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Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients
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| AUTHORS |
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Kenneth A Jamerson, Michael A Weber, George L Bakris, Bjorn Dahlof, Bertram Pitt, Victor Shi, Allen Hester, Jitendra Gupte, Marjorie Gatlin, Eric J Velazquez, The ACCOMPLISH Trial Investigators
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| PUBLICATION INFORMATION |
Journal Name: The New England Journal of Medicine
Volume: 359(23)
Pages: 2417-28
Date Published: 12/04/2008
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| ABSTRACT/REVIEW |
What were the researchers trying to learn in this study? They wanted to know if combining an ACE inhibitor and a calcium channel blocker would be more effective in reducing the rate of cardiovascular events in high risk patients with hypertension than treatment with an ACE inhibitor plus a diuretic.
Specifically they compared the combination of the ACE inhibitor benazepril (beh-NAZE-eh-pril) and the calcium channel blocker amlodipine (am-LOW-di-peen) with the combination of benazepril and a diuretic, hydrochlorothiazide (high-dro-klor-oh-THI-a-zide).
ACE inhibitors are a class of drugs that decreases the effects of chemicals that tighten the blood vessels so that blood flows better. A calcium channel blocker relaxes the blood vessels. Diuretics cause the kidneys to eliminate water and salt from the body through the urine, thus reducing blood pressure.
What did they find? The study was stopped early after a follow-up of 36 months because the benefits of benazepril-amlodipine combination were clearly better than those of the benazepril and diuretic combination.
The patients in the benazepril-amlodipine group lowered their average blood pressure to 131.6/73.3 mmHg compared with 132.5/74.4 mmHg for the diuretic group. This difference in reduction is considered statistically significant. Target blood pressure of 140/90 mmHg was achieved in 75.4% in the benazepril-amlodipine group compared to 72.4% of patients in the benazepril-hydrochlorothiazide group.
There were 552 cardiovascular events (9.6%) in the benazepril-amlodipine group and 679 events (11.8%) in the benazepril-hydrochlorothiazide group. This represents a 19.6% relative reduction in the risk of cardiovascular death, stroke, myocardial infarction (heart attack), coronary revascularization, unstable angina and resuscitation from death in the benazepril-amlodipine group compared with the benazepril-hydrochlorothiazide group. It represents a 2.2% reduction in the absolute risk of experiencing one of these events.
Rates of adverse events including dizziness, peripheral edema (swelling), and dry cough did not differ significantly between the two groups.
Who was studied? Patients from 5 countries including the U.S., Sweden, Norway, Denmark and Finland representing 548 centers were included in the study. The average age of the patients was 68.4 and 39.5% were women. Of the patients, about 50% were obese, 60% had diabetes, 23% had a history of heart attack, 6% had kidney disease and about 36% had previously had a revascularization procedure. About 97% were previously being treated for hypertension. Only 37.3% had adequately controlled hypertension.
How was the study done? There were 11,506 patients randomly assigned to the two groups, 5,744 patients to the benazepril-amlodipine group and 5,762 to the benazepril-hydrochlorothiazide group. The patients were randomly assigned to receive one or the other combination of drugs.
What did researchers know before starting this study? The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. These researchers proposed that treatment with the combination of an angiotensin-converting-enzyme (ACE) inhibitor and a calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a diuretic.
Why did they do it? The researchers thought that combinations that do not include diuretics should be considered in the guidelines. They wanted to test their theory that the combination of an ACE Inhibitor and a calcium channel blocker would be more effective in treating this population of patients than the ACE inhibitor and the diuretic. The sponsor of the study also wanted to test its combination amlodipine and valsartan medication for controlling high blood pressure.
What did the researchers say their study results mean? These researchers concluded that this study shows that combination therapy with benazepril and amlodipine results both in excellent blood-pressure control and also in a clear benefit with respect to cardiovascular outcomes.
Editor's note: This study was funded by Novartis, which makes Exforge®, a combination calcium channel blocker (valsartan) and amlodipine (ACE inhibitor), such as that used in the patients studied.
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