise testing has been used t identif high risk grups fr majr nn-cardiac surger. The measurement f anaerbic threshd (AT) ma be a better predictr than themaimum gen cnsumptin (vo

2ma) as it is mre independent f patient mtiatin.8,82

In eder patients underging majr abdmina surger, a grup f patients with an AT f <11 ml/kg/min (three METs) had a higher mortality rate when compared to the group withan AT >11 ml/kg/min. The anaerobic threshold is a better measure of the ability to meet thedemands f prnged stress assciated with majr surger than vo

2ma. The anaerbic

threshd ma ar in an indiidua between 50% t 00% f the vo 2 ma.Further studies are necessar t eauate the cst effectieness and cinica utiit f cardipumnar eercise testing as a means f risk assessment befre majr surger. Simpeassessment f functina capacit b patient questinnaires and simpe eercise testing suchas stair cimbing in thracic surger are auabe.79,80 Man hspitas in Sctand d nt haeaccess t cardipumnar eercise testing.

D an objectie ssessment o unction ccit shoud be mde s rt o thereoertie ssessment o tients ith coronr hert disese beore mjorsurger.



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5.2 pREOpERaTIvE REvaSCUlaRISaTION

Data from the Coronary Artery Surgery Study (CASS) registry conrmed that clinically stablepatients (n=,297) underging w risk surger (urg, rthpaedic, breast, and skinsurgery) had a low mortality (<1%) regardless of prior coronary treatment.83 Thse (n=,96)

underging high risk surger (abdmina, ascuar, thracic and head and neck surger) had acombined MI/death rate among patients with non-revascularised CHD of >4%. Among theseprir CABG was assciated with fewer deaths (.7% s 3.3%) and mcardia infarctins (0.8%s 2.7%) cmpared t medica managed crnar disease. These patients were enredbetween 974 and 979 and the resuts ma nt be appicabe t cntemprar practice.

The Crnar Arter Reascuarisatin Tria randm assigned patients at risk fr periperatiecardiac cmpicatins and cinica significant crnar heart disease t underg either reascuarisatin r n reascuarisatin befre eectie majr nn-cardiac ascuar surger.84 At2.7 ears after randmisatin, mrtait was 22% in the reascuarisatin grup and 23% in theno revascularisation group. These results conict with the CASS study and may reect the biasf bseratina studies r that majr ascuar surger is high risk and that adances in medicineresuted in man f the patients in the n reascuarisatin grup receiing beta bckers, statins,

aspirin and ACE inhibitors. After coronary catheterisation patients with signicant left main stenosis(54 patients), pr eft entricuar functin ( patients) and seere artic stensis (eight patients) wereecuded frm this stud. on 3% f the n reascuarisatin grup had tripe esse disease.

Preperatie CABG wi be apprpriate fr n a minrit f patients as the prcedure carries asignicant risk of mortality (around 3%) and morbidity, and these risks must be added to thosef the crnar angigraph and the nn-cardiac surger itsef. Cmpared t case-matchedcntrs, patients wh underwent nn-cardiac ascuar surger within a mnth f CABG sufferedsignicantly greater mortality (20.6% vs 3.9%, p<0.005).85 A signicantly higher risk of cardiaccomplications (27%) was found in patients undergoing non-cardiac procedures in the rst monthafter CABG.86 This remained higher (7%) unti the sith mnth fwing CABG.

Although denitive evidence for a safe period to delay non-cardiac surgery after CABG is lacking,it seems prudent t aid eectie nn-cardiac surger fr at east ne mnth and pssib up

to six months. The timing of surgery will depend on the balance of risks and benets which, inan indiidua patient, wi depend n the seerit f the crnar arter disease and the natureand urgenc f the nn-cardiac surger.

Overall survival benet is seen only in patients who would warrant CABG surgery independentlyof their major non-cardiac surgery. These indications are signicant left main stenosis, tripleesse disease in cnjunctin with lv dsfunctin, tw esse disease incuding prima lAD,and unstabe smptmatic CHD despite fu medica therap.87 When time aws these patientsma be ffered preperatie CABG.

There is n eidence fr the use f prphactic percutaneus crnar interentin befrenn-cardiac surger in patients with stabe angina.

In the absence f an ther data, indicatins fr PCI are essentia identica t the nn-peratie

setting, which are the reief f angina smptms resistant t medica therap. Patients whhae had PCI and stent insertin are at risk f stent thrmbsis if their dua antipateet therapis discntinued.88,89 The risk f cardiac cmpicatins after nn-cardiac surger is greater if arecent (<35 days) coronary artery stent has been inserted compared to >90 days. 90

The cmbinatin f aspirin and cpidgre increases the risk f beeding during CABG, whichma as be increased pstperatie.9,92

There is imited eidence regarding the best time dea after PCI befre prceeding t nn-cardiacsurger. Fwing ban angipast, at east ne week shud be eft t aw heaing f thetraumatised esse wa. After a bare meta stent insertin, fur weeks f dua antipateet therapare required. A dea f si weeks befre nn-cardiac surger has been recmmended b whichtime bare meta stents are genera re-endtheised and cpidgre can be discntinued.88,89

Drug euting stents dea re-endtheiaisatin and dua antipateet therap (aspirin puscpidgre) must be cntinued fr at east three mnths after sirimus stents and si mnthsafter pacitae stents.93,94 Thereafter, cpidgre can be discntinued.




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The DECREASE tria studied 2 high risk patients with psitie resuts f dbutamine stressechcardigraph underging ascuar surger.20 Thse receiing bispr at east ne weekpreperatie and cntinued fr 30 das after surger had a reductin f 90% in the primarendpint f death frm cardiac causes r nn-fata mcardia infarctin which ccurred intw patients in the bispr grup (3.4%) and 8 patients in the standard care grup (34%,

p<0.001). Another RCT found that atenolol administered intravenously 30 minutes beforesurger and ra thereafter in high risk mae patients reduced ischaemia but nt cardiac deathrisk r MI during hspitaisatin but did impre suria up t tw ears after discharge. 202

Anther sma RCT in patients underging ascuar surger shwed that intraenus esminfusin frm surgica recer fr 48 hurs reduced the incidence f ischaemia. Ischaemiapersisted in the postoperative period in eight of 11 patients taking placebo (73%), but only veof 15 patients taking esmolol (33%, p<0.05).203

In summar, seera RCTs and ne meta-anasis hae demnstrated that beta bckers reducethe incidence f intraperatie mcardia ischaemia and in high risk grups ma reduce the riskf aderse cardiac eents such as mcardia infarctin and cardiac death after surger. Thereis still a debate in the literature regarding which patients will benet from beta blockade and

n the ptima methd f administratin. The withdrawa f beta bcker therap is assciatedwith increased risk. A arge internatina stud which addresses the periperatie use f betabckers is underwa.

In a retrspectie reiew f 782,969 patients beta bcker treatment was assciated withsignicant reductions in mortality in the highest risk patients (RCRI score of three or greater)but was of no benet among the lowest risk categories (those with a score of zero or one). 204

Genera, if time aws, it wud seem safer t intrduce the beta bcker in adance andaw time fr dse titratin and assessment f terance. Acute withdrawa f beta bckers inthe pstperatie perid ma increase the risk f pstperatie cardiac cmpicatins. 205

SIGN guideine 77 n pstperatie management in aduts206 and the American Cege f Cardiology/American Heart Association guideline on perioperative beta blocker therapy207

recmmend cntinuatin f estabished beta bckade in patients underging surger.a preoertie bet bocker ther shoud be considered in tients ith coronr hert

disese undergoing high or intermedite risk non-crdic surger ho re t high risko crdic eents.

Where pssibe beta bckers shud be started das r weeks in adance f surger taw fr dse titratin and t assess terance.

B pre-existing bet bocker ther shoud be continued in the erioertie eriod.

5.3.2 AlPHA 2 AGoNISTS

Alpha 2 agonists inhibit the sympathetic outow, reduce peripheral noradrenaline release anddilate post stenotic coronary arteries and may be benecial in the perioperative setting. Onemeta-analysis identied 23 studies comprising 3,395 patients. Alpha 2 agonists signicantlyreduced mrtait (RR 0.47; 95% CI 0.25 t 0.90; ARR .9%; p=0.02) and mcardia infarctin(RR = 0.66; 95% CI 0.46 t 0.94; ARR 3.3%; p=0.02) after ascuar surger. 208 The argestbenets were seen in vascular and cardiac surgery. Non-signicant increases in bradycardiaand hypotension were also seen. Minimal data was identied on the use of alpha 2 agonistsin nn-ascuar surger. There has been n direct cmparisn f apha 2 agnists with betabckers. Further arge RCTs are needed in nn-cardiac surgica patients.

In a stud f 2,854 patients with r at risk f crnar heart disease miazer administeredduring anaesthesia and surger n a double blind placebo controlled basis led to a signicant

reductin in a cause and cardiac mrtait (RR=0.67, CI 0.45 t -0.98; ARR 4.3%) in patients

underging

majr recnstructie ascuar surger.209





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Miazer and demedetmidine are nt icensed in the UK. Cnidine is aaiabe and athughthe potential benets do seem to be a class effect, the data on clonidine are limited to smaller studies.

one RCT f 90 patients with r at risk f CHD inestigated the effect f cnidine in patientsunderging nn-cardiac surger. The stud grup was gien 0.2 mg ra cnidine fwedb a patch fr fur das. Prphactic administratin f cnidine reduced the pstperatiemrtait fr up t tw ears (RR 0.43, CI 0.2 t 0.89; ARR 4%; p=0.035).20 Cnidine isnt icensed fr this indicatin.

5.3.3 CAlCIUM CHANNEl BloCKERS

There is sme eidence that CCBs ma reduce the cardiac risk f nn-cardiac surger. Theeidence base is weak, cnsisting f sma, ften unbinded studies. one meta anasis incuded studies f ,007 patients in which ditiazem, erapami r nifedipine were assessed in majr nn-cardiac surger.2 Cacium channe bckers reduced b haf periperatie ischaemia(RR 0.49, CI 0.30 t 0.80; p=0.004) and supraentricuar tacharrhthmia (RR 0.52, CI 0.37to 0.72; p<0.0001). There was no effect on heart failure. Trends toward a reduction in MI

(RR 0.25, CI 0.05 t .8) r mrtait (RR 0.4, CI 0.4 t .6) were seen. Pst hc anasesshowed a signicant reduction in death/MI (RR 0.35, CI 0.15 to 0.86; p=0.02). The majorityf these effects were attributabe t ditiazem. Further arge we designed studies are requiredto conrm any benet. There are no comparative studies with other drugs.

A meta-anasis f RCTs fr the preentin f cardiascuar cmpicatins f nn-cardiacsurgery found no benet for the use of perioperative CCB on cardiac death. 99

Further eidence is required befre CCB can be recmmended as a frm f medica therapt reduce the cardiac risk f nn-cardiac surger.

5.3.4 ANTIPlATElET THERAPy

Aspirin has both antiplatelet and anti-inammatory effects and is known to reduce mortality in

unstabe angina and after MI and strke. Mst patients with stabe angina wi be prescribedw-dse aspirin therap fr secndar cardiascuar preentin.

In ve RCTs, preoperative administration of aspirin resulted in increased blood loss, bloodtransfusin and reperatin after cardiac surger.22-26

The benets of aspirin administration before or after non-cardiac surgery are less well dened.SIGN guideine 62 n prphais f enus thrmbembism recmmends pre- andpstperatie aspirin as prphais f asmptmatic and smptmatic enus thrmbembism(vTE) in surgica patients.27

Aspirin may be stopped ve days before major non-cardiac surgery because of the bleedingrisks but these must be baanced against the risk f pstperatie thrmbtic cmpicatins suchas vTE, MI and strke. A meta-anasis shwed that whist the rate f beeding cmpicatins

was increased b w-dse aspirin b a factr f .5, it did nt ead t a higher seerit f beeding cmpicatins (with the eceptin f intracrania surger and pssib transurethraprstatectm) nr f periperatie mrtait because f beeding cmpicatins.28

There is eidence that w-dse aspirin reduces the risks f strke assciated with cartidendarterectm and shud be cntinued preperatie.29 The American Assciatin f Ceges f Pharmac recmmends aspirin in patients receiing prsthetic femrpppiteabpass grafts with therap starting preperatie.220

C lo-dose sirin ther shoud on be ithhed beore non-crdic surger intients ith coronr hert disese here the sirin reted beeding comictionsare expected to be signicant (VTE, MI, stroke, peripheral vascular occlusion, or cardiovascular death).

D I o-dose sirin ther is ithdrn beore non-crdic surger in tients ithcoronr hert disese, it shoud be recommenced s soon s ossibe ter surger.



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5.3.5 NITRATES AND PoTASSIUM CHANNEl ACTIvAToRS

Gcer trinitrate infusins d nt reduce periperatie ischaemia22 and a sstematic reiewconcluded that there was insufcient evidence to support the use of nitrates in the perioperativeperid.99 No evidence was identied on nicorandil use in this setting.

5.3.6 STATINS

In the operative setting statins may inuence plaque instability and rupture and subsequentthrmbsis and crnar arter ccusin. one RCT f 00 patients underging ascuar surgershwed that 20 mg f simastatin administered dai fr 45 das reduced the incidence f cardiac eents (RR 0.3; ARR 8%).222 obseratina studies hae shwn assciatins betweenstatin use and reduced cardiac eents after nn-cardiac surger.223,224

Ear cncerns abut the use and safet f statins during hspitaisatin fr majr surger haenot been conrmed.225 In a stud f 98 patients underging nn-cardiac surger, periperatiestatin use was nt assciated with an increased risk f mpath (ie creatine phsphkinaseeeatin with r withut musce cmpaints after majr ascuar surger). 226

B ptients ith coronr hert disese undergoing mjor non-crdic scur surgershoud be estbished on sttin beore surger.

Patients presenting fr nn-cardiac surger n statin therap shud hae the statincntinued thrugh the periperatie perid.

5.4 aDJUNCTIvE aNaESTHETIC TECHNIqUES

5.4. FACToRS ASSoCIATED WITH ISCHAEMIA

Mcardia ischaemia is assciated with hpia, hpthermia, anaemia, hpaemia,unstabe haemdnamics and inadequate pain cntr. These factrs ma aderse affectthe oxygen supply/demand relationship in the myocardium and must be considered in anypreentatie strateg (see SIGN guideline 77 on postoperative management in adults).206

5.4.2 EPIDURAl ANAlGESIA

one sstematic reiew f randmised trias f epidura anaesthesia indicated that the incidencef mcardia infarctin was reduced b abut ne third with neuraia bckade (oR 0.70,95% CI 0.54 t 0.90; ARR 0.9%; p=0.006).227 A smaer tria shwed that mcardia ischaemiawas reduced with epidura infusins after hip fracture surger.228

The MASTER stud did nt shw an imprement in utcmes after abdmina surger withepidura anagesia.229

5.4.3 INTRA-AoRTIC BAllooN PUMP IN NoN-CARDIAC SURGERy

The use f an intra-artic ban pump (IABP) has an estabished pace in the management f acute crnar sndrmes cmpicated b cardigenic shck, mcardia infarctin cmpicatedb entricuar septa defects r papiar musce rupture and refractr mcardia ischaemiaprir t reascuarisatin (see SIGN guideline 93 on acute coronary syndromes).

No RCTs were identied on the use of IABP in non-cardiac surgery. Case reports have suggestedthat some patients with severe CHD requiring urgent non-cardiac surgery may benet fromthe supprt f an IABP.55 Eperience in the insertin f and the management f the IABP is anessentia prerequisite t safe use.





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6 pschoogic nd cognitie issues

Psychological factors exert an inuence on patients with angina in several ways:

limitations and concerns related to living with angina can inuence mood, degree of disabiit, quait f ife and mrtait230-232

beliefs and misconceptions about heart disease have been shown to inuence outcome(see SIGN guideline 57 on cardiac rehabilitation, section 2.1.4), and eiciting and reframingunhepfu beiefs decreases disabiit 55,233

depression and anxiety inuence health service use (see SIGN guideline 57 on cardiacrehabilitation, sections 2.1.1 and 2.1.2 )55

the presence of depression inuences mortality and morbidity234-238

patients commonly report cognitive difculties following CABG60,26

This sectin addresses the eidence abut these issues.

6.1 HOw DOES aNGINa affECT qUalITy Of lIfE?The impact f angina n pschgica heath and functin can be measured b assessing mdand quait f ife (Ql) using aidated measures such as Hspita Aniet and DepressinScae (HAD). The eidence reiewed indicates a cnsiderabe impact f angina n Ql status.Depressin was assciated with prer functin.230,239-242

Tw arge Scandinaian sures f quait f ife using the questinnaires SF-36 and Swed-Quafound that patients with mild and moderate angina have signicantly lower quality of life ratingscmpared with the genera ppuatin and thse with diabetes, epieps, and asthma.230,232

The same stud grup as demnstrated reduced and impaired seua functining in anginapatients cmpared with nrma ppuatin.243

Tw studies cmparing patients with angina wh were awaiting reascuarisatin with the nrma

ppuatin fund imitatins in quait f ife cmpared with the genera Swedish ppuatin na dmains f Swed-Qua, and SF-36. Persistence f angina after interentin (fur ear fwup) was assciated with reduced Ql.244,245 A arge scae we cnducted stud f ,025 patientswith CHD and angina, ked at the assciatin between depressin, phsica imitatins andQl er a three mnth perid. Twent eight per cent f patients were depressed, which wassignicantly associated with poorer scores on the Seattle Angina questionnaire (p<0.001). Atthree mnth fw up, depressin was assciated with deteriratin f functina status. 230

A sma, we cnducted stud based in Sctand fwed up patients frm a chest pain sericefr si mnths. Standardised measures demnstrated presence f signicant symptoms of angina(58%) and breathessness (72%), with mre than haf affected b tiredness, mbiit prbemsand a restricted scia and dmestic ife. Mre than 75% f patients had aniet and depressinabe the nrma range, with risk factrs pr cntred.8

D ptients ith ngin shoud be ssessed or the imct o ngin on mood, uit oie nd unction, to monitor rogress nd inorm tretment decisions.

Md, quait f ife and functin in angina patients can be assessed using aidatedmeasures such as:

SF-36

Hspita Aniet and Depressin Scae (generic)

The Dartmuth Primar Care C-peratie Infrmatin Prject Functina HeathAssessment Chart

Seatte Angina Questinnaire – UK ersin

Cardiovascular Limitations and Symptoms prole (CHD specic).



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Quait utcmes framewrk (QoF) targets fr 2006 incude tw screening questins fr depression in patients with CHD for whom case nding has been undertaken in the previous5 mnths:

“During the ast mnth, hae u ften been bthered b feeing dwn, depressed r hpeess?”

“During the ast mnth, hae u ften been bthered b haing itte interest r peasurein ding things?”

6.2 IMpROvING SyMpTOM CONTROl wITH BEHavIOURal INTERvENTIONS

A systematic review of four RCTs reported that the evidence of efcacy of psychoeducationalinterentin fr the management f chrnic stabe angina was incncusie. Indiidua, thetrias indicated sme psitie effects n angina smptms, angina smptm-reated distress andphsica functining, hweer the used different utcme measures, timing f utcmes andhetergeneus anases f measures.246

An RCT eauating the use f the Angina Pan deiered b a nurse in primar care (patient hed

wrkbk and reaatin prgramme) t patients wh had begun treatment fr angina withinthe preceding 12 months, showed signicant reduction in mean number of self reported anginaattacks and physical limitation with reduction in anxiety and depression (p < 0.05). 247

one RCT f autgenic reaatin training (guided reaatin fcused n smatic sensatins)after angioplasty found that it reduced anxiety at two and ve months, although high drop-outsreduce the strength f this stud.248

B ptients ith stbe ngin hose smtoms remin uncontroed or ho reexeriencing reduced hsic unctioning desite otim medic ther shoud beconsidered or the angin pn.

An pscheducatina treatments which are shwn t reduce distress shud be

cnsidered angside interentina treatments.

6.3 THE EffECT Of TREaTMENT fOR aNGINa ON COGNITION

Patients’ reprts f cgnitie prbems fwing CABG are cmmn.60 The guideine has ntked at the eidence fr the mechanisms b which impairment ma ccur, apart frm ff- andn-pump prcedures (see section 4.5) and hpthermia (see section 6.3.3). Nr has it kedat eidence fr whether majr surger ther than CABG affects cgnitie impairment, nr thepreaence f cgnitie impairment in a CHD ppuatin as a whe.

6.3. DEFINITIoN oF CoGNITIvE DEClINE

An international consensus agreement denes cognitive decline as a 20% decrease in 20% of

tests.249

This denition allows comparison between studies but may produce a high proportionof false positives due to natural uctuations in performance during repeated testing.250 Afurther cnsideratin is whether bjectie eidence f cgnitie decine crreates with patientperceptin f decine.

outcmes frm different studies are nt awas cmparabe as nt a studies empneurpschgica measures cnsistent with the cnsensus agreement, there are differing timeperiods for follow up and difculties controlling for other factors that might inuence outcomes,eg age, pre-mrbid ees f impairment and ther ariabes.

6.3.2 PERCUTANEoUS CoRoNARy INTERvENTIoN

There is itte eidence n the effect f PCI n cgnitie functin. one underpwered studcmpared PCI with CABG and fund n difference in cgnitie functin at si r 2 mnthsin either treatment.25

6 pSyCHOlOGICal aND COGNITIvE ISSUES




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A further stud with pr methdg assessed patient and spuse perceptin f memrprbems ne t tw ears pst CABG and angipast. This fund n difference betweenCABG and PTCA patients.252

6.3.3 CoRoNARy ARTERy ByPASS GRAFTING

Medical factors

Hpthermia during CABG des nt affect cgnitie functin pstperatie r at three mnthfollow up. Use of hypothermia showed a non-signicant trend to reduction of non-fatal strokes(oR 0.68, 95% CI 0.43-.05).253

one bseratina stud fund n reatinship between the increase in esins fund n MRIscan pst CABG and increase in cgnitie decine.254

Patterns of cognitive decline

The degree f decine aries depending n the ength f time since surger. Cgnitie decineis reatie cmmn in the ear perid fwing surger and, in sme patients, the initiadecline may improve over the rst three months. A systematic review of 12 cohort studies and

interentin studies fund that 22% f patients had eidence f cgnitie decine at twmnths pst CABG. The reatie ear fw up perid used ma erestimate the nger term seerit f the prbem.255

Papers published subsequent to this review describe conicting results for decline in later timeperids pst surger. Tw rbust ngitudina studies f cgnitie decine pst CABG funddecine at si mnths in 24% and in 39% f thse with pre-surgica impairment. 256,257 Thispattern was as fund b tw ess rbust studies. 258,259

lnger term fw up f patients indicates an increase in the preaence f decine frm 24%at six months to 42% at ve years,256 with simiar resuts frm anther stud.260 The octpusstud grup fund an increase in decine in bth n- and ff-pump surgica grups frm sit 2 mnths (2-33% in ff-pump grup, 29% t 33% in n-pump grup). 57 These ndings

indicate that other factors may inuence continuing decline related to presence of cardiovascular disease and the ageing prcess.

B ptients undergoing coronr rter bss grting shoud be dised tht cognitiedecline is relatively common in the rst two months after surgery.

A rbust chrt stud cmpared n-pump and ff-pump surgica patients, CHD patients withutsurger and ‘heart heath’ cntrs t tr t cntr fr the presence f cardiascuar andcerebrascuar disease.60 Bth bjectie and subjectie cmpaints f cgnitie decine er 2 mnths were assessed. A three cardiac grups had wer cgnitie scres at baseine (befresurger), indicating sme degree f impairment reated t CHD status. A fur grups shwedimprement in functin er 2 mnth fw up with n eidence that surgica patientsdid ess we than cardiac cntrs. Subjectie reprts f deteriratin in memr, persnait

and reading were signicantly more frequent in both surgical groups compared with controls. Surgery appears to exert a signicant inuence on patient perception of decline. Although thissef reprt is reated t presence f depressin, md did nt epain the higher incidence inthe surgical groups. These results conict with other studies and indicate that use of appropriatecntrs ma prduce a different pattern f eidence f decine.

A further stud fund that 37% f patients shwed a decine in cgnitie functin n frmatesting at si weeks pst CABG but this did nt crreate with patient perceptin f cgnitiedifculties.26



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The fwing factrs predict pr cgnitie utcme:

age256,257,259

eidence f decine preperatie and at discharge256,257,259

fewer ears f educatin256,258,259

aniet and depressin257,26

femae gender 259

hpertensin259

nn-crnar atherscersis258,259

chrnic disabing neurgica iness258

imited scia supprt.258

A chrt stud ked at cgnitie impairment and driing perfrmance pst CABG andangipast (fur t si weeks). Perfrmance was wrst in pst CABG grup (48% s 0% f paitents shwing cgnitie impairment) but ack f ng term fw up means resuts shudbe iewed with cautin.262

A single study with a small sample indicated potential benet of pre CABG treatment with

hperbaric gen in reducing neurpschgica dsfunctin. lack f aaiabiit f faciitieswi imit aaiabiit f this treatment.263

D ptients ho re oder nd he other eidence o theroscerosis nd/or existing cognitieimirment m be more t risk o incresing decine nd these ctors shoud beconsidered hen euting otions or rescuristion to chiee smtom reie.

6.3.4 EFFECT oF MEDICATIoN oN PSyCHoloGICAl FACToRS

Patients ften reprt perceied changes in pschgica functining whie taking cardiacmedicatins. There is er imited eidence aaiabe t address this questin. An RCT cmparingastatin with paceb in heath unteers fund n effect n measures f menta heathand incncusie minr reductins in cgnitie functin (NB astatin is nt icensed in the

UK).264 An RCT cmparing sartan with aten in eder patients with hpertensin indicatedsome minor benet of losartan in improving immediate and delayed memory (p<0.05).Hweer, sma numbers and the nn-standard utcme measures used mean these resutsare incncusie.265

There is n rbust eidence in patients with angina demnstrating an effect f medicatin npschgica functining.

6.4 THE EffECT Of pSyCHOlOGICal faCTORS ON ClINICal OUTCOMES

INClUDING MORTalITy

Depressin in pst MI patients predicts mrtait and mrbidit55 and pschgica distress isassciated with higher heathcare csts.266 Eidence reiewed esewhere (see SIGN guideline

97 on risk estimation and the prevention of cardiovascular disease),73 indicates that depressinis as a primar risk factr fr the deepment f CHD f simiar magnitude t standard riskfactrs. The pattern in patients after CABG is simiar, indicating that depressin shud be treatedwith the same imprtance as ther risk factrs. A reiew f depressin in CHD indicates theneed t address this prbem sstematica, and describes ptentia screening measures. 267

6.4. ANxIETy AND DEPRESSIoN

Depression is a signicant factor inuencing mortality and morbidity post CABG. The prevalencef depressin befre surger ranged frm 0% t 43%,234-238,268,269 and persisted at ne ear inup t 2% f patients.234 Aniet and depressin were assessed using aidated measures, withclassication of anxiety and depression being determined by scoring above a certain cut-off pint (cinica caseness) n the standardised measure f pschiatric adjustment used.





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Three studies234-236 eamined the reatinship between depressin and mrtait incuding nearge rbust stud with ng fw up (n= 87, mean fw up 5.2 ears).234 Mderate tseere depressin pre CABG r persistent depressin up t si mnths was assciated withtw- t threefd increase in risk f death.

Anther stud shwed highest fear and aniet preaence just after being put n the CABGwaiting ist (50%) with ees cear drpping at admissin (30%) and cntinuing t drpsight at three mnths after surger (20%). Differing aniet measures gae different rates.Thse under 55 ears remained mre fearfu.270 Wmen were mre anius and depressedpreperatie than men 234,270-272 and ne stud indicated that wmen iing ane were mredistressed than thse iing with partners.270

one stud shws high rates f aniet and depressin pre CABG (aniet 55%, depressin32%) which reduced t 32% and 26% three mnths after CABG. High ees preperatiepredicted high ees three mnths after surger.268

Three studies fund ear depressin either pre-CABG r immediate pst-CABG t predictcardiac hospitalisation and poorer function/activity at six months.234,236,238 one stud shwed thatsmatic cmpaints were assciated with a simiar predictin.273 This effect was independent f

ther risk factrs. Ear depressin as predicted ikeihd f persisting depressin and wasassciated with ess educatin, ife stressrs, w scia supprt and dspnea.269 one studfound that two screening questions for depression identied those more likely to be readmittedin the fwing si mnths, indicating that a simpe screening methd can identif thse atrisk (see section 6.1).274

Tw studies ked at the impact f gender in CABG and fund that wmen tend t hae prer pschgica heath than men preperatie. The d ess we than men pstperatie atthree and 2 mnths n functin, era heath rating and depressin. 27,272

A study of the inuence of depression on outcomes after angiography found it predicted CABGand PCI rates over the next ve years.275

one case series fund a high psitie iew f sef, future and persna cntr er dai

ife reduced ikeihd f subsequent cardiac eent er fur ears, in patients undergingangipast.276

The eidence indicates that depressin and aniet hae simiar detrimenta effects nutcmes in patients with CABG and angina as in pst-MI patients. The SIGN guideine ncardiac rehabiitatin reprted that cmprehensie cardiac rehabiitatin prgrammes impredmrtait, pschgica and phsica utcmes, and such rehabiitatin prgrammes shudbe cnsidered fr patients with stabe angina after interentins.55

D ptients undergoing coronr rter bss grting shoud receie screening ornxiet nd deression re-surger nd during the ooing er s rt o ostsurgicssessment, rehbiittion nd coronr hert disese secondr reention cinics.where reuired tients shoud receie rorite tretment ( psychological therapy,

rehabilitation, medication).

D Rehbiittion rogrmmes shoud be imemented ter rescuristion or tientsith stbe ngin.

Particuar attentin shud be paid t wmen, thse iing ane and thse under 55ears.

The NICE guideines n management f depressin277 and aniet disrders278 in primar andsecndar care pride recmmendatins fr apprpriate treatments.



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6.5 THE EffECT Of HEalTH BElIEfS ON SyMpTOMS aND fUNCTIONal STaTUS

Indiiduas’ beiefs abut their cnditin are deried frm man surces in additin t medicanes (eg, fami, cutura grup, media).233,282,283 Infrmatin frm cinicians ma be adaptedto t existing beliefs or ignored, thereby inuencing behaviour.279 Cmmn fund beiefs

such as ‘angina is ike a mini-heart attack’ r ‘eer time I get angina I am damaging m heart’,inuence mood and degree of disability.

obseratina studies frm the same research grup hae eamined the causa attributins andbeiefs abut apprpriate cping strategies in patients with stabe angina. The tw quaitatiestudies fund that causa attributins appear simiar t thse with MI.280,28 Mst patients thughtstress was the cause f their angina, wmen were mre ike t attribute angina t stress r uncntrabe causes than their wn preius behaiur and a arge number d nt cite riskfactrs the are knwn t hae. Beiefs were as ike t ead t aidance f actiit andwere maintained b partners.

A similar study compared views of angina patients and peers, nding that peers have greater miscnceptins than patients, which ma reinfrce the netwrk f miscnceptins hed bangina sufferers.282

The yrk Angina Beiefs questinnaire is a 4 item measure f beiefs abut angina. It wasdemnstrated t be a reiabe and aid t t measure miscnceptins and beiefs in anginapatients, which ma ead t aidance f actiit, disabiit and aniet. 283

A stud f 40 patients eamined causa attributins f patients awaiting PCI. Stress, famihistr and chester are cited as causes f CHD prir t PCI b mre femaes than maes.Femaes were mre ike t bame uncntrabe factrs (bigica) than men wh citedbehaiura factrs. There was a discrepanc between patients’ and heathcare prfessinas’iews f causes.284

The Angina Plan is an intervention which identies beliefs about angina, with educationaland management adice taired t ater errneus beiefs and their impact (see section 6.2).An RCT shwed that the Angina Pan successfu changed beiefs and impred functina

utcmes in patients three mnths fwing MI. The interentin grup were mre ptimisticthat iness cud be cntred r cured.233

D ptients’ beies bout ngin shoud be ssessed hen discussing mngement o riskctors nd ho to coe ith smtoms.

B Interentions bsed on schoogic rincies designed to ter beies bout hertdisese nd ngin, such s the angin pn, shoud be considered.





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7 ptient issues nd oo u

During their jurne f care a patient is ike t cme in cntact with a range f heathcareprfessinas whse indiidua res shud be made cear.

A sympathetic approach is needed at all times, with the opportunity for reection and further questining as required. There ma be a need fr erba infrmatin t be reinfrced b writtenr isua infrmatin and there shud awas be an pprtunit t ine fami membersand carers.

7.1 DElIvERING INfORMaTION TO paTIENTS wITH aNGINa – aT DIaGNOSIS aND

pRIOR TO INTERvENTIONS

Patient infrmatin can be prided b means f prepared resurces such as bks, pamphetsand ther printed materia. Use can as be made f audi r ide tapes as we as cmputer software and the internet. Very limited evidence was identied for the effectiveness of anyindiidua frmat er anther.

7.. INFoRMATIoN AND EDUCATIoN ABoUT SURGERy AND oTHER INTERvENTIoNS

Preparing patients fr surger b prisin f infrmatin and addressing cncerns, reducesdistress, ength f sta and the need fr anagesia.285

The educatina interentins described in the eidence were nt standard r deiered at thesame pint in time in reatin t interentins. outcmes as aried between studies.

one RCT priding educatina interentin fr angina patients awaiting angigraph shwedn effect n measures f aniet r we-being after the prcedure.293 one bseratina studshwed the waiting perid prir t eectie catheterisatin is assciated with a negatie impactn patients’ aniet, and reductin in functining and quait f ife.286

Tw RCTs prided differing educatina-tpe interentins prir t CABG, (pain managementbket, and an educatina sessin ear in the ng wait fr CABG). There was n effect npain scores, pain-related interference with activities or on postoperative analgesia in the rststud, nr n aniet, depressin, pain scre, genera we-being and ength f sta. Patientsin bth studies receied ther educatina input as part f standard care. A patients receiedinadequate anagesia, wmen had higher pain scres and nger ength f sta. 287,288

one RCT f a prtc deiered teephne educatina interentin pst CABG did nt shwan effect n aniet f patient r partner at eight weeks.289

Mtiatina interiewing is a structured apprach t heping pepe change behaiur, usingpatient-centred but directed strategies (see SIGN guideline 97 on risk estimation and the

prevention of cardiovascular disease73 and SIGN guideline 57, cardiac rehabilitation55). oneRCT deiering educatin using a mtiatina interiewing apprach b a speciaist cardiacnurse, shared with cmmunit nurses and the supprt f medica practitiners, was shwn tpride effectie reductin in risk factrs, aniet and depressin and impred perceptin f genera heath status during the perid f wait prir t CABG. The heath f patients nt assignedt the treatment interentin deterirated as assessed b utcme measures.290

one RCT prided audi-taped infrmatin n strategies t dea with epected phsicasensatins and their management fwing CABG. This tape was istened t in the ward nthe fourth or fth postoperative day and was taken home by the patient. This showed benet inphsica functining in wmen and pschgica distress, igur and fatigue in men cmparedt usua care.29



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Educatina prgrammes deiered pre- and pst-crnar arter bpass grafting shudcnsider the use f strategies based n pschgica principes t impre managementf risk factrs, pschgica distress and phsica functining.

Patients new diagnsed with angina and thse wh are immediate pre- and

pstinterentins and reascuarisatin, shud be gien apprpriate infrmatin thep them understand their cnditin and hw t manage it, and an prcedure beingundertaken.

Heath beiefs and miscnceptins shud be addressed when deiering infrmatin.

7.2 CaRDIaC waITING TIMES

In 2007 the specied standard waiting time for surgery is 18 weeks from the time of angiography.292 Aderse effects in terms f mrbidit and mrtait ccurring in patients waiting fr inestigatier reascuarisatin prcedures ma be preentabe if waiting times are eiminated.

one RCT f 228 patients which measured a ariet f heath reated quait f ife parametersreeaed that a waiting perid prir t eectie cardiac catheterisatin has a negatie impactn patients’ aniet, with reductin in functining and quait f ife.293

Fr patients waiting fr cardiac interentins, enrment in a nurse-ed educatin prgrammema hep impre shrt term quait f ife.

In an American chrt patients waiting fr crnar angigraph were fwed up fr an aerageof eight months following the procedure and signicant adverse events classied. Comparedwith the eent free grup, patients with aderse eents mre frequent had a histr f knwnCHD (55% s 35%; p=0.03), CCS angina cass III r Iva (42% s 22%; p=0.0), and psitiestress test resuts (69% s 46%; p=0.00).294

lng waiting times fr crnar arter bpass grafting hae been shwn t hae an aderse effect

n phsica and scia functining befre and after surger with an increase in pstperatieaderse effects. In a chrt stud f 360 Dutch patients, the median waiting time fr patientspaced n the eectie surgica waiting ist (86 patients) was 00 das. The primar utcmemeasures f death, mcardia infarctin r unstabe angina requiring hspita admissinccurred in arund 5% f this grup f patients. The majrit f eents ccurred within 30das f being isted fr surger.295

C Er ccess to ngiogrh nd coronr rter bss surger m reduce the risko derse crdic eents nd imired uit o ie.

7.3 fOllOw Up IN paTIENTS wITH aNGINa

Patients presenting with angina t their genera practitiners hae ften been managed withutapprpriate assessment and referra fr pssibe interentin.296

A meta-anasis f cardiac secndar preentin prgrammes with r withut an eerciseprgramme indicated that such prgrammes can hae a psitie effect n the prcess f care,quait f ife as we as reducing the reinfarctin and mrtait rates. 297

Mutidiscipinar disease management prgrammes fr patients with CHD hae been shwn ina systematic review to have a benecial impact on the uptake of secondary prevention drugsand addressing risk factor proles.298 Three trias address fw up in patients with angina.

In the SHIP tria, a cardiac iaisn nurse crdinated care with genera practitiners in patientsdischarged frm hspita with new diagnsed angina.299 Athugh this apprach encuragedfw up it did nt impre bjectie measures f risk ecept in reatin t bd pressure in

the patients with angina p<0.05.

7 paTIENT ISSUES aND fOllOw Up




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Heath prmtin prided b heath isitrs in Befast t patients with angina shwed impredphysical activity and diet with less angina and social isolation after two years. At ve year follow up after recruitment, three years after the end of the intervention, most of the benetshad worn off. Benets in respect of exercise and taking prophylactic drugs, although less, werestill evident (p<0.001 to p<0.05 for both categories).300 This wud suggest that t be effectie

heath prmtin adice needs t be prided n a ng term basis.

In the third tria, patients with a diagnsis f crnar heart disease were recruited t theGrampian nurse-ed secndar preentin cinics ersus rutine care with the aim f prmtingifeste change and secndar preentin. After attending the cinics fr ne ear there was animprement in quait f ife and secndar preentin cmpnents ecept smking. Theseimprements were sustained after fur ears ecept fr eercise. Thse attending the cinicsas had fewer tta deaths and crnar eents.30 After adjusting fr age, se and baseinesecndar preentin, the prprtina hazard ratis were 0.75 fr a deaths (95% CI 0.58 t0.98; p=0.036) and 0.76 fr crnar eents (95% CI 0.58 t .00; p=0.049).

Tw further studies cnsisting f nurse r GP fw up with audit feedback302 and pstaprmpts303 did not lead to signicant benets in secondary prevention. Provision of the

Angina Pan t patients with angina did ead t an imprement in reprted diet and daiwalking (p<0.001).4

a ptients resenting ith ngin nd ith dignosis o coronr hert disese shoudreceie ong term structured oo u in rimr cre.



8 Sources o urther inormtion nd suort or

tients nd crers British Crdic ptients associtionBCPA Head Ofce2 Statin RadSwaese, Cambridge, CB4 5QJTe: 0800 479 2800 Fa: 0954 202 022Emai: [email protected] www.bcpa.c.uk

The British Cardiac Patients Assciatin is a charitabe rganisatin run b unteers pridingsupprt, adice and infrmatin t cardiac patients and their carers.

British Hert foundtion (Scotnd)4 Shre Pace

EdinburghEH6 6WWTe: 03 555 589 Heart Infrmatin ine: 08450 70 80 70 (aaiabe Mn-Fri 9am-5pm)Emai: [email protected] www.bhf.rg.uk

British Heart Fundatin prides a teephne infrmatin serice fr thse seeking infrmatinn heart heath issues. As prides a range f written materias ffering adice and infrmatint CHD patients and carers. Tpics incude phsica actiit, smking and diabetes.

Chest Hert nd Stroke Scotnd 65 Nrth Caste StreetEdinburghEH2 3lTTe: 03 225 6963 Hepine: 0845 0776000Emai: [email protected] www.chss.rg.uk

Chest Heart and Stroke Scotland provides a 24 hour advice line offering condential, independentadice n a aspects f chest, heart and strke iness. A series f infrmatin bkets, factsheetsand ides is aaiabe free f charge t patients and carers. There are er 30 cardiac supprtgroups in Scotland which are afliated to CHSS, patients can contact CHSS for details of their nearest ca supprt grup.

Deression aince Scotnd3 Grsenr GardensEdinburghEH2 5JUTe: 03 467 3050Emai: [email protected] www.depressinaiance.rg

Depressin Aiance Sctand prides infrmatin and supprt fr pepe in Sctand whhae depressin.

Hert Surger in Gret Britin http://heartsurgery.healthcarecommission.org.uk/

This website has been deeped b the Heathcare Cmmissin and the Sciet fr Cardithracic Surger in Great Britain and Ireand t hep heart surger patients make infrmed

chices abut their treatment. It prides patients and carers with infrmatin n the differentoperations available and the benets of having heart surgery.

8 SOURCES Of fURTHER INfORMaTION fOR paTIENTS aND CaRERS




NHS Heth ScotndWoodburn HouseCanaan laneEdinburgh, EH0 4SGTe: 03 536 5500 Textphone: 03 536 5503

Fax: 03 536 550 Emai: [email protected] (information on obtainingHeath Scotand pubications); [email protected] (hep with genera heathinformation enquiries) www.hebs.com

NHS Heath Scotand is a specia heath board within NHS Scotand. The organisation providesinformation on projects, publications, support groups and information leaets relating toCHD.

Hert Mnu DeprtmentAdministration Buiding,Astey Ainsie Hospita,Grange loan, Edinburgh EH9 2Hl

Tel: 0131 537 9127 / 9137 Emai: [email protected] • www.theheartmanua.com

The Heart Manua is the UK’s eading home based rehabiitation programme for patientsrecovering from acute myocardia infarction. The programme is deivered by heathprofessionas who have competed a two day faciitator training course. It provides astandardised approach for more than 250 major NHS users across the UK and Ireand, and isin use in a number of overseas countries. It contributes to the recovery of more than 2,000heart attack patients per year and has been shown to be cinicay effective in studies.

NHS 24www.nhs24.com

Te: 0845 4 24 24 24

NHS 24 is a nurse-ed service for members of the pubic. It is a hepine offering heathinformation, advice and hep over the phone.

Scotnd’s Heth on the web www.show.scot.nhs.uk

This website provides pubic access to pubications reating to CHD such as the strategy for CHD and stroke in Scotand.




Psychological and cognitive issues

What are the mechanisms by which depression inuences mortality following CABG?

Mre rbust studies are required n the reatinship between patient reprting f cgnitieimpairment and measurabe impairment.

Further clarication is needed on the role of non-surgical factors in determining whichpatients wi demnstrate cntinued cgnitie impairment fwing CABG.

An interentin stud is needed n the effect f screening fr high ees f depressinand aniet pre-CABG and deier f ear pstperatie rehabiitatin and pschgicainterentin, n patient utcmes and use f heath serice resurces.

An ecnmic anasis f heath serice use is required in patients with angina with highees f miscnceptins and emtina distress.

Patient issues and follow up

What is the ptimum reiew intera in primar care fr patients with estabished

cardiascuar disease?

9.4 aDDITIONal aDvICE TO NHSSCOTlaND fROM NHS qIS aND THE SCOTTISHMEDICINES CONSORTIUM

9.4. NHS QIS APPRovED NICE MTAS

The fwing reprts hae been appred b NHS Quait Imprement Sctand.

NICE Techng Appraisa Guidance N 5 – The use f cmputerised cgnitie behaiur therap fr aniet and depressin.304

NICE Techng Appraisa Guidance N 52 – The use f drugs fr ear thrmbsis in thetreatment f acute mcardia infarctin.305

NICE Techng Appraisa Guidance N 7 – Ischaemic heart disease - crnar arter stents

(reiew).306

NICE Techng Appraisa Guidance N 80 – Acute crnar sndrmes – cpidgre. 307

NICE Technology Appraisal Guidance 90 – Clopidogrel and modied-release dipyridamole inthe preentin f ccusie ascuar eents.308

NICE Techng Appraisa Guidance N 94 – Statins fr the preentin f cardiascuar

eents.309

9.4.2 SMC ADvICE

The Scttish Medicines Cnsrtium has issued adice n the use f iabradine (octber 2006).30 Adice n a number f indiidua prducts within the fwing drug casses; statins, angitensinreceptr bckers, beta bckers and direct thrmbin inhibitrs is as aaiabe.

Further detais are aaiabe frm www.scttishmedicines.rg.uk



10 Deeoment o the guideine

10.1 INTRODUCTION

SIGN is a cabratie netwrk f cinicians, ther heathcare prfessinas and patientrganisatins and is part f NHS Quait Imprement Sctand. SIGN guideines are deepedb mutidiscipinar grups f practising cinicians using a standard methdg based n asstematic reiew f the eidence. Further detais abut SIGN and the guideine deepmentmethdg are cntained in “SIGN 50: A Guideine Deeper’s Handbk”, aaiabe at.sign.c.uk

10.2 THE GUIDElINE DEvElOpMENT GROUp

Dr Aan Begg (Chair) General Practitioner, Montrose

Ms Shna Back Cardiovascular Facilitator, Dundee Community Health

PartnershipMr Tm Brightn Lay Representative, Montrose

Dr Rb Cargi Consultant Cardiologist, Victoria Hospital, Kirkcaldy

Ms Jce Craig Senior Health Economist,

NHS Quality Improvement Scotland

Dr Mhamed Efeah Cardiovascular Lead Pharmacist, Aberdeen Royal Inrmary

Dr Nei Giespie Senior Lecturer, Section of Ageing and Health,

University of Dundee

Mr Bb Jeffre Consultant Cardiothoracic Surgeon,

Aberdeen Royal Inrmary

Dr Alistair Mace Consultant Anaesthetist, Western Inrmary, Glasgow Mrs Catrina McGregr Head of Clinical Physiology, Ayr Hospital

Mr Aeander Massn Lay Representative, Montrose

Dr Jhn Mine General Practitioner, Leslie Medical Practice, Glenrothes

Dr Mra Nairn Programme Manager, SIGN Executive

Dr Keith odrd Interventional Cardiologist, Western Inrmary, Glasgow

Mr Dennis Sandeman Chest Pain Nurse Specialist, Victoria Hospital, Kirkcaldy

Mr Duncan Serice Information Ofcer, SIGN Executive

Ms Nica Stucke Consultant Clinical Psychologist,

Astley Ainslie Hospital, Edinburgh

The membership of the guideline development group was conrmed following consultationwith the member rganisatins f SIGN. A members f the guideine deepment grupmade decaratins f interest and further detais f these are aaiabe n request frm the SIGNEecutie. Guideine deepment and iterature reiew epertise, supprt and faciitatin wereprided b the SIGN Eecutie.

10 DEvElOpMENT Of THE GUIDElINE




10.3 THE STEERING GROUp

A steering group comprising the chairs of the ve SIGN CHD guidelines and other invitedeperts was estabished t ersee the prgress f guideine deepment. This grup metreguar thrughut the deepment f the guideines.

Dr Kein Jennings Co-chair and Consultant Cardiologist,


Prfessr lewis Ritchie Co-chair and Mackenzie Professor of General Practice,University of Aberdeen

Dr Aan Begg Chair of SIGN stable angina guideline

Dr Nick Bn Consultant Cardiologist, Royal Inrmary of Edinburgh

Ms Marjr Burns Director for Scotland, British Heart Foundation

Mr Daid Cark Chief Executive, Chest, Heart and Stroke Scotland

Prfessr Stuart Cbbe Chair of SIGN arrhythmias guideline

Ms Jce Craig Senior Health Economist, NHS Quality Improvement Scotland

Dr Iain Finda Chair of SIGN acute coronary syndromes guideline

Prfessr Keith F Professor of Cardiology, University of Edinburgh

Dr James Grant Chair of SIGN prevention guideline

Mr James Grant Lay representative, Balerno

Dr Grace lindsa Reader in Clinical Nursing Research,

Glasgow Caledonian University

Dr Mra Nairn Programme Manager, SIGN

Prfessr Aan Struthers Chair of SIGN heart failure guideline

Dr lrna Thmpsn Programme Manager, SIGN

10.4 SySTEMaTIC lITERaTURE REvIEw

The eidence base fr this guideine was snthesised in accrdance with SIGN methdg. Asstematic reiew f the iterature was carried ut using an epicit search strateg deised ba SIGN Information Ofcer. Searches were focused on existing guidelines, systematic reviews,randomised controlled trials, and (where appropriate) observational and/or diagnostic studies.Databases searched incude Medine, Embase, Cinah, PschINFo, and the Cchrane librar.The ear range cered was 999-2005. Internet searches were carried ut n arius websitesincuding thse fr the Austraian Centre fr Cinica Effectieness, Natina Institute fr Heathand Cinica Eceence, the Natina librar fr Heath, Swedish Cunci n TechngAssessment in Heathcare, US Agenc fr Heathcare Research and Quait, and the US NatinaGuideines Cearinghuse. The Medine ersin f the main search strategies can be fund n

the SIGN website, in the sectin cering suppementar guideine materia. The main searcheswere supplemented by material identied by individual members of the development group.Each f the seected papers was eauated b tw members f the grup using standard SIGNmethdgica checkists befre cncusins were cnsidered as eidence.

10.5 CONSUlTaTION aND pEER REvIEw

0.5. NATIoNAl oPEN MEETING

A natina pen meeting is the main cnsutatie phase f SIGN guideine deepment, atwhich the guideline development group presents its draft recommendations for the rst time.The national open meeting for the ve parallel SIGN guidelines on aspects of cardiovascular disease was hed n 6 September 2005 and was attended b er 600 representaties f

a the ke speciaties reeant t the guideine. The draft guideine was as aaiabe n theSIGN website fr a imited perid at this stage t aw thse unabe t attend the meeting tcntribute t the deepment f the guideine.



0.5.2 SPECIAlIST REvIEW

This guideine was as reiewed in draft frm b the fwing independent epert referees,wh were asked t cmment primari n the cmprehensieness and accurac f interpretatinf the eidence base supprting the recmmendatins in the guideine. SIGN is er gratefut a f these eperts fr their cntributin t the guideine.

Prfessr Adrian Bagust Professor of Cardiology, University of Liverpool

Mr Ae Cae Cardiac Surgeon, Castle Hill Hospital, North Humbershire

Prfessr Stuart Cbbe Consultant Cardiologist, Glasgow Royal Inrmary

Ms Irene Crawfrd Senior Chief Cardiac Physiologist,

Golden Jubilee Hospital, Glasgow

Dr Macm Danie Consultant Anaesthetist, Glasgow Royal Inrmary

Mrs Frances Diers Cardiac Nurse Specialist, St John’s Hospital, Livingston

Dr Frank Dunn Consultant Cardiologist, Stobhill Hospital, Glasgow

Ms Karen Fetcher CHD and Stroke Prevention Coordinator,

Angus CHP, Forfar

Prfessr Kim F Professor of Cardiology, Royal Brompton Hospital, London

Dr Jhn Giies General Practitioner, The Health Centre, Selkirk

Dr Grant Hadane Consultant Anaesthetist, Hairmyres Hospital, East Kilbride

Mr Martin Haes Senior Chief Cardiac Physiologist,

Western General Hospital, Edinburgh

Dr Graham Hiditch Consultant Anaesthetist,

Gartnavel General Hospital, Glasgow

Dr Graham Hiis Senior Lecturer and Honorary Consultant Cardiologist,

Aberdeen Royal Hospitals NHS Trust

Dr Harpreet Khi Head of Health Services Research and Development,

NHS Quality Improvement Scotland, Glasgow

Dr Sand Kpt Principal Clinical Pharmacist, Victoria Hospital, Kirkcaldy

Prfessr Chim lang Professor of Cardiology,

Ninewells Hospital and Medical School, Dundee

Ms lnne MacBeth Senior Chief Cardiac Physiologist, Aberdeen Royal Inrmary

Dr Macm Metcafe Consultant Cardiologist, Aberdeeen Royal Inrmary

Dr Stewart Mine Consultant Anaesthetist, Glasgow Royal Inrmary

Prfessr Daid Newb British Heart Foundation Reader and Consultant Cardiologist,

University of Edinburgh

Dr Aistair Nimm Consultant Anaesthetist, Royal Inrmary of Edinburgh

Mr Daid Pau Lay Reviewer, Glasgow

Prfessr Stuart Pringe Consultant Cardiologist,


Ms Fina Reid Pharmacist, NHS Lothian

Dr Karen Smith Clinical Research Fellow (Cardiac Nursing),


Prfessr Daid Taggart Cardiac Surgeon, John Radcliffe Hospital, Oxford

Mrs Audre Thmpsn Senior Medicines Management Adviser,

Gartnavel Royal Hospital, Glasgow

Dr Stephen Watn Consultant Cardiologist, Aberdeen Royal Inrmary

Dr Ae Watsn General Practitioner, West Gate Health Centre, Dundee

10 DEvElOpMENT Of THE GUIDElINE




0.5.3 SIGN EDIToRIAl GRoUP

As a nal quality control check, the guideline is reviewed by an editorial group comprisingmembers f SIGN Cunci t ensure that the speciaist reiewers’ cmments hae been addressedadequate and that an risk f bias in the guideine deepment prcess as a whe has beenminimised. The editria grup fr this guideine was as fws:

Dr Daid Aeander Member of SIGN Council

Dr Keith Brwn Member of SIGN Council

Prfessr Hiar Cape Member of SIGN Council

Mr Rbert Carachi Member of SIGN Council

Dr Kein Jennings Co-chair SIGN CHD Steering Group and Consultant Cardiologist,


Dr Jhn Kinsea Member of SIGN Council

Prfessr Grdn lwe Chair of SIGN; Co-Editor

Ms Anne Matthew Member of SIGN Council

Mr Chris oier Member of SIGN Council

Dr Saa Qureshi SIGN Programme Director; Co-Editor

Prfessr lewis Ritchie Co-chair SIGN CHD Steering Group and Mackenzie Professor

of General Practice, University of Aberdeen

Dr Sara Twadde Director of SIGN; Co-Editor

10.6 aCKNOwlEDGEMENTS

SIGN is gratefu t the fwing frmer members f the guideine deepment grup andthers wh hae cntributed t the deepment f this guideine.

Ms Jenni Brckie Information Ofcer, SIGN Executive

Mr Iain lwis Head of Community Fundraising,

British Heart Foundation, Edinburgh

Dr oiia Wu Systematic Reviewer, Glasgow University



MaNaGEMENT Of STaBlE aNGINaMaNaGEMENT Of STaBlE aNGINa

lMS eft main stem

lv eft entricuar

lvEf eft entricuar ejectin fractin

lvSD eft entricuar sstic dsfunctin

MaSTER Muticentre Austraian Stud f Epidura Anaesthesia tria

MET metabic equiaent f task

MI mcardia infarctin

MpS mcardia perfusin scintigraph

MRI magnetic resnance imaging

MTa mutipe techng assessment

NICE Natina Institute fr Heath and Cinica Eceence

NNT number needed t treat

NyHa New yrk Heart Assciatin

OR dds rati

pEaCE Preentin f Eents with Angitensin Cnerting Enzme inhibitin tria

pCI percutaneus crnar interentin

pTCa percutaneus transumina crnar angipast

qOf quait utcmes framewrk

qol quait f ife

qUIET QUinapri Ischemic Eent Tria

RaCpC rapid access chest pain cinic RCa right crnar arteries

RCRI reised cardiac risk inde

RCT randmised cntred tria

RD risk difference

RR reatie risk

SHIp Suthamptn Heart Integrated care Prject tria

SIGN Scttish Intercegiate Guideines Netwrk

SMC Scttish Medicines Cnsrtium

SvD singe esse crnar arter disease

SvG saphenus ein grafts

SvT supraentricuar tachcardia

TaR tta arteria reascuarisatin

TENS transcutaneus eectrica nere stimuatr

TMR transmcardia reascuarisatin

TvD tripe esse crnar arter disease

UKCSR UK Cardiac Surgica Register

vO2 mx maimum gen cnsumptin

vTE enus thrmbembism




28 Natina Institute fr Heath and Cinica Eceence.Mcardia perfusin scintigraph fr the diagnsisand management f angina and mcardia infarctin.lndn: NICE; 2003. (NICE Techng Appraisa73). [cited 6 Oct 2006] Available from url: http:// www.nice.org.uk/page.aspx?o=TA073guidance

29 Mwatt G, vae l, Brazei M, Hernandez R, MurraA, Sctt N et a. Sstematic reiew f the effectienessand cst-effectieness and ecnmic eauatin f mcardia perfusin scintigraph fr the diagnsis f angina and mcardia infarctin. Heath TechngAssessment 2004; 8(30):-207.

30 NHS Natina Serices Sctand. Infrmatin andStatistics Diisin. (Persna cmmunicatin)

3 Jeete P, Burden l, Senir R. Stress echcardigraphis superior to exercise ECG in the risk straticationf patients presenting with acute chest painwith negatie trpnin. Eur J Echcardigr.2006;7(2):55-64.

32 Senir R, Mnaghan M, Becher H, Maet J,Nihannpus P. Stress echcardigraph fr the diagnosis and risk stratication of patients with

suspected r knwn crnar arter disease: acritica appraisa. Heart 2005;9(4):427-36.

33 Budff MJ, Achenback S, Duerinck A. Cinica utiitf cmputed tmgraph and magnetic resnancetechniques fr nn-inasie crnar angigraph.

J Am C Cardi 2003;42():867-8.34 Department f Heath. Crnar heart disease:

natina serice framewrk fr crnar heartdisease. lndn: The Department; 2000.[cited 6 Oct 2006]. Available from url: http:// www.dh.gov.uk/PublicationsAndStatistics/ Publications/PublicationsPolicyAndGuidance/ PublicationsPolicyAndGuidanceArticle/fs/ en?CoNTENT_ID=4094275&chk=eTacC

35 Dugan JP, Mathew TP, Ridde JW, Spence MS,

McGinche PG, Nesbitt GS, et a. Suspected anginapectris: a rapid-access chest pain cinic. QJM200;94(2):679-86.

36 Heidenreich PA, McDnad KM, Hastie T,Fade B, Hagan v, lee BK, et a. Meta-anasisf trias cmparing beta bckers, caciumantagnists, and nitrates fr stabe angina. JAMA.999;28(20):927-36.

37 Heidenreich PA, McDnad KM, Hastie T, FadeB, Hagan v, lee BK, et a. An eauatin f beta bckers, cacium antagnists, nitrates, andaternatie therapies fr stabe angina. Rckie(MD): AHRQ; 1999. (Evidence Report/TechnologyAssessment N.0). [cited 6 oct 2006] Aaiabefrom url: http://www.ncbi.nlm.nih.gov/books/ b.fcgi?rid=hstat.chapter.4350

38 Scupher MJ, Petticrew M, Keand Jl, Eitt RA,Hdright DR and Butn MJ. Resurce acatinfr chrnic stabe angina: a sstematic reiew f the effectieness,csts and cst-effectieness f aternatie interentins. Heath Techn Assess.998;2(0):i-i, -76.

39 Nidrf SM, Parsns, RW, Thmpsn Pl, JamrzikKD, Hbbs MS. Reduced risk f death at 28 dasin patients taking a beta bcker befre admissint hspita with mcardia infarctin. BMJ 990;300(677):7-4.

40 yusuf S, Pet R, lewis J, Cins R, Seight P. Betabckade during and after mcardia infarctin: aneriew f the randmised trias. Prg CardiascDis 985;27(5):335-7.

4 Bunch TJ, Muhestein JB, Bair Tl, Renund DG, lappeDl, Jensen KR et a. Effect f beta bcker therapn mrtait rates and future mcardia infarctinrates in patients with crnar arter disease but nhistr f mcardia infarctin r cnjestie heartfaiure. Amer J Cardi 2005;95(7):827-3.

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44 Midtb K, Mstad P; AMSA stud grup (AmdipineMetpr Stabe Angina). Amdipine ersussw reease metpr in the treatment f stabe eertina angina pectris (AMSA). ScandCardiasc J. 2000;34(5):475-9.

45 Chugh SK, Digpa K, Hutchinsn T, McDnad CJ,Mier AJ, lahiri A. A randmized, dube-bindcomparison of the efcacy and tolerability of once-

daily modied-release diltiazem capsules with once-dai amdipine tabets in patients with stabe angina.

J Cardiasc Pharmac. 200;38(3):356-64.46 Chn JN, Ziesche S, Smith R, Anand I, Dunkman WB,

leb H et a. Effect f cacium antagnist fedipineas suppementar asdiatr therap in patients withchrnic heart faiure treated with enaapri. v-HeFTIII. vasdiatr-Heart Faiure Tria (v-HeFT) StudGrup. Circuatin 997;96(3):856-63.

47 Packer M, o’Cnnr CM, Ghai JK, Presser Ml,Carsn PE, Bekin RN, et a. Effect f amdipinen mrbidit and mrtait in seere chrnic heartfaiure. Prspectie Randmized AmdipineSuria Eauatin Stud Grup. N Eng J Med.996;335(5):07-4.

48 Scttish Intercegiate Guideines Netwrk.Management f chrnic heart faiure. Edinburgh;SIGN: 2007. (SIGN Guideine n. 95).

49 Stasn WB, Schmid CH, Niedzwiecki D, WhitingGW, Caubet JF, Cr D, et a. Safet f nifedipinein angina pectris: a meta-anasis. Hpertensin.999;33():24-3.

50 Timant Py, labanche JM, Thieueu FA, DupuisBA, Bertrand ME. Detrimenta effect f prpranin patients with crnar arteria spasm cunteredb a cmbinatin with ditiazem. Am J Cardi983;52(3):230-3.

5 Chahine RA, Fedman Rl, Gies TD, Nicd P,Raizner AE, Weiss RJ, et a. Randmized pacebcntred tria f amdipine in asspastic angina.Amdipine stud 60 grup. J Am C Cardi

993;26:365-70.52 Guermnprez Jl, Bin P, Peterng F. A dube-

bind cmparisn f ng-term efficac f aptassium channe pener and a cacium antagnistin stabe angina pectris. Eur Heart J 993;4 (SuppB): B30-34.

53 Chatterjee T. Feisch M. Meier B. Eber A.Cmparisn f the antiischaemic and antianginaeffect f nicrandi and amdipine in patients withsmptmatic stabe angina pectris: the SWANstud. J Cin Basic Cardi 999;2(2):23-7.

54 IoNA Stud Grup. Effect f nicrandi n crnareents in patients with stabe angina: the impact f nicrandi in angina (IoNA) randmised tria. lancet2002;359(934):269–75.

55 Waker A, McMurra J, Stewart S, Berger W,McMahn AD, Dargie H, et a. Ecnmic eauatinf the impact f nicrandi in angina (IoNA) tria.Heart. 2006;92(5):69-24.



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Angina Mngmt

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