Angiotensin II antagonists for hypertension are there differ

Angiotensin II Antagonists for Hypertension: Are There Differences in Ef?cacy?

Paul R.Conlin,J.David Spence,Bryan Williams,Arthur B.Ribeiro,Ikuo Saito,Claude Benedict, and Antonius M.G.Bunt

We compared the antihypertensive ef?cacy of available drugs in the new angiotensin-II-antagonist(AIIA)class.The antihypertensive

ef?cacy of losartan,valsartan,irbesartan,and candesartan was evaluated from randomized controlled trials(RCT)by performing a metaanalysis of43published RCT.These trials involved AIIA compared with placebo,other antihypertensive classes,and direct comparisons between AIIA.A weighted-average for diastolic and systolic blood pressure reduction with AIIA monotherapy,dose titration,and with addition of low-dose hydrochlorothiazide(HCTZ)were calculated.Weighted-average responder rates were also determined.The metaanalysis assessed a total of11,281patients.The absolute weighted-average reductions in diastolic(8.2to8.9mm Hg)and systolic(10.4to11.8mm Hg)blood pressure reductions(not placebo-corrected)for AIIA monotherapy were comparable for all AIIA.Responder rates for AIIA monotherapy were48% to55%.Dose titration resulted in slightly greater blood pressure reduction and an increase in responder rates to53%to63%.AIIA/hydrochloro-thiazide combinations produced substantially greater reduction in systolic(16.1to20.6mm Hg) and diastolic(9.9to13.6mm Hg)blood pressure reductions than AIIA monotherapy and responder rates for AIIA/HCTZ combinations were56%to 70%.This comprehensive analysis shows comparable antihypertensive ef?cacy within the AIIA class,a near-?at AIIA-dose response when titrating from starting to maximum recommended dose,and substantial potentiation of the antihypertensive effect with addition of HCTZ. Am J Hypertens2000;13:418–426?2000American Journal of Hypertension,Ltd.

KEY WORDS:Hypertension,randomized controlled trials,ef?cacy,review,angiotensin-II-antagonists.

A new class of antihypertensive drugs—an-

giotensin II antagonists(AIIA)—has

emerged during the past5years.These

agents speci?cally and selectively antago-nize the effects of angiotensin II(AII)at the angioten-sin type1(AT1)receptor.Prior clinical experience with angiotensin-converting enzyme inhibitors (ACE-I)suggested that this new class of drugs would be similarly effective for the treatment of hyperten-sion.

Received February26,1999.Accepted September17,1999. From the Endocrinology-Hypertension Division(PR),Brigham and Women’s Hospital and Harvard Medical School(JS),Boston, Massachusetts;Siebens-Drake/Robarts Research Institute,Univer-sity of Western Ontario,London,Ontario;Cardiovascular Research Institute(BW),University of Leicester,Leicester,United Kingdom; Nephrology Division(AR),UNIFESP-EPM,Sa?o Paulo,Brasil; Health Center(IS),Keio University,Tokyo,Japan;University of Texas Medical School(CB),Houston,Texas;and Merck&Co.Inc. (AMGB),Whitehouse Station,New Jersey.

This work was supported by grants from National Institutes of Health(HL57173)and Merck and Company,Inc.

Address correspondence and reprint requests to Paul R.Conlin, MD,Endocrinology-Hypertension Division,Brigham and Women’s Hospital,221Longwood Avenue,Boston,MA02115;e-mail: pconlin@271465c18bd63186bcebbcd0

AJH2000;13:418–426

?2000by the American Journal of Hypertension,Ltd.0895-7061/00/$20.00 Published by Elsevier Science,Inc.PII S0895-7061(99)00237-X

Losartan was the?rst of the AIIA to be approved for clinical use in hypertension,in1994.Since then,three other agents,valsartan,irbesartan,and candesartan, have been introduced for clinical use;many others are at various stages of development.Differences in the pharmacokinetic(PK)and pharmacodynamic(PD)pa-rameters of these agents,such as gastrointestinal ab-sorption,protein binding,volume of distribution,con-version of prodrug or active parent to active metabolite,oral bioavailability,competitive or non-competitive antagonism of AII at AT1receptors,re-ceptor binding af?nity,and elimination half-life,have been described.1–7

These differences have been cited as potentially im-portant causes of differential clinical ef?cacy within the AIIA class,particularly with regard to the magni-tude and duration of the antihypertensive response.In this regard,some recent publications have suggested differences in antihypertensive ef?cacy when AIIA were directly compared to each other in patients with hypertension.8–11This question of ef?cacy is poten-tially very important because if there are real and clinically meaningful differences in antihypertensive ef?cacy within the AIIA class,physicians would need to be aware of such differences to optimize therapeutic decisionmaking.

Independent interpretation of the available clinical data is confounded by the following problems:small trials,often conducted by the pharmaceutical manu-facturer with a study design potentially set up in its favor;differences in methodology in describing the blood pressure(BP)reduction that hamper or pre-clude comparisons across studies;and a lack of suf?-ciently large,well-designed,independent head-to-head comparative studies.In the absence of optimal studies,an alternative way to objectively assess the antihypertensive ef?cacy of AIIA is to pool all of the existing randomized clinical trial(RCT)data and con-duct a metaanalysis.We report the results of such an analysis and,in so doing,describe the antihyperten-sive ef?cacy of currently available AIIA from studies where these agents were compared with other classes of antihypertensive therapy and with each other.

MATERIALS AND METHODS

Data Sources This analysis examines the antihyper-tensive ef?cacy of four currently available AIIA—lo-sartan,valsartan,irbesartan,and candesartan—using Medline and Current Contents,through October1998, as sources of data.

Types of Data Three categories of peer-reviewed data were considered:randomized,double blind, plac …… 此处隐藏：35184字，全部文档内容请下载后查看。喜欢就下载吧 ……