Cardiovascular Drug Selection in Pregnancy

8/20/2019 Cardiovascular Drug Selection in Pregnancy

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Cardiovascular DrugSelection in Pregnancy

Dr Orchid Barua

D-CARD Student



United States of America Food and Drugadministration ( FDA )drugs in pregnancycategories :

Category A : adequate and well-controlled studies have ailed to showris! to the etus in "regnancy#Category B : ani$al studies have ailed to show ris! to the etus %utthere are no adequate and well-controlled studies in hu$ans#Category C : ani$al studies have shown ris! to the etus& and there areno adequate and well-controlled studies in hu$ans& %ut "otential %ene'ts$ay warrant use o the drug in "regnant wo$en des"ite "otential ris!s#

Category D : there is evidence o hu$an etal ris! %ased on data ro$research or clinical e "erience& %ut "otential %ene'ts $ay warrant use othe drug in "regnant wo$en des"ite "otential ris!s#Category X : studies in ani$als or hu$ans have shown etala%nor$alities and or there is evidence o hu$an etal ris! %ased onresearch or clinical e "erience& and the ris!s involved in use o the drug in"regnant wo$en clearly outweigh "otential %ene'ts#



ANTIHYP !T NSI" A# NTS INP! #NANCY

*eterogenous entity: "re-e isting hy"ertension& gestationalhy"ertension and "re-ecla$"sia(so$eti$es classi'ed into $ildand severe)+o %ene't o treating $ild to $oderatehy"ertension(, ./ /$$*g)- acc to 0SCSevere *1+(2 ./ /$$*g) is an e$ergency requiring

hos"itali3ation4ethyldo"a 5Drug o choice ollowed %y 6a%etalol& CCB is 7AC0 and ARB are contraindicated



Drugs

Contraindicated

tensin$

con%ertingen&yme

'AC (in)i*itors

angiotensinrecep

tor*+oc, ers

-A!Bs.

%erapami+

di+tia&em

reserpine

nitroprussid

e



Acute Blood Pressure Loweringfor Severe Hypertension

SBP 8 9/ $$*g or DBP 8 / $$*gtreat$ent goal is reduction in 4AP %y ,7 ; over$inutes to hours with hal hourly $onitoring o BP andheart rate



Source:Cardiac Drugs in Pregnancy 0ditors: <aren Sliwa = >ohn Anthony



1reat$ent o 4ild *y"ertension&and 4aintenance oAntihy"ertensive 0?ect

no certainty on the value o treating@*O states e "licitly in its guideline o 4 o "re-ecla$"sia and ecla"sia that no reco$$endation can %e$ade



Source:Cardiac Drugs in Pregnancy 0ditors: <aren Sliwa = >ohn Anthony



Methyldopa

Supplied: 7 &/01 & // $g ta%& also availa%le a%roaDosage: 7 / $g twice daily& increasing i needed to $a# g daily

Ad%erse e2ects 3 include orthostatic hy"otension&sedation& di33iness& atigue& Coo$%s "ositivity de"ression

occurs in 77 ;#Caution3 Avoid methyldopa after parturition because thedrug may precipitate or worsen depression



Beta%loc!er

$ost co$$on %eta-%loc!ers used during "regnancy arelabetalol, atenolol, and pindolol

advantages over $ethyldo"ado not usually cause orthostatic hy"otension& so$nolence& or signi'cantde"ressiongiven once daily

Ad%erse e2ects :etal or neonatal %radycardia

"re$ature or "rolonged la%ordelayed s"ontaneous %reathing in the new%orn& $ainly o%served with userarely neonatal hy"oglyce$ia

EFR and low in ant %irth weight (atenolol)



4a*eta+o+ 'FDA$C(

Bloc!s Beta5a+p)a6 & so vasodialationacute short-ter$ $anage$ent o severe resistanthy"ertension Gust %e ore la%or or during deliveryi v la%etolol $ore e?ective than hydrala3ine or$ethyldo"a as-

BP lowering e?ect is $ore "redicta%le&causes less tachycardiaa""ears to cause less etal distress than hydrala3ine#

Avoid in asth$atics



Adverse efects o labetalol Chances o orthostatic hy"otension

EFR(incidence 7.;)

"erioral nu$%ness& tingling& and itching o the scal"& and rarely a lu"us-li!e illness& a lichenoid rasha rare association is retro"lacental he$orrhage (6indhei$er and <at3

HI )# Also, a rare but li e-threatening complication is acute hepaticnecrosis (Clar!e et al# HH/ )#

T)ese serious side e2ects are not caused *y ot)er *eta$adrenergic *+oc,ers7

8etopro+o+' /& // $g) JDA-CDosage: / $g twice daily& $a # 7// $g



Hydra+a&ine 'FDA$C(

"ure arteriolar vasodilatorcauses reKe tachycardia and sodiu$ and water retentionvery use ul when a $odest dose is co$%ined with a lowdose BB& i#e# atenolol / $g daily& or with $ethyldo"achronic use li$ited %y etal thro$%ocyto"enia(rare)&

di33iness& "ostural hy"otension& a lu"us syndro$e&"al"itations& and ede$aDosage: 7 $g twice daily& increasing to three ti$es daily$a # // $g daily %e ore the addition o a %eta- %loc!ingdrug



CCB: +i edi"ine(JDA 5C)0 tensive e "erience %ut 6ac!s Controlled clinical trial in acutehy"ertensive e$ergencies ul$inating "reecla$"sia resistantsevere *1+Jor acute severe *1+: - /$g ca"sules orally swallowed& re"eat inecessary every L/$in with /$g& to a $a 7/$g daygiven in late "regnancy M accelerated severe hy"ertensionresulted in an average all in %lood "ressure o 79 7/ $$*gwithin 7/ $in o oral dosingJor $ild *1+ $aintenance o Anti*1+ e?ect: ni edi"ine slowrelease L/- 7/$g day as once daily dose%est co$%ined with short-ter$ use o atenolol 7 5 / $g daily or"indolol $g daily to "revent "ea!ing o BP during last tri$ester#



Caution : 1heoretical ears o serious interactions with$agnesiu$ sul"hate& have not %een realised in "ractice*eadache&Best avoided i 1achycardia(do not use i *R8 7/ $in) coronaryartery disease or ' ed cardiac out"ut valvular disease$ay inhi%it la%or$anu acturer advises to avoid %e ore wee! 7/ always %alanceris! with %ene'tuse only i other treat$ent o"tions are not indicated or have

ailed#



9t)er drugs as anti)ypertensi%eDia&o:ide3rarely used& and $ay cause a ra"iddro" in BP#Sodium nitroprusside

last resort treat$ent in CE setting withintra-arterial BP $onitoring#

etal cyanide "oisoning& should ideally

only %e used "ost"artu$Diuretics3

"otential har$ ul e?ects owing to thereduction o "las$a volu$e& cardiacout"ut& and utero"lacental "er usion& sodiuretics are not generally indicated$ay cause neonatal thro$%ocyto"enia(rarely)

ACE Inhibitors

are contraindicated during "regnancy#

4ay adversely a?ect etal and neonatal BP control and renalunction#

$ay cause s!ull de ects and oligohydra$nios

teratogenic in ani$als

associated with a high incidence o intrauterine death#

Acute renal ailure with catastro"hic consequences has %eein neonates o $others given AC0 inhi%itors in the third tri



9t)er drugs

MagnesiumSul ate$ild and transientlowering o %lood"ressure#$ost use ul agent

or the "reventiono sei3uresassociated withsevere"reecla$"sia

Aspirin

Patients with C<D& D4& autoi$$une disease& or chronic *1+ are at high ris! o develo"in"reecla$"sia and as"irin is advisa%le#

Dosage . 5I $g once daily ro$ 7th wee! until the %a%y is %orn#

Patients with $ore than one $oderate ris! actor

'rst "regnancy&aged 8N/ years&

"regnancy interval 2 / years&B4 8L !g $ 7 at 'rst visit&$ulti"le "regnancy& or

a$ily history o "reecla$"siaare at ris! or develo"ing "reecla$"sia and as"irin . 5I $g once daily is advised#



D!U# TH !APY F9! H A!TFAI4U!

S"ectru$ o C D leading to heart ailure or "ul$onaryede$a in "regnancy:4itral stenosis($ost co$$on) and rarely other *DSyste$ic hy"ertension associated with "reecla$"siaPul$onary hy"ertensionPeri"artu$ cardio$yo"athy



1a%le : Reco$$endations or the $anage$ent o cardio$yo"athies and heart ailure in"regnancy(0SC Fuidelines on the 4anage$ent o Cardiovascular Disease DuringPregnancy (Regit3- agrose! et al# 7/ )!ecommendations 4e%e+ of e%idenceC4ASS IAnticoagulation is reco$$ended in "atients with intracardiacthro$%us detected %y i$aging or with evidence o syste$ice$%olis$#

A

@o$en with *J during "regnancy should %e treated according tocurrent guidelines or non-"regnant "atients& res"ectingcontraindications or so$e drugs in Pregnancy

B

1hera"eutic anticoagulation with 64@* or vita$in < antagonistsaccording tostage o "regnancy is reco$$ended or "atients with atrial'%rillation#

C

C4ASS IIaDelivery should %e "er or$ed with -%loc!er "rotection inwo$en with *C4#

C

-%loc!ers should %e considered in all "atients with *C4 and$ore than $ild6 O1O or $a i$al wall thic!ness 2 $$ to "revent sudden

"ul$onary Congestion

C



8itra+ stenosis in Pregnancy4S aggravates during "regnancyco$"lications :"ul$onary ede$a or atrialtachyarrhyth$ias atrial '%rillation Kutter$ust decrease their activity and co$$enced on a %eta-%loc!ereg# 4eto"rolol M- urose$ide (res"onse to thera"y Q. ;)

aggressive $edical thera"y ails: nterventional and surgicalo"tions

nterventional "rocedures should %e delayed until 75 N wee!s("eriod o organogenesis)%est de erred to %etween 79 and L/ wee!sthe "rocedure o choice : Percutaneous $itral valvulo"lasty



BBCornerstone o treat$ent in$edical 4 o 4S in "regnancyBB "revents Pul$onary ede$ain 4S with "regnancy$ar!ed clinical i$"rove$ent

when resting heart rate reducedro$ a $ean o I95.I %eats $in 1itrate BB according to *R andsy$"to$

Digo:in 'FDA $

no value in the 4 o "ul$onary ede$a caused %y "ure $itrastenosis

s$all role in hy"ertensive heart ailure& DC4 or other condiassociated with "oor 6 systolic unction

+o teratogenic or untoward adverse etal e?ects

/ ; reduction in seru$ levels in the "regnant& as o""osed tonon"regnant



T)ia&ides

short-ter$ thia3ide diuretic thera"y over a ew days is indicatedor sy$"to$atic relie along with o ygen and $or"hine until 4S

can %e corrected %y P14B or %y surgery

rarely cause etal or neonatal Gaundice or thro$%ocyto"enia& %uttheir use is Gusti'a%le or the treat$ent o "ul$onary ede$a andhy"ertension associated with "reecla$"sia (always co$"are ris!with %ene'ts)

Furosemide

contraindicated %ecause causes etal

%ut can %e used or "ul$onary ede$a in the la

"regnancy and in the "uer"eriu$ to $anage li e-thre

Diuretics in *J



notro"es and veso"ressors:other interventions should %e used initially to $anagehy"otension&

e#g# ad$inistration o intravenous Kuids"lacing the "atient in the le t lateral decu%itus "osition to "reventco$"ression o the in erior vena cava %y the gravid uterus#

a%ove ails use vaso"ressor thera"y"aucity o clinical studies with no consensus a%out which isthe %est vaso"ressor+ore"ine"hrine can %e used as the 'rst-line vasoactive agentwho ail to res"ond to early aggressive volu$e resuscitation#do"a$ine and levosi$endan can %e used as well



Vasodilators :

AC0 inhi%itorscontraindicated at all stages o "regnancy#

*ydrala3ine$ay %e used in the third tri$ester o "regnancy i a terloadreduction is dee$ed necessary or the $anage$ent o heart

ailureto icity and teratogenic e?ects in ani$al studies& so $ust %eavoided during the 'rst tri$ester#



Summery of 8edica+ management ofc)ronic )eart fai+ure in pregnancy

Drug;c+ass Purpose Comments

DiureticsJurose$ide Fenerally reserved or

treat$ent o "ul$onaryede$aEse o lowest "ossi%le dose

Can result in utero"l*y"o"er usionJDA class C

Digo in +ot considered 'rst-linethera"y

or heart ailure in non-"regnant Patients+o i$"rove$ent in $ortality

Fenerally consideredEse ul in treat$ent o

"ersistent sy$"to$s&des"ite standard therJDA class C

"asodi+ators*ydrala3ine

Co$$only used oralantihy"ertensive agent in"regnancyCan %e su%stituted or AC0inhi%itor during "regnancy

De$onstrated e cachy"ertensionRis! o hy"otensionAvoid large or "reci"decreases in %lood

JDA class C



A+dosteroneantagonistsS"ironolactone&0"leronon

e

Prolong survival in selected

heart ailure "atients

+ot routinely used in

"regnancy+o data to su""ort sa"regnancyJDA class D

@ar arin Ris! %ene't ratio needs to %ediscussed with the "atient ortreat$ent and "ro"hylacticanticoagulation in severe le tventricular Dys unction

Jirst tri$ester teratogDosing is co$"licate"regnancyJDA class (contraindicated)



Fig7 1reat$ent o heart

ailure in

wo$enwithcardio$yo"athyaccording tostage o"regnancySource:CardiacDrugs inPregnancy 0ditors:<aren Sliwa = >ohnAnthony

+on"regnant

• Accordingtostandard

heartailure

0arly"regnancy

• Diuretics• *ydrala3in

e• Beta

6atePregnancy

• Diuretics• *ydrala3in

e• Beta



Peripartum ardiomyopathy addition o %ro$ocri"tine to standard heart ailure thera"y

$ay %e %ene'cial in "atients with acute onset PPC4(*il'!er-<leiner et al#7//. )A "roo -o -conce"t "ilot study o PPC4 "atients withseverely reduced 6 0J& diagnosed within $onth odelivery& showed a $ar!ed i$"rove$ent in systolic

unction and reduced $ortality in "atients treated with%ro$ocri"tine 7# $g twice daily or 7 wee!s& ollowed %y7# $g daily or N wee!s& co$"ared with "atients receivingstandard care with AC0-inhi%itors and %eta-%loc!ers onlyRC1 currently underway



Drugs in Coronary Artery Disease andArrhyth$ias:



!lycoprotein ""b#"""a $eceptor Antagonistsvery li$ited e "erienceOnly a ew case re"orts are docu$ented in which"atients received % a rece"tor antagonists a tercoronary stenting or an ACS during "regnancy# n these

cases& no co$"lications or adverse etal outco$es werenoted (Chow et al# HHI )#$ight %e considered or use in high-ris! clinicalcircu$stances& %ut& in general& should %e avoided&es"ecially shortly %e ore delivery#

ANTIA!!HYTH8ICS IN P! #NANCY



ANTIA!!HYTH8ICS IN P! #NANCY



Ta*+e :Drugs orarrhyth$ias in"regnancy



Anticoagulation in Pregnancy

*e"arin 1he $ost co$$on adverse e?ects o%served includeosteo"orosis and thro$%ocyto"enia in the $other& i thedrug is used or longer "eriods (Regit3- agrose! et al#7/ )#

signi'cantly less requent in low $olecular weighthe"arin(64@*) is used#JDA 5B



<arfarinJDA category D

Ne=er anticoagu+ants3Dana"aroid (with a he"arin li!e action) JDA category B

Can %e used in *e"arin induced thro$%ocyto"enia

Da%igatran& and the Jactor a-inhi%itors Rivaro a%an& A"i a%an and

Jonda"arinu not reco$$ended in "regnant "atient!ecent antip+ate+ets 3"rasugrel& ticagrelor& %ivalirudin and glyco"rotein % a inhi%itorsnot reco$$ended during "regnancy %ecause o insu cient sa ety data

Cardiovascular Drug Selection in Pregnancy

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