Clinical

Calcium channel blocker improves cardioprotection in hypertensive diabetics

NEW YORK (Reuters Health) - For patients with diabetes and hypertension, combining an ACE inhibitor with a calcium channel blocker provides better protection against cardiovascular events than combining an ACE inhibitor with a diuretic, data from the ACCOMPLISH trial shows.

In fact, the difference was so marked that the trial was stopped early, its researchers report in the Journal of the American College of Cardiology for June 29.

"This represents a difference in strategy from that recommended by older traditional guidelines like JNC 7, which preferred the combination of a RAS (renin-angiotensin system) blocker with a thiazide diuretic," lead author Dr. Michael A. Weber commented in an e-mail to Reuters Health. "In other words, this should be a major change in the basic approach to treating hypertension in people with diabetes."

In the trial, some 11,500 hypertensive subjects at high risk for cardiovascular events were randomized to treatment with benazepril plus amlodipine or to benazepril plus hydrochlorothiazide. The current article focuses on the nearly 7,000 participants who had diabetes. About 41% in each treatment arm required at least one additional drug (of another type) to control their hypertension.

Dr. Weber at SUNY Downstate College of Medicine, New York and colleagues report that among the diabetic patients, the mean blood pressure achieved was 131.5/72.6 mmHg with benazepril plus amlodipine and 132.7/73.7 mmHg with benazepril plus hydrochlorothiazide. The difference between the two groups was not statistically significant.

However, the difference in occurrence of cardiovascular events over 30 months was significant in the diabetics. (The same was true in the overall study population, and the monitoring committee recommended that the trial be terminated when the boundary of the prespecified stopping condition was exceeded.)

The primary endpoint of the trial was a composite of cardiovascular death, MI, stroke, hospitalization for angina, resuscitated arrest, and coronary revascularization. During follow-up among the subjects with diabetes there were 307 such primary events in the amlodipine group versus 383 in the hydrochlorothiazide group, yielding a hazard ratio of 0.79 (p=0.003).

"The number needed to treat for 30 months (to save 1 primary end point) was 46," the authors report.

About 40% of the patients with diabetes were classified as very high risk, having had a prior cardiovascular event or stroke. In this subgroup, the advantage of amlodipine over hydrochlorothiazide was maintained, with event rates during follow-up of 13.6% versus 17.3% (HR 0.77, p=0.007). The number needed to treat was 28.

Early termination of the trial limited the ability to test fully for individual endpoints, the investigators note in their paper. However, they say, "There were some noteworthy findings for secondary end points."

One was significantly fewer acute coronary events (27% reduction) and coronary revascularizations (20% fewer) with amlodipine compared with hydrochlorothiazide among the diabetic cohort. Another was a lack of difference in heart failure rates, despite earlier suggestions that amlodipine monotherapy may not provide optimal heart failure protection.

"So, the take home message is that patients with diabetes or at high cardiovascular risk are best treated with a combination of a RAS blocker and amlodipine," Dr. Weber concluded. "This finding could affect drug selection in large numbers -- possibly in the millions -- of such patients in the United States and elsewhere."

The study was supported financially by Novartis.

http://content.onlinejacc.org/cgi/content/abstract/56/1/77

J Am Coll Cardiol 2010;56:77-85.

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