Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients
Kenneth Jamerson, M.D., Michael A. Weber, M.D., George L. Bakris, M.D., Björn Dahlöf, M.D., Bertram Pitt, M.D., Victor Shi, M.D., Allen Hester, Ph.D., Jitendra Gupte, M.S., Marjorie Gatlin, M.D., Eric J. Velazquez, M.D., for the ACCOMPLISH Trial Investigators
Background The optimal combination drug therapy for hypertensionis not established, although current U.S. guidelines recommendinclusion of a diuretic. We hypothesized that treatment withthe combination of an angiotensin-converting–enzyme (ACE)inhibitor and a dihydropyridine calcium-channel blocker wouldbe more effective in reducing the rate of cardiovascular eventsthan treatment with an ACE inhibitor plus a thiazide diuretic.
Methods In a randomized, double-blind trial, we assigned 11,506patients with hypertension who were at high risk for cardiovascularevents to receive treatment with either benazepril plus amlodipineor benazepril plus hydrochlorothiazide. The primary end pointwas the composite of death from cardiovascular causes, nonfatalmyocardial infarction, nonfatal stroke, hospitalization forangina, resuscitation after sudden cardiac arrest, and coronaryrevascularization.
Results The baseline characteristics of the two groups weresimilar. The trial was terminated early after a mean follow-upof 36 months, when the boundary of the prespecified stoppingrule was exceeded. Mean blood pressures after dose adjustmentwere 131.6/73.3 mm Hg in the benazepril–amlodipine groupand 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazidegroup. There were 552 primary-outcome events in the benazepril–amlodipinegroup (9.6%) and 679 in the benazepril–hydrochlorothiazidegroup (11.8%), representing an absolute risk reduction withbenazepril–amlodipine therapy of 2.2% and a relative riskreduction of 19.6% (hazard ratio, 0.80, 95% confidence interval[CI], 0.72 to 0.90; P<0.001). For the secondary end pointof death from cardiovascular causes, nonfatal myocardial infarction,and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67to 0.92; P=0.002). Rates of adverse events were consistent withthose observed from clinical experience with the study drugs.
Conclusions The benazepril–amlodipine combination wassuperior to the benazepril–hydrochlorothiazide combinationin reducing cardiovascular events in patients with hypertensionwho were at high risk for such events. (ClinicalTrials.gov number,NCT00170950
[ClinicalTrials.gov]
.)
Source Information
From the University of Michigan Health System, Ann Arbor (K.J., B.P.); the State University of New York Downstate Medical College, Brooklyn (M.A.W.); the University of Chicago Pritzker School of Medicine, Chicago (G.L.B.); Sahlgrenska University Hospital, Gothenburg, Sweden (B.D.); Novartis Pharmaceuticals, East Hanover, NJ (V.S., A.H., J.G., M.G.); and Duke University School of Medicine, Durham, NC (E.J.V.).
Address reprint requests to Dr. Jamerson at the Division of Cardiovascular Medicine, University of Michigan Health System, 24 Frank Lloyd Wright Dr., Lobby M, Ann Arbor, MI 48106, or at emarshal{at}umich.edu.
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