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14/7/2015 Reninangiotensinsysteminhibitioninthetreatmentofhypertension

http://www.uptodate.com/contents/reninangiotensinsysteminhibitioninthetreatmentofhypertension?topicKey=NEPH%2F3815&elapsedTimeMs=4&sour 1/13

OfficialreprintfromUpToDate www.uptodate.com2015UpToDate

AuthorsJohannesFEMann,MDKarlFHilgers,MD

SectionEditorsGeorgeLBakris,MDNormanMKaplan,MD

DeputyEditorJohnPForman,MD,MSc

Reninangiotensinsysteminhibitioninthetreatmentofhypertension

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Jun2015.|Thistopiclastupdated:Oct08,2014.

INTRODUCTIONInhibitorsofthereninangiotensinsystem(RAS),includingangiotensinconvertingenzyme(ACE)inhibitors,angiotensinIIreceptorblockers(ARBs),anddirectrenininhibitorsarecommonlyusedinthetreatmentofhypertension.TheroleoftheRASinhypertensionandtheuseofspecificinhibitorsofthissystemtotreathypertensionwillbereviewedhere.

TheuseofRASinhibitorsinpatientswithkidneydiseaseanddiabetesarediscussedseparately.(See"Choiceofdrugtherapyinprimary(essential)hypertension:Recommendations"and"Antihypertensivetherapyandprogressionofnondiabeticchronickidneydiseaseinadults"and"Treatmentofhypertensioninpatientswithdiabetesmellitus"and"Treatmentofdiabeticnephropathy".)

Theimportanceoflocal(ie,tissue)RASactivityinlowreninhypertensionandtheeffectsofangiotensinIIontheheartarepresentedelsewhere.(See"Lowreninprimary(essential)hypertension"and"ActionsofangiotensinIIontheheart".)

ANGIOTENSINCONVERTINGENZYMEINHIBITORSSincetheintroductionofcaptoprilin1977[1],angiotensinconvertingenzyme(ACE)inhibitorshavebecomewidelyusedforthetreatmentofhypertensionandthreeofitsmajorcomplications:acutemyocardialinfarction[2],congestiveheartfailure[3],andchronickidneydisease.Fiftyto60percentofCaucasianpatientshaveagoodresponsetomonotherapywithACEinhibitors,aresponseratesimilartootherfirstlineantihypertensivedrugs[4].ACEinhibitorshavetheadditionaladvantagesofhavingamorefavorablesideeffectprofilethansympatheticblockers,betablockers,anddiuretics[5],andofproducingmoreregressionofleftventricularhypertrophythanbetablockers[6].(See"Clinicalimplicationsandtreatmentofleftventricularhypertrophyinhypertension",sectionon'Choiceofdrugs'.)

Guidelinesissuedin2009bytheEuropeanSocietyofHypertension[7],andin2011byNICE(NationalInstituteforHealthandClinicalExcellenceofGreatBritain)[8],recommendtheuseofanACEinhibitororangiotensinIIreceptorblocker(ARB)inyoungerandnonblackpatients[9].However,thisrecommendationisbaseduponrelativelysmallcrossovertrials[10].

SpecificindicationsforuseThereareanumberofsettingsinwhichACEinhibitorsaretheantihypertensivedrugsofchoicebecauseofpossiblebenefitsinadditiontoloweringthebloodpressure.(See"Choiceofdrugtherapyinprimary(essential)hypertension:Recommendations",sectionon'Indicationsforspecificdrugs'.)

Theseinclude:

Heartfailurewithreducedejectionfraction(HFrEF)[3].(See"ACEinhibitorsinheartfailureduetosystolicdysfunction:Therapeuticuse"and"Useofbetablockersandivabradineinheartfailurewithreducedejectionfraction"and"Useofdiureticsinpatientswithheartfailure"and"Useofmineralocorticoidreceptorantagonistsinsystolicheartfailure".)

Proteinuricchronickidneydisease,bothdiabeticandnondiabetic[11].(See"Antihypertensivetherapyandprogressionofnondiabeticchronickidneydiseaseinadults"and"Moderatelyincreasedalbuminuria(microalbuminuria)intype1diabetesmellitus"and"Moderatelyincreasedalbuminuria(microalbuminuria)intype2diabetesmellitus"and"Treatmentofhypertensioninpatientswithdiabetesmellitus".)



AntihypertensiveresponseThedeclineinbloodpressureseenwithACEinhibitorsappearstobeprimarilyduetodecreasedformationofangiotensinII,butdecreaseddegradationofkininscouldcontributebybothdirectvasodilationandincreasingtheproductionofvasodilatorprostaglandins[12].

BlackpatientsmaybelesssensitivethanwhitepatientstoACEinhibitorsasmonotherapyforhypertension(figure1)[13].AlthoughACEinhibitorsarerelativelyineffectiveasmonotherapyinblacks,theadditionofevenalowdoseofathiazidediuretictoanACEinhibitorleadstoafallinbloodpressurethatiscomparabletothatseeninwhitepatients[14].(See"Treatmentofhypertensioninblacks".)

TheutilityofACEinhibitorswithdiureticsisnotlimitedtoblackpatientssincethesedrugshaveasynergisticeffect,attaininggoalbloodpressureinupto85percentofpatientswithmildhypertension[14].TheantihypertensiveresponsetodiureticsisoftenlimitedbythehypovolemiainducedincreaseinreninreleaseandsubsequentangiotensinIIproduction[15]thiseffectispreventedbyconvertingenzymeinhibition,leadingtoamoreprominentreductioninbloodpressure.(See"Useofthiazidediureticsinpatientswithprimary(essential)hypertension".)Forsimilarreasons,dietarysodiumrestrictioncanalsoenhancetheresponsetoanACEinhibitor[16].(See"Saltintake,saltrestriction,andprimary(essential)hypertension",sectionon'Responsetoantihypertensivedrugs'.)

ACEinhibitorsminimizesomeofthemetabolicchangesinducedbydiuretictherapy.Hypokalemia,forexample,islessprominentbecausethereductioninangiotensinIIformationinducedbytheACEinhibitorleadstodecreasedsecretionofaldosterone.ACEinhibitorsalsodonotinduceglucoseintolerance,hyperlipidemia,orhyperuricemia,mayincreaseinsulinsensitivity,andmayminimizeorpreventdiureticinducedelevationsinserumglucose,cholesterolanduricacidlevels[17].

Apartfromdiuretics,calciumchannelblockerscanbeusedeffectivelywithACEinhibitors,and,asshownintheACCOMPLISHtrial,mayhaveclinicaladvantagesoverdiureticswhenachievedbloodpressureissimilar.CombinationofanACEinhibitorwithabetablockermaybelessusefulbecauseofinferiorantihypertensiveactivitycomparedwithotherACEinhibitorcombinations[18].Thisrelativelackofefficacymaybedueinparttosimilarmechanismsofaction,asangiotensinIIformationandreninsecretionarerespectivelyreduced.(See"Choiceofdrugtherapyinprimary(essential)hypertension:Recommendations",sectionon'ACCOMPLISHtrial'.)

DoseAswithotherantihypertensiveagents,properdosecanminimizetheincidenceofsideeffects(table1).TominimizetheriskoffirstdosehypotensionduetoanabruptdeclineinangiotensinIIlevels,thepatientshouldnotbevolumedepleted.Theinitialdosecanbereducedbyonehalfinelderlypatientsorthosewithheartfailurewhoareathigherriskforhypotension.SideeffectsotherthanthoserelatedtohypotensioncanoccurwithACEinhibitors,themostcommonbeingcough[19],lesscommonlyhyperkalemia,andrarelyangioedema[20].ACEinhibitorsarecontraindicatedduringpregnancy[21].(See"MajorsideeffectsofangiotensinconvertingenzymeinhibitorsandangiotensinIIreceptorblockers".)

ThedurationofactionvarieswithdifferentACEinhibitors.SomeACEinhibitorscanbegivenoncedaily(eg,trandolapril,lisinopril,andbenazepril).Theuseoflongeractingagentsoncedailyshouldimprovepatientcompliance,reducecosts,maintainsmoothercontrol,andensurethattheabruptriseinpressureuponawakeningintheearlymorningisblunted,hopefullytherebyreducingtheincidenceofseriouscardiovasculareventsatthistime.

Aftertheinitiationoftherapy,thepatientshouldbereexaminedinafewweekstoallowthefullantihypertensiveeffecttooccur.Ifthereisnoorlittlefallinbloodpressurewithanadequatedose,thedrugcanbestoppedanddifferentclassofdrugstarted,aconceptcalled"sequentialmonotherapy."Alternatively,anotherdrugmaybeadded,suchasacalciumchannelblocker.(See"Choiceofdrugtherapyinprimary(essential)hypertension:Recommendations",sectionon'Sequentialmonotherapy'.)

Afteramyocardialinfarctioninmostpatients,particularlythosewithheartfailureorreducedsystolicfunction[2].(See"Angiotensinconvertingenzymeinhibitorsandreceptorblockersinacutemyocardialinfarction:Recommendationsforuse".)



Ifthepatient'sbloodpressureisreducedbytheACEinhibitorbutthegoalpressureisnotachieved,thedosecanbegraduallyincreasedtothemaximumlevelsnotedinthetable(table1).However,theadditionofaseconddrugfromadifferentclasswillprovidemuchgreaterantihypertensiveeffect[22].

Inpatientswithextensiveatherosclerosisorrenalinsufficiencywhoaremorelikelytohaverenovascularstenoses,arepeatplasmacreatinineconcentrationshouldbeobtainedwithinonetotwoweekstoensurethatrenalperfusionhasbeenmaintained.However,amodestandnonprogressiveincreaseintheplasmacreatinineinsuchpatientsshouldnotpromptdiscontinuationoftherapy.(See"RenaleffectsofACEinhibitorsinhypertension",sectionon'Renovascularhypertension'.)

ANGIOTENSINIIRECEPTORBLOCKERSAngiotensinIIreceptorblockers(ARBs)interferewiththereninangiotensinsystembyimpairingthebindingofangiotensinIItotheAT1receptoronthecellmembrane,therebyinhibitingtheactionofangiotensinII[23].BlockadeoftheactionofangiotensinIIleadstoelevationsinplasmalevelsofrenin,angiotensinI,andangiotensinII.However,thisbuildupofprecursorsdoesnotoverwhelmthereceptorblockade,asevidencedbyapersistentfallinbothbloodpressureandplasmaaldosteronelevels[24].

DifferencesbetweenACEinhibitorsandARBsTherearesubstantialpharmacologicaldifferencesintheactionsofangiotensinconvertingenzyme(ACE)inhibitorsandARBs,butfewclinicaldifferenceshavebeendocumented.Atleastthreefactorsmaycontributetothepharmacologicaldifferences(figure2):

EfficacyanddoseTheARBshaveaneffectsimilartothatseenwithmonotherapywithotherantihypertensivedrugs(table1)[26].However,severalstudieshaveshownthatlosartan,whengivenoncedaily,doesnotcontrolbloodpressuretothesamemagnitudeasotherARBs(irbesartan,telmisartan,candesartan,andvalsartan)[2730].Ontheotherhand,losartanproducesaslightfallinplasmauricacidthatdoesnotoccurwiththeotherARBs,aneffectthatisduetoenhanceduricacidexcretion[31].Thisappearstobemediatedatleastinpartbydirectinhibitionoftheproximalurateanionexchangerthatisresponsibleforuratereabsorption[32].

TheantihypertensiveefficacyofARBsappearstoberoughlyequivalenttothatoftheACEinhibitors.Ametaanalysisof61studiesthatdirectlycomparedangiotensinIIreceptorblockersandACEinhibitorsreportednodifferenceintheantihypertensiveeffectsoftheseagents[26].

Inaddition,theeffectsofARBsandACEinhibitorsoncardiovasculareventsappearsimilar.TheONTARGETtrialcomparedtelmisartan(80mg/day),ramipril(10mg/day),andcombinationtherapy(80+10mg/day)withbothagentsin25,620patientswithvasculardiseaseordiabetes[33].Theprimaryoutcomewasdeathfromcardiovascularcauses,myocardialinfarction,stroke,orhospitalizationforheartfailure.Achievedmeanbloodpressurewaslowerinpatientswhoreceivedtelmisartancomparedwithramipril(by0.9/0.6mmHg)andinpatientswhoreceivedbothagentscomparedwithramipril(2.4/1.4mmHg).Thecardiovascularoutcomesweresimilarinallthreegroups,whilecoughwasmorecommonwithramiprilandbothhyperkalemiaandacutekidneyinjuryweremorecommonwithcombinedtherapy.(See"MajorsideeffectsofangiotensinconvertingenzymeinhibitorsandangiotensinIIreceptorblockers".)

Inaddition,ametaanalysisofninetrialsand11,007patientsthatdirectlycomparedACEinhibitorswithARBsin

Angiotensinconvertingenzymeisakininase.Thus,inhibitingthisenzyme,whichnormallydegradesbradykinin,withanACEinhibitorleadstoincreasedkininlevels,aneffectnotseenwithanARB.ThisislikelyresponsibleforthecoughthatmaybeseenwithACEinhibitors(butnotwithARBs),althoughhighbradykininlevelsmayalsoprovideadditionalvasodilationandotherbenefitsnotobservedwithARBs.

BydecreasingangiotensinIIproduction,ACEinhibitorsreducetheeffectofbothAT1andAT2receptorsonlytheformerareinhibitedbytheARBs.

Intheheart,kidney,andperhapsthebloodvessels,theproductionofangiotensinIImaybecatalyzedbyenzymesotherthanangiotensinconvertingenzyme,suchaschymase[25].TheeffectoftheangiotensinIIproducedbythisreactioncanbeinhibitedbytheARBsbutnotbyACEinhibitors.However,theroleofthesenonACEenzymesforthegenerationofangiotensinIIinvivo,ifany,isuncertain.



hypertensivepatientsfoundsimilarratesofallcausemortalityandcardiovascularmortality[34].Incontrast,drugwithdrawalduetoadverseeventswassignificantlymorefrequentwithACEinhibitors(oneadditionalwithdrawalfromtherapyforevery55patientstreatedwithACEinhibitorsoverfouryears),mostlyduetodrycough.Thus,ARBsareareasonablealternativetoACEinhibitortherapyinhypertensivepatients.

Aswithotheragentsthatinhibitthereninangiotensinsystem,theefficacyofARBsisenhancedbyconcomitantadministrationoflowdosesofadiuretic[35],andbyareductionindietarysodiumintake.AswithACEinhibitors,ARBsappeartominimizethehypokalemiaandhyperuricemiainducedbydiuretictherapy[35].(See"Saltintake,saltrestriction,andprimary(essential)hypertension",sectionon'Responsetoantihypertensivedrugs'.)

SIDEEFFECTSBothangiotensinconvertingenzyme(ACE)inhibitorsandangiotensinIIreceptorblockers(ARBs)aregenerallywelltolerated.CoughandangioedemaarelesscommonwithARBs[33].BothACEinhibitorsandARBsarecontraindicatedinpregnancy.Theseissuesarediscussedindetailseparately.(See"MajorsideeffectsofangiotensinconvertingenzymeinhibitorsandangiotensinIIreceptorblockers"and"Angiotensinconvertingenzymeinhibitorsandreceptorblockersinpregnancy".)

ACEinhibitorsplusARBsAseparateissueisthesideeffectsassociatedwithcombinedACEinhibitor/ARBtherapycomparedwitheitherdrugalone.TheONTARGETtrialcitedaboveofhighriskpatients[33,36]foundasignificantincreaseinadverseeffects(includingapossibleincreaseinmortality)withcombinedtherapycomparedwithanACEinhibitoralone.Asaresult,combinedtherapyisnotrecommendedforthetreatmentofhypertension.

Thedatasupportingadverseeffectsandthepossibleroleofcombinedtherapytoslowprogressioninpatientswithproteinuricchronickidneydiseasearediscussedelsewhere.(See"MajorsideeffectsofangiotensinconvertingenzymeinhibitorsandangiotensinIIreceptorblockers",sectionon'CombinationofACEinhibitorsandARBs'and"Antihypertensivetherapyandprogressionofnondiabeticchronickidneydiseaseinadults",sectionon'CombinationofACEinhibitorsandARBs'.)

DIRECTRENININHIBITORSThefirsteffectiveoraldirectrenininhibitor,aliskiren,becameavailableintheUnitedStatesinMarch2007.Aliskirenlowersbloodpressuretoadegreecomparabletomostotheragents[37].Anumberofstudieshaveevaluatedthebloodpressureloweringeffectofaliskirenincombinationwithotherantihypertensivedrugs[3740].Inonereport,thecombinationofmaximumdosesofaliskirenandvalsartandecreasedbloodpressuremorethanmaximumdosesofeitheragentalonebutnotmorethanwouldbeexpectedwithdualtherapyusingdrugsfromdifferentclasses[41].Aliskiren,aswithotherinhibitorsofthereninangiotensinsystem,shouldnotbeusedinpregnancy.

IntheAVOIDtrial,aliskirenpluslosartanwasassociatedwithasignificant20percentgreaterreductioninproteinuriacomparedwithlosartanaloneinpatientswithtype2diabetesandnephropathy,intheabsenceofasignificantlygreatereffectonbloodpressure[42].However,thiseffectonproteinuriadidnottranslateintoaclinicalbenefit.IntheALTITUDEtrial,8600patientswithtype2diabetesandkidneydiseasealreadytakingeitheranangiotensinconvertingenzyme(ACE)inhibitororangiotensinIIreceptorblocker(ARB)wererandomlyassignedtoadditionaltherapywithaliskirenorplacebo[43].TheALTITUDEtrialwasstoppedearlybecauseoffutility(nobenefitontheprimarycardiovascularandrenaloutcomes)andbecausealiskirentherapyproducedanonsignificantlyhigherrateofadverseevents(ie,nonfatalstroke,hypotension).TheALTITUDEtrialisdiscussedindetailelsewhere.(See"Treatmentofdiabeticnephropathy",sectionon'Aliskirenplusangiotensininhibition'.)

TheeffectofaliskirenonprogressionofatheroscleroticcoronaryarterydiseaseinpatientswithcontrolledhypertensionwasexaminedintheAliskirenQuantitativeAtherosclerosisRegressionIntravascularUltrasoundStudy(AQUARIUS)[44].Inthistrial,613patientswithasystolicbloodpressurebetween125and139mmHg(mostofwhomweretreatedwithantihypertensivemedications)andtwoothercardiovascularriskfactorswererandomlyassignedtoaliskiren(300mg/day)orplacebo.After18months,theatheroscleroticburdenandprogressionofatherosclerosis(measuredbycoronaryintravascularultrasound)wassimilarbetweenthegroups.Inasecondaryanalysisbaseduponasmallnumberofevents,aliskirenappearedtoreducetherateofcardiovascularevents.However,thisanalysisexcludeddiabeticpatientswhoweretreatedwithangiotensininhibitors(approximately15percentofthestudypopulation),assuchpatientswereremovedfromthestudyafter



publicationoftheALTITUDEtrial[45].Inaddition,adverseeventsweremorecommonwithaliskiren.

AnincreasedriskofhyperkalemiawhenaliskireniscombinedwithACEinhibitorsorARBshasbeendescribedintheALTITUDEtrialandinotherstudies[43,46].Thus,aliskirenshouldnotbecombinedwithACEinhibitorsorARBs[47].

SUMMARYANDRECOMMENDATIONS

Inhibitorsofthereninangiotensinsystem,includingangiotensinconvertingenzyme(ACE)inhibitors,angiotensinIIreceptorblockers(ARBs),anddirectrenininhibitorsarecommonlyusedinthetreatmentofhypertension.(See'Introduction'above.)

ThereareanumberofsettingsinwhichACEinhibitorsaretheantihypertensivedrugsofchoicebecauseofpossiblebenefitsinadditiontoloweringthebloodpressure(see'Specificindicationsforuse'above):

Heartfailurewithreducedejectionfraction(HFrEF)

Proteinuricchronickidneydisease,bothdiabeticandnondiabetic

Afteramyocardialinfarctioninmostpatients,particularlythosewithheartfailureorreducedsystolicfunction

ProperdoseofACEinhibitorscanminimizetheincidenceofsideeffects(table1).ThedurationofactionvarieswithdifferentACEinhibitors.SomeACEinhibitorscanbegivenoncedaily(eg,trandolapril,lisinopril,andbenazepril).(See'Dose'above.)

TherearepharmacologicaldifferencesintheactionsofACEinhibitorsandARBs.ExceptforthecoughassociatedwithACEinhibitors,thesepharmacologicaldifferencesarenotassociatedwithclinicallymeaningfuldifferencesintherapeuticeffects.Atleastthreefactorsmaycontributetothepharmacologicaldifferences(figure2)(see'DifferencesbetweenACEinhibitorsandARBs'above):

Angiotensinconvertingenzymeisakininase.Thus,inhibitingthisenzyme,whichnormallydegradesbradykinin,withanACEinhibitorleadstoincreasedkininlevels,aneffectnotseenwithanARB.ThisislikelyresponsibleforthecoughthatmaybeseenwithACEinhibitors(butnotwithARBs),althoughhighbradykininlevelsmayalsoprovideadditionalvasodilationandotherbenefitsnotobservedwithARBs.

BydecreasingangiotensinIIproduction,ACEinhibitorsreducetheeffectofbothAT1andAT2receptorsonlytheformerareinhibitedbytheARBs.

Intheheart,kidney,andperhapsthebloodvessels,theproductionofangiotensinIImaybecatalyzedbyenzymesotherthanangiotensinconvertingenzyme,suchaschymase.TheeffectoftheangiotensinIIproducedbythisreactioncanbeinhibitedbytheARBsbutnotbyACEinhibitors.

TheARBshaveaneffectsimilartothatseenwithmonotherapywithotherantihypertensivedrugs,includingACEinhibitors(table1).

TheantihypertensiveeffectofbothACEinhibitorsandARBsisenhancedbyconcomitantadministrationoflowdosesofadiuretic,andbyareductionindietarysodiumintake.Bothdrugsalsoappeartominimizethehypokalemiaandhyperuricemiainducedbydiuretictherapy.(See'Dose'aboveand'Efficacyanddose'aboveand"Saltintake,saltrestriction,andprimary(essential)hypertension",sectionon'Responsetoantihypertensivedrugs'.)

BothACEinhibitorsandARBsaregenerallywelltolerated.Sideeffectsotherthanthoserelatedtohypotensioncanoccurwithbothdrugs,includinghyperkalemiaandrarelyangioedema,aswellasacutekidneyinjuryinpatientswithloweffectivearterialbloodvolume(eg,diarrhea,vomiting,andheartfailure).CoughisacommonsideeffectofACEinhibitors.ACEinhibitorsandARBsarecontraindicatedduring



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Topic3815Version11.0



GRAPHICS

Antihypertensiveresponsetodifferentdrugsinblacks

Responseratestosingledrugtherapyforhypertensioninblacksovertheageof60years.Thehighestresponsewasseenwithdiltiazemandhydrochlorothiazide(HCTZ)andthelowestwithcaptopril.Aresponsewasdefinedasadiastolicpressurebelow90mmHgattheendofthetitrationphaseandbelow95mmHgatoneyear.Thepatternofresponsewassimilarbutthesuccessrateforeachdrugwasreducedby5to15percentifgoaldiastolicpressurewerelessthan90mmHgatoneyear.Therewerebetween42and53patientsineachgroup.

Datafrom:MatersonBJ,RedaDJ,CushmanWC.DepartmentofveteransAffairssingledrugtherapyofhypertensionstudy.Revisedfiguresandnewdata.DepartmentofVeteransAffairsCooperativeStudyGrouponAntihypertensiveAgents.AmJHypertens19958:189.

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http://www.uptodate.com/contents/reninangiotensinsysteminhibitioninthetreatmentofhypertension?topicKey=NEPH%2F3815&elapsedTimeMs=4&sou 10/13

Angiotensinconvertingenzyme(ACE)inhibitorsandreceptorantagonistsfortreatmentofadultswithhypertension

Drug UStradenameGeneric

preparationavailableinUS

Usualoraldailydoserange(adult)mg*

ACEinhibitors

Benazepril Lotensin Yes 20to80

Captopril Capoten(onlyavailableinUSasgenericpreparation)

Yes 25to150intwoorthreedivideddoses

Cilazapril Inhibace(Canadiantradename)

No 2.5to5

Enalapril Vasotec Yes 10to40

Fosinopril Monopril(onlyavailableinUSasgenericpreparation)

Yes 20to80

Lisinopril Prinivil ,Zestril Yes 10to40

Moexipril Univasc Yes 7.5to30

Perindopril Aceon Yes 4to8

Quinapril Accupril Yes 10to40

Ramipril Altace Yes 2.5to20

Trandolapril Mavik Yes 2to4

AngiotensinIIreceptorantagonists

Azilsartan Edarbi No 80

Candesartan Atacand No 16to32

Eprosartan Teveten Yes 600to800

Ibresartan Avapro Yes 150to300

Losartan Cozaar Yes 50to100

Olmesartan Benicar No 20to40

Telmisartan Micardis No 40to80

Valsartan Diovan No 80to320

*Thedoserangereferstothetreatmentofpatientswithhypertension.Dosesaslowasonehalforonequarterthelowerdoseshownmaybeusedinitiallyinhighriskpatientssuchasthosewithheartfailure,significantrenalinsufficiency,hyponatremia,intravascularvolumedepletion,orreceivingconcurrenttreatmentwithadiuretic.Thedrugmaybegivenindivideddosesatthehigherdoselevels.Adjustaccordingtobloodpressureresponseatpeakandtroughbloodlevels.



NotavailableinUS.

Datafrom:LexicompOnline.Copyright19782015Lexicomp,Inc.AllRightsReserved.




ComparisonoftheactionsofangiotensinconvertingenzymeinhibitorsandangiotensinIIreceptorblockers

ACE:angiotensinconvertingenzymeACEI:angiotensinconvertingenzymeinhibitorARB:angiotensinIIreceptorblocker.




Disclosures:JohannesFEMann,MDGrant/Research/ClinicalTrialSupport:NovoNordisk[Diabetes(Liraglutide)]Vifor[Dialysis(Ironhydroxide)]Clegene[Dialysis(Sotatercept)].Speaker'sBureau:Amgen[Anemia(Darbepoetin)Roche[Anemia(Methoxypolyethyleneglycolepoetinbeta)Novartis[Hypertension(Valsartan)]Bruan[Dialysis(dialysisdevices)]Fresenius[Dialysis(dialysisdevices)].Consultant/AdvisoryBoards:NovoNordisk[Diabetes(Liraglutide)]Relypsa[Kbinder(Patiromer)]Abbvie[CKD(Paricalcitol)]Bayer[Hypertension(Diuretics)].KarlFHilgers,MDGrant/Research/ClinicalTrialSupport:AstellasNovartis[Kidneytransplantation(Tacrolimus,cyclosporine,everolimus)].GeorgeLBakris,MDGrant/Research/ClinicalTrialSupport:MedtronicRelypsa[Hypertension,hyperkalemia].Consultant/AdvisoryBoards:MedtronicRelypsaBayerNovartisDSIBoehringerIngelheimLexiconJanssenAstraZenecaKona[Diabetes,hyperkalemia,resistanthypertension(Canagliflozin,dapagliflozin,empagliflozin)].NormanMKaplan,MDNothingtodisclose.JohnPForman,MD,MScNothingtodisclose.Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.Conflictofinterestpolicy

Disclosures

ieca y ara ii

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