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Amlodipine/benazepril reduces adverse cardiovascular outcomes, death in patients with hypertension

Friday, April 04 2008 | Comments

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What's This? By Nancy Stanley

A fixed-dose, single-pill combination of a calcium channel blocker and an ACE inhibitor, amlodipine besylate/benazepril hydrochloride, appears to significantly reduce cardiovascular morbidity and mortality relative to a combination of a diuretic and benazepril in high-risk patients with hypertension, according to interim data from the ACCOMPLISH trial.

The primary objective of the study was to determine if amlodipine/benazepril would confer a 15% reduction in cardiovascular morbidity and mortality in high-risk patients with hypertension when compared with hydrochlorothiazide and benazepril as initial combination therapy.

The trial included more than 11,000 high-risk patients with hypertension and was designed to challenge the current guidelines for initial therapy with a diuretic-based therapy. The patients were randomized to receive amlodipine/benazepril or hydrochlorothiazide/benazepril in titrating doses, and they could begin taking additional antihypertensive agents at 3 months.

In October 2007, the Data and Safety Monitoring Board recommended the termination of the trial because the prespecified efficacy boundary was crossed with 60% of the expected trial information.

The primary endpoint was cardiovascular morbidity and mortality, which was defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, coronary revascularization, and resuscitated sudden death.

Dr. Kenneth Jamerson, lead researcher, noted that most of the patients received aggressive medical management prior to study entry, although only 37.5% of the patients' hypertension was considered controlled (<140/90 mm Hg).

Results showed that patients who received amlodipine/benazepril had a 20% relative risk reduction in the primary endpoint relative to the patients who received hydrochlorothiazide/benazepril after an average 39 months of follow-up (HR, 0.80; 95% CI, 0.71-0.90; P=.0002).

The trends of some components of the primary endpoint also favored amlodipine/benazepril. Specifically, the risk of cardiovascular death, stroke, and MI was also significantly reduced by 20% with amlodipine/benazepril relative to hydrochlorothiazide/benazepril (P=.007).

Approximately 80% of patients in both treatment arms achieved BP control after a mean 30-month follow-up. In addition, amlodipine/benazepril significantly reduced systolic BP relative to hydrochlorothiazide/benazepril (between-group difference, 0.7 mm Hg; P<.05). The difference between the cohorts in the reduction in diastolic BP was also significant.

"ACCOMPLISH has achieved exceptional BP control with combination therapy, and offer[s] a new option to use with patients who are taking antihypertensive medication and continue to have risk," Dr. Jamerson noted.

"The results provide compelling information that combination therapy with ACE inhibitor/calcium channel blocker should be initial therapy and challenge current diuretic-based guidelines," he concluded.

Novartis AG funded this study. (Presentation 407-2.)

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