NAO, Fibrillazione Atriale e Sindromi Coronariche Acute ... · PDF fileSTEMI Elective BMS...
Transcript of NAO, Fibrillazione Atriale e Sindromi Coronariche Acute ... · PDF fileSTEMI Elective BMS...
Marco Botta
S.C. Cardiologia
Ospedale San Paolo di Savona
NAO, Fibrillazione Atriale e Sindromi
Coronariche Acute: luci ed ombre
… un po’ di luce …. ancora molte ombre …
ACSPCI (DES – BMS)
Coronary Ischemia
AFDVTPELV thrombus(Mechanical) valves
Stroke
Condition
Aim :
BACKGROUND
Coronary IschemiaStent thrombosis
DAPT better than OAC
1 – 6 – 12 months
StrokeSystemic embolism
OAC better than DAPT
Sometimes lifelong
Aim :Prevention
Evidence
Duration
Condition Drugs Duration
1 year
1 year
1 month
RecommandationEvidence Level
I A
I A (B)
I A (B)
DAPTNSTEMI
STEMI
Elective BMS
Recent GUIDELINES
1 month6 months
I A (B)I A (B)
VKANOACS
LifelongI A
Elective BMSElective DES
AF
LOV 2014
• Nearly 10-30% of patients with acute coronary syndrome (ACS) have AF.
• Anticoagulated patients with AF presenting with an ACS or with chronic ischaemic
Editorial FocusAntithrombotic therapy in atrial fibrillation and st ent implantation: treatment or
threats by the use of triple or dual antithrombotic therapy.
Francisco Marín, Kurt Huber, Gregory Y. H.
• Anticoagulated patients with AF presenting with an ACS or with chronic ischaemicheart disease undergoing percutaneous coronary intervention (PCI) with stent implantation represent a complex management cohort, especially from the concomitant use of dual antiplatelet therapy required after stent implantation, leading to triple therapy (TT).
• In these patients, one has to balance the risk of stroke (from AF), recurrent cardiac ischemia (if ACS), stent thrombosis and serious bleeding.
Thrombosis and Haemostasis 110.4/2013
CHA2DS2-VASc Score
HAS-BLED Risk Score
ESC Guidelines. European Heart Journal 2010; 31
HAS-BLED >= 3: indicates "high risk" and some caution and regular review of the patient is needed
The Pharmacology Confusion…
�Both ischemic complications and bleeding complications have significant impact on clinical outcome.
�The most effective antithrombotic treatment will
Thrombosis VS Bleeding
be associated with increase in bleeding complications.
�The safest antithrombotic treatment in terms of bleeding will be associated with increase in ischemic complications.
How to square the circle ?
ANTITHROMBOTIC THERAPY
Antipiastrinici
Orali:-Asa-Ticlopidina-Clopidogrel-Prasugrel-Ticagrelor
Eparine
-Eparine bpm-Fondaparinux-Eparina sodica
Anticoagulanti Orali
-Warfarin-Acenocumarolo
-Dabigatran-Rivaroxaban-Apixaban
Bivalirudina-Ticagrelor
Endovenosi:-Asa-Inibitori IIb-IIIaAbciximabEptifibatideTirofibam
-Apixaban
Fibrinolitici
-rtPA-Tenecteplase
Double and Triple Therapy Antipiastrinici Orali + Anticoagulanti Orali
Quale OAC e Quale Terapia
Antipiastrinica…
… Dati su Double o Triple Therapy… Dati su Double o Triple Therapy
con Warfarin
The WOEST Trial: First randomised trial comparing two regimens with and without aspirin in patients on oral anticoagulant therapy undergoing coronary stenting
Willem Dewilde, Tom Oirbans, Freek Verheugt, Johannes Kelder, Bart De Smet, Jean-Paul Herrman, Tom Adriaenssens, Mathias Vrolix,
WOEST ESC, Hotline III, Munchen, August 28th, 2012
|
De Smet, Jean-Paul Herrman, Tom Adriaenssens, Mathias Vrolix, Antonius Heestermans, Marije Vis, Saman Rasoul, Kaioum
Sheikjoesoef, Tom Vandendriessche, Carlos Van Mieghem, Kristoff
Cornelis, Jeroen Vos, Guus Brueren, Nicolien Breet and Jurriën ten Berg
The WOEST Trial= What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing
(clinicaltrials.gov NCT00769938)
Study Design-2
1:1 Randomisation:
Double therapy group:
OAC + 75mg Clopidogrel qd
1 month minimum after BMS
Triple therapy group
OAC + 75mg Clopidogrel qd + 80mg Aspirin qd
1 month minimum after BMS
WOEST
|
1 month minimum after BMS
1 year after DES
1 month minimum after BMS
1 year after DES
Follow up: 1 year
Primary Endpoint: The occurence of all bleeding events (TIMI criteria )
Secondary Endpoints:- Combination of stroke, death, myocardial infarction , stent thrombosis andtarget vessel revascularisation
- All individual components of primary and secondary endpoints
Primary Endpoint: Total number of TIMI bleeding eve nts
Cum
ulat
ive
inci
denc
e of
ble
edin
g
30 %
40 %
50 % Triple therapy groupDouble therapy group 44.9%
19.5%
WOEST
|
Days
Cum
ulat
ive
inci
denc
e of
ble
edin
g
0 30 60 90 120 180 270 365
0 %
10 %
20 %
284 210 194 186 181 173 159 140n at risk: 279 253 244 241 241 236 226 208
19.5%
p<0.001
HR=0.36 95%CI[0.26-0.50]
Secondary Endpoint (Death, MI,TVR, Stroke, ST)
Cum
ulat
ive
inci
denc
e
10 %
15 %
20 %17.7%
11.3%
Triple therapy groupDouble therapy group
WOEST
Days
Cum
ulat
ive
inci
denc
e
0 30 60 90 120 180 270 365
0 %
5 %
284 272 270 266 261 252 242 223n at risk: 279 276 273 270 266 263 258 234
p=0.025
HR=0.60 95%CI[0.38-0.94]
All-Cause Mortality
Cum
ulat
ive
inci
denc
e of
dea
th
5 %
7.5 %
6.4%
HR=0.39 95%CI[0.16-0.93]
p=0.027
Triple therapy groupDouble therapy group
WOEST
Days
Cum
ulat
ive
inci
denc
e of
dea
th
0 30 60 90 120 180 270 365
0 %
2.5 %
284 281 280 280 279 277 270 252n at risk: 279 278 276 276 276 275 274 256
2.6%
Trial’s Conclusions1. First randomized trial to address the optimal antiplatelet therapy in patients on OAC
undergoing coronary stenting
2. In this study which was specifically designed to detect bleeding events, the bleeding
rate was higher than expected
WOEST
|
3. Primary endpoint was met: OAC plus clopidogrel causes less bleeding than triple
antithrombotic therapy, but now shown in a randomized way
4. Secondary endpoint was met: with double therapy there is no excess of
thrombotic/thromboembolic events: stroke, stent thrombosis, target vessel
revascularisation, myocardial infarction or death
5. Less all-cause mortality with double therapy
ISAR Triple - Am Heart J - TCT 2014
614 pz. Dopo impianto di DES in ASA + Warfarin + 6 wee k or 6 month of Clopidogrel (307 and 307)
Benefit and Safety With Triple Therapy Versus Dual Therapies
Triple therapy (oral anticoagulant [OAC] plus aspirin plus clopidogrel [dotted line]) isused as reference (hazard ratio ¼1.00).
Orange circles indicate OAC plus clopidogrel
Yellow circles indicate OAC plus aspirin
Green circles indicate aspirin plus clopidogrel. MI ¼ myocardial infarction.
In real-life AF patients with indication for multipleantithrombotic drugs after MI/PCI, OAC andClopidogrel was equal or better on both benefit andsafety outcomes compared to triple therapy.
Warfarin and New P2Y 12: Pochi Dati…
In both
PLATO (Ticagrelor)and
TRITON-TIMI 38 (Prasugrel)Studies
Patients were excluded from enrollment
if receiving VKA
Warfarin and New P2Y 12: Pochi Dati…
Warfarin and New P2Y 12: Ongoing Trial…
CONCLUSIONS
The efficacy of triple therapy (VKA, aspirin, and clopidogrel) in AF
patients who need to undergo PCI with stent placement has
never been proven, but this strategy increases bleeding risk never been proven, but this strategy increases bleeding risk
significantly. New evidence, including a randomized controlled
trial and a real-life nationwide registry of more than 12,000
patients, showed the great potential of the combination of VKA
and clopidogrel without aspirin to improve clinical outcomes in
comparison with triple therapy.
Therefore, VKA combined with clopidogrel seems to be a
reasonable alternative to triple therapy in patients on long-
term VKA who undergo PCI and stenting.
Quale OAC e Quale Terapia
Antipiastrinica …
… Dati su Double o Triple Therapy… Dati su Double o Triple Therapy
con New Oral Anticoagulants
ASA CLOPIDOGRELASA+
CLOPIDOGREL
40% 6% 4%
Trattamento Antiaggregante nei Trials sui NAO
37% n.d.
31% 2%
SUBGROUP RELY
SUBGROUP RELY
SUBGROUP ROCKET-AF
SUBGROUP ARISTOTLE
RE-DEEM Trial Conclusions
• The study was not powered to demonstrate an efficac y difference in cardiovascular death, nonfatal myocardial infarc tion or non haemorragic stroke
• A dose-dependent increase in clinically relevant bl eeding events was observed, with highest rates whit the dose of 1 10 and 150 mg of Dabigatran
ATLAS ACS 2 TIMI 51 Conclusions: Compared with placebo, Rivaroxaban
(2.5 or 5 mg bid) on top of ASA or ASA plus clopidogrel showed:
– Significant reductions in the rates of death, MI , and stroke
– Benefits in all types of ACS patients (UA, NSTEMI and STEMI )
– More than a 30% reduction in risk of both CV and all-cause mortality
(2.5 mg bid)
N Engl J Med 2011
(2.5 mg bid)
– No increase in fatal bleeding and fatal ICH
– A non-bleeding safety profile similar to placebo
The addition of anticoagulation with rivaroxaban may represent a new
treatment strategy in patients after recent ACS
ApixabanApixaban with antiplatelet therapy with antiplatelet therapy
after acute coronary syndromeafter acute coronary syndrome
The APPRAISEThe APPRAISE--2 trial2 trial
NEJM 2011; 365:699
Cardiac death, MI or stroke occurred in 7.5% of patients on apixaban and 7.9% of patients on placebo
Major bleeding occurred in 1.3% of patients on apixaban and 0.5% of patients on placebo
Conclusions: Apixaban increased major bleeding event s but did not significantly reduce recurrent ischemic events
No Data on New P2Y12
PRASUGRELTICAGRELOR
In patient with a recent acute coronary syndrome, the additi on of anew oral anticoagulant to antiplatelet therapy results in a modestreduction in cardiovascular events but a substantial incre ase inbleeding, most pronounced when new oral anticoagulants arecombined with dual antiplatelet therapy.
PIONEER AF-PCI: study design
Open label, randomized, controlled, multi-center study exploring
two treatment strategies of RivaroxabanRivaroxaban and a dose adjusted oral
VKA treatment strategy in patients with AF who undergo PCI
Rivaroxaban 15 mg OD*#+ clopidogrelN= 2100
Ongoing Trial
3232Clinicaltrials.gov: NCT01830543
Study population: patients with paroxysmal, persistent or
permanent AF
End of
treatment
(12 months)
*: reduced to 10 mg OD in patients with CrCl 30-50 ml/min#: first dose administered 72-96 h after sheath removal§: first dose administered 12-72 h after sheath removal
1:1:1
R
Rivaroxaban 2.5 mg BID§
+DAPTPCI (with
stent placeme
nt)
VKA (target INR 2-3)§
+DAPT
Rivaroxaban 15 mg OD*
+ low dose ASA
VKA + low dose ASA
Intended DAPT duration
Of 1,6 or 12 months
The RE-DUAL PCI™ trial (Randomized Evaluation of Dual Therapy with DabigatranDabigatran vs. Triple Therapy Strategy with Warfarin in Patients with NVAF that have undergone PCI with Stenting)
Patients undergoing PCI
Dabigatran (150 mg or 110 mg twice daily) + single antiplatelettherapy with a P2Y12 protein inhibitor therapy with a P2Y12 protein inhibitor compared to warfarin + two antiplatelet agents
to assess clinically relevant bleeding and thrombotic events (combined rate of death, myocardial infarction and stroke)
Le attuali RACCOMANDAZIONI ….
Eur Heart J Sept 2014
Eur Heart J Sept 2014Se N OAC: Dabigatran 110 mg, Rivaroxaban 15 mg, Apixaban 2,5 mg
Recommended antithrombotic strategies following coronary stenting in patients
with atrial fibrillation at moderate-to-high thromboembolic risk
(in whom OAC therapy is required)
OAC and Clopidogrel may be an alternative
2014 ESC/EACTS
GUIDELINES ON
MYOCARDIAL
REVASCULARIZATION
OAC and Clopidogrel may be an alternative
OAC and Clopidogrel may be an alternative
ESC-EHRA-EAPCI-ACCA-HRS-
APHRS
Eur Heart J Aug 2014
JOINT CONSENSUS DOCUMENT
Antithrombotic Management in Atrial Fibrillation patients with ACS/PCI
Eur Heart J Aug 2014
2014 Executive Summary AHA/ACC/HRS Atrial Fibrillation Guidelines
Terapia Anticoagulante e Terapia Antiaggregante … dopo SCA e PCI
• Non esiste una controindicazione all’impiego dei NAO nei pazi enticon patologia atero-trombotica coronarica o che si sottopo ngono aprocedure di rivascolarizzazione per via percutanea
• Non e’ stata documentata una reale interazione sfavorevole i ntermini di efficacia e sicurezza tra i NAO e gli Antiaggreganti (Asa eClopidogrel); e’ riportato solo un incremento dei sanguina mentinell’associare i NAO alla doppia antiaggregazione
CONCLUSIONS & TAKE HOME MESSAGES - 1
nell’associare i NAO alla doppia antiaggregazione
• Il parere degli esperti nei Documenti di Consenso e nelle Lin eeGuida propende per una limitazione all’impiego protratto di unatriplice terapia antitrombotica
• 1 solo studio randomizzato “valida” l’associazione di Warfari n eClopidogrel; i sottogruppi dei 3 principali studi sui NAO “li indicanopiù sicuri” di Warfarin anche in corso di terapia antiaggreg ante
• Non e’ ancora noto l’impatto sulle problematiche trombotic he edemorragiche di questi pazienti in ogni associazione che preve da inuovi farmaci antipiastrinici e i nuovi anticoagulanti ora li
TERAPIA ANTITROMBOTICA
PAZIENTE CON FIBRILLAZIONE ATRIALE
E “ACS/STABLE CAD” SOTTOPOSTO A PCI
…Prima della PCI … Post PCI …
Single Therapy
CHA2DS2-VASc Score
HAS-BLED Score
Clinical Setting : ACS o Stable CAD
Timing (1 - 6 > 12 mesi)
CONCLUSIONS & TAKE HOME MESSAGES - 2
CHA2DS2-VASc Score
HAS-BLED Score
…Terapia lifelong
N (OAC)
Double Therapy
Triple Therapy
ASA + Clopidogrel+ Warfarin
Clopidogrel+
WarfarinSingle Therapy
Clinical Setting : ACS o Stable CAD
PCI Bare Metal Stent o Drug Eluting Stent
N (OAC)
INR 2-2,5
ASA o Clopidogrel+
NAO
as short aspossible
Singolo Paziente
AREE GRIGIE…
Double Therapy (ASA o Clopidogrel) + NAO…
Triple Therapy (ASA + Clopidogrel) + NAO…
CONCLUSIONS & TAKE HOME MESSAGES - 3
Good Daily Clinical Practice
Trials Clinici
Linee Guida
Singolo Paziente
“Buon Senso Clinico”
Polipatologia
Nuovi Inibitori P2Y 12 (Prasugrel e Ticagrelor) + Warfarin e/o NAO…
BMS o Nuovi DES …
Se SCA in NAO si prosegue NAO o si passa a Warfarin …
Anziani Fragili, con IRC avanzata e FA e/o SCA …
GRAZIE PER GRAZIE PER
L’ATTENZIONEL’ATTENZIONE