Overview and comparison of three important hypertension guidelines

Recently,newdatafromhypertensiontrialsincludingnewdrugclasseshavebeensurging, giving rise to changes in the management of patients with arterial hypertension, and to modificationsofpracticeguidelines.Newertrialshavealsoquestionedtheefficacyofcurrently recommendeddrugsandtreatmentstrategiesfrequentlyusedintheclinicalsetting. In the following we give an overview and comparison of three important hypertension guidelinesinuse. The guidelines on hypertension issued by the World Health Organization (WHO) and International Society of Hypertension (ISH) in 2003 are directed towards a global audience includinglessdevelopedsocietieswithlimitedresourcesthatmustbemosteffectivelyutilised. In a global capacity assessment the WHO surveyed 167 countries and found that in 61% of those,nonationalguidelineswereavailable,in45%healthprofessionalswerenottrainedto manage hypertension and in 25% antihypertensive agents were not affordable. In primary healthcare basic equipment for the management of hypertension was not available in 8% of the countries and antihypertensive drugs were missing in 12% of the countries. When resources are limited the WHO recommends giving lowrisk patients lower priority for treatment.AccordingtotheWHOthefirstchoiceoftherapyonthebasisofcomparativetrial data, availability and cost for the majority of patients without a compelling indication for another drug class should be a low dose of a diuretic. In most places, diuretics are the cheapestandthereforemostcosteffectiveoption. ThepurposeoftheSeventhReportoftheJointNationalCommitteeonPrevention,Detection, Evaluation,andTreatmentofHighBloodPressure(JNC7)publishedbytheU.S.NationalHeart, Lung and Blood is to synthesise the available scientific evidence and offer guidance to busy primarycarecliniciansintheUnitedStates.Itisavailableintwoversions;theExpressversion which contains succinct evidencebased recommendations, and the full report with comprehensive justification and rationale. One special aim of JNC 7 was to simplify the classificationofbloodpressure(BP).TheseguidelinesareadjustedtoanAmericanpopulation andthusincludealsorecommendationsforAfricanAmericans,whodemonstrateasomewhat reduced BP response to monotherapy with betablockers (BBs), angiotensin converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) compared to diuretics or calcium channel blockers (CCBs). JNC 7 recommends that patients with systolic BP between 120139 mmHg or diastolic BP between 8089 mmHg should be considered prehypertensive andrequirehealthpromotinglifestylemodificationstopreventcardiovasculardisease(CVD). Thiazidetypediureticsshouldbetheinitialdrugtherapyformostpatients,eitheraloneorin combination with other drug classes, but certain highrisk conditions are compelling indicationsforotherdrugclasses.Anewupdateoftheseguidelinesisexpectedtobereleased thissummer. In2003,theEuropeanSocietyofHypertension(ESH)andtheEuropeanSocietyofCardiology (ESC)publishedthefirstissueoftheirguidelinesonthemanagementofarterialhypertension. Before,bothsocietieshadendorsedtheWHO/ISHguidelines,butduetothefact,thatthese guidelinesaddresscountrieswidelyvaryingintheextentoftheirhealthcareandavailabilityof economic resource, and thus containing diagnostic and therapeutic recommendations that

maybenottotallyappropriateforEuropeancountries,theESHESCdecidedtoproducetheir ownguidelinesadjustedtothesituationinEurope.Duetotheavailabilityofnewconsiderable additional evidence on important issues related to diagnostic and treatment approaches to hypertensionthepreviousguidelineswereupdatedin2007.Toaddressanumberofimportant studiesonhypertension(e.g.ADVANCE,LIFE,ONTARGET)publishedinthe2yearsafterwards, areappraisalofthe2007guidelineswaspublishedin2009. Areweallreachingthesamegoalsinbloodpressuremanagement? InternationalguidelineshavealladoptedalmostthesameBPtargetgoalsoftherapy,basedon findings on risk reduction of cardiovascular outcomes associated with blood pressure reduction and life style modifications. Blood pressure lowering reduces cardiovascular and renal morbidity and mortality. Therefore, guidelines recommend achieving a BP target of <140/90mmHginhypertensivepatientswithlowtomoderaterisk,whileforthoseathighand veryhighrisk(i.e. diabetesorrenaldisease),BPistargetedata lowerlevel<130/80mmHg. There are minor differences in the classification of arterial hypertension in the different guidelines(seetable1). Table1.ClassificationofArterialHypertension BloodPressureClassification
Optimal Normal HighNormal Grade1Hypertension(mild) Subgroup:Borderline Grade2Hypertension(moderate) Grade3Hypertension(severe) IsolatedSystolicHypertension Subgroup:Borderline PreHypertension Stage1 Stage2

SystolicBP WHOISH ESHESC

<120 <130 130139 140159 140149 160179 180 140 140149 <120 120129 130139 140159 160179 180 140

JCN7
<120

DiastolicBP WHOISH ESHESC JCN7

<80 <85 8589 9099 9094 100109 110 <90 <90 <80 8084 8589 9099 100109 110 <90 <80

120139 140159 160

8089 9099 100

Theinitialapproach Initial pharmacological approach in hypertension should be individualised and based on BP levels and cardiovascular risk stratification, rather than on a drug class alone. The ESCESH 2007guidelinesand2009reappraisal,aswellasthe2003WHOrecommendations,suggestthe useofanyoftheantihypertensivedrugsapproved(CA,ARB,ACEI,BBandDiuretics)forinitial treatmentofarterialhypertension.TheAmericanguidelines(JNC7)recommendthiazidetype diuretics as firstline therapy, either alone or in combination with other drug classes, but do not reject other options as initial therapy. The role of thiazides in the American guidelines could be due to the elevated number of African American individuals with hypertension, populationinwhichthiazidetypediureticshaveprovenanunmatchedeffectinpreventingthe cardiovascularcomplicationsofhypertension. Profileofapproveddrugsforhypertensiontherapy Guidelines recommend the use of calcium antagonists (CA), diuretics, angiotensin receptor blockers(ARBs),angiotensinconvertingenzymeinhibitors(ACEIs)andbetablockers(BBs)for

the treatment of hypertension, either alone or in combination. The most recently updated guidelines,theESCESH2009reappraisalofthe2007guidelines,haveincludeddataregarding newdrugs,suchasdirectrenininhibitors(aliskiren),whichhaveproveninclinicaltrialstobe effective in lowering SBP and DBP in hypertensive patients when given in monotherapy at a singledailydose,andtobesafewhengivenincombinationwiththiazidediuretics,CAs,ACEIs orARBs. BBs have shown a trend towards an increased risk of myocardial infarction (MI) and heart failure(HF)insometrials(e.g.ASCOT,LIFE,HAPPHY,INVEST).However,allguidelinescontinue to recommend them as an effective option, as evidence has shown similar effects with BBs thanwithotheragents,inpreventingcardiovasculareventsandHF,andahigherefficacythan other drugs in patients with a recent coronary event. Compelling data on the benefits in BP loweringachievedwithACEIsandARBs,andsuggestionsofcardiovascularprotectionbeyond BP control, have earned these agents a strong recommendation in all guidelines, for the managementofhypertension,especiallyinhighandveryhighriskpatients.AgentssuchasCAs have shown an additional advantage in preventing stroke, as well as an effective BP control profile, supporting the basis of their recommendation in the current guidelines. Table 2 summarisesrecommendationsonpreferredagentsbasedonunderlyingcomorbidities. Table 2. Guideline recommendations for hypertension therapy in patients with compelling indications Indication WHOISH2003 ESHESC2007/2009 JNC72004 Elderly with isolated Diuretic,DHPCCB Diuretics,CA Thiazidetype systolichypertension diuretics alone or in combination with one of the other classes (ACEIs, ARBs, BBs,CAs) PostMI ACEI,BB BB,ACEI,ARB BB, ACEI, Anti aldosteroneagents Left Ventricular ACEI ACEI ACEI,BB,diuretic Dysfunction Congestive Heart Diuretic, BB, Diuretics, BB, ACEI, Thiazidetype Failure Spironolactone ARB, Anti diuretic, BB, ACEI, aldosteroneagents ARB, Anti aldosteroneagents Poststroke ACEI + diuretic, Any BP lowering Thiazidetype Diuretic agent diuretic,ACEI RenalDisease ACEI,ARB ACEI,ARB ACEI,ARB Left Ventricular ARB ACEI,CA,ARB ACEI,diuretic,ARB Hypertrophy Peripheral Artery n/a CA Anyclassofdrugscan Disease be used in most patients Asymptomatic n/a CA,ACEI n/a atherosclerosis Tachyarrhythmias/ n/a BB BB fibrillation ESRD/proteinuria n/a ACEI, ARB, loop n/a diuretics

n/a BB,CA Thiazide diuretic, BB, ACEI,ARB,CA DHPCCB = Dihydropyridine calcium channelblockers; BB = Blockers; ACEI = Angiotensin convertingenzymeinhibitors;ARB=Angiotensinreceptorblockers;CA=Calciumantagonists; MI=Myocardialinfarction Guidelinerecommendationsinspecialpopulations Current guidelines have established therapeutic combinations based on proven therapeutic efficacy in reduction of cardiovascular risk in highrisk patients, and in special population subgroups.ARBsandACEIsarethemostfrequentlymentioned,andtheirefficacyinhighand veryhighriskpatients(diabetes,diabeticandnondiabeticnephropathy,overtrenaldisease, cerebrovasculardiseaseandheartfailure)supportstheirroleincurrentrecommendations. Incerebrovasculardisease,evidencefromtrialsalsosuggestthatthebenefitlargelydepends on BP lowering per se, and therefore guidelines such as the ESCESH suggest the use of any approved drug, and rational combinations, for the treatment of patients after a stroke. In patientswithcoronaryheartdisease,theyallsupporttheuseofBB,ARBsorACEIs,duetotrial datasuggestingreductionintheincidenceofrecurrentMIanddeathinpatientspostMI. Recently,patientsovertheageof80andchildrenandadolescentshavestartedtoplayamore importantroleinhypertensionguidelines.Allavailableguidelineshighlighttheimportanceof treatinghighbloodpressureinthesepatientswiththeuseofanyoftheavailabledrugs,but makeacallaswellfortheurgeofstrongerevidenceinthesespecialpopulations. CombinationTherapy European and international guidelines strongly recommend the use of combination therapy. The 2007 ESHESC guidelines recommend the combination of two drugs to be considered as initial treatment whenever hypertensive patients have a high initial BP or are classified as beingathighorveryhighcardiovascularrisk.TheWHOandJNC7sharethisrecommendation aswell,andspecifytheneedofasecondagentinstage2hypertensionorforpatientswhose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolicBPgoalandinpatientswithcompellingindications. Even though all guidelines strongly recommend combination therapy, only the ESCESH guidelines offer detailed data on the evidence supporting the synergistic efficacy of drug combinations. Figure 1 shows the combinations recommended for dual therapy of hypertensionaccordingtotheESCESH2007guidelines. Figure 1. Evidencebased recommended combination of drug classes for treatment of hypertension.

Microalbuminuria Anginapectoris Diabetes

n/a n/a n/a

ACEI,ARB BB,CA ACEI,ARB

 ACEI and diuretics have shown a greater effect on recurrent stroke and on BP lowering in patients with type 2 diabetes, and this has been associated with a reduced incidence of diabetesrelated complications. This combination also offers an excellent tolerability profile withfewsideeffects.Ithasbeenproventobesafeintheelderly,effectivelyreducingBPand loweringtheratesofCVoutcomes.AsforARBs,theyhavebeenrecommendedbyguidelines in combination with CA (RENAAL study) and diuretics (LIFE study), but evidence does not support the combination with ACEIs. The ESCESH 2009 reappraisal states that the combination,notrecommendedin2007,hasstillconflictingdataregardingfurtherreductions in cardiovascular or renal events in highrisk patients. ARBs also offer a great amount of evidence suggesting effective BP reduction and higher rates of BP control in a variety of hypertensioncategories,excellenttolerabilityprofile,andprotectionagainstsubclinicalorgan damagewhencombinedwithaCAoradiuretic. Guidelines in the management of arterial hypertension focus on the importance to individualised therapy, and recommend appropriate drug selection mainly based on risk stratification.Theyhaveslightlydifferentapproachesontherapyinitiation,butthesupporting evidenceofferedallconvergesonthe samepillarsofantihypertensivetreatment,suggesting theuseofcombinationtherapytotargetBPcontrolandreducecardiovascularriskinpatients athighrisk. References 1. ManciaG,DeBackerG,DominiczakA,etal.2007ESHESCPracticeGuidelinesforthe Management of Arterial Hypertension: ESHESC Task Force on the Management of ArterialHypertension.JournalofHypertension2007;25:17511762. 2. Mancia G, Laurent S, AgabitiRosei, et al. Reappraisal of European guidelines on hypertensionmanagement:aEuropeanSocietyofHypertensionTaskForcedocument. BloodPress2009;18(6):308347.

3. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. Journal of Hypertension 2003;21:1983 1992. 4. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension2003;42(6):12061252.