1. Combination Therapy for Hypertension Summary and Comment by Harlan M. Krumholz, MD, SM Published in Journal Watch Cardiology December 3, 2008Journal Watch Cardiology In the ACCOMPLISH trial, a calcium channel blocker was more effective than a thiazide diuretic was when paired with an ACE inhibitor. CopyrightCopyright © 2008. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

2. Covering Jamerson K et al. for the ACCOMPLISH trial investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008 Dec 4; 359:2417. Chobanian AV. Does it matter how hypertension is controlled? N Engl J Med 2008 Dec 4; 359:2485. CopyrightCopyright © 2008. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

3. Background Clinicians are keenly interested in identifying the best approach to pharmacologic treatment of hypertension, found in 73 million people in the U.S. and 1 billion in the world. In the manufacturer-sponsored Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, researchers compared two combination treatments: an ACE inhibitor plus either a thiazide diuretic or a calcium channel blocker (CCB). All participants had hypertension in addition to impaired renal function, peripheral artery disease, LV hypertrophy, diabetes, a history of coronary events, or a combination of these conditions. The primary endpoint was a composite of cardiovascular death and cardiovascular events. CopyrightCopyright © 2008. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

4. The Research The investigators randomized 5744 individuals (mean age, 68; 40% women) to benazepril-amlodipine and 5762 to benazepril- hydrochlorothiazide. At enrollment, 97% of patients were being treated for hypertension, and 75% were taking medications from ≥2 drug classes. Mean systolic blood pressure was 145 mm Hg at baseline and, after dose adjustment, declined to 133 mm Hg in the benazepril- amlodipine group and to 132 mm Hg in the benazepril- hydrochlorothiazide group. CopyrightCopyright © 2008. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

5. The Research At a mean of 30 months of follow-up, a primary endpoint had occurred in 552 (9.6%) patients in the benazepril-amlodipine group and 679 (11.8%) in the benazepril-hydrochlorothiazide group, a relative risk reduction of 19.8% (P<0.001), and the trial was terminated early. Event rates per 1000 patient-years were 32.3 in the benazepril- amlodipine group and 39.7 in the benazepril-hydrochlorothiazide group. Safety results were similar in the two groups. CopyrightCopyright © 2008. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

6. Comment In this trial, benazepril plus amlodipine produced better outcomes than did benazepril plus hydrochlorothiazide, despite similar efficacy in reducing blood pressure. These findings challenge the preference for thiazide diuretics contained in recommendations from some organizations, as well as the notion that all thiazide diuretics are the same. The author of a related editorial does not endorse a particular strategy. This study is likely to engender some controversy about the best approach to hypertension control in high-risk patients. CopyrightCopyright © 2008. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society

7. About Journal Watch Journal Watch helps physicians and allied heath professionals save time and stay informed by providing brief, clearly written, clinically focused perspectives on the medical developments that affect practice. Journal Watch is an independent, trustworthy source, from the publishers of the New England Journal of Medicine. These slides were derived from Journal Watch Cardiology.Journal Watch Cardiology The best way to stay informed with Journal Watch, is through our alerts. To sign up, visit the My Alerts page.My Alerts page CopyrightCopyright © 2008. Massachusetts Medical Society. All rights reserved.Massachusetts Medical Society