ORLANDO, FLA. — Combination antihypertensive therapy with a calcium channel blocker and angiotensin-converting enzyme inhibitor provides important clinical outcome advantages over the traditional β-blocker/diuretic combination, Peter S. Sever, Ph.D., said at the annual meeting of the American College of Cardiology.
He reported on 19,257 hypertensive patients free of coronary heart disease (CHD) who participated in the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure-Lowering Arm (ASCOT-BPLA) who were randomized to amlodipine/ perindopril or atenolol/ bendroflumethiazide. The study was halted early, after a mean 5.4 years, because of a highly significant 14% reduction in the relative risk of all-cause mortality that favored the group administered amlodipine/perindopril.
Preliminary ASCOT results indicate that at the 5-year mark, 1,178 cardiovascular events and procedures had occurred in the amlodipine/perindopril group, compared with 1,376 in the atenolol/bendroflumethiazide arm, said Dr. Sever, professor of clinical pharmacology and therapeutics at Imperial College, London.
Other significant differences in study end points—all of which favored the calcium channel blocker/ACE inhibitor combination—included:
▸ A 32% reduction in new-onset diabetes.
▸ A 23% decrease in the incidence of fatal and nonfatal stroke.
▸ A 24% drop in cardiovascular mortality.
▸ More favorable HDL and triglyceride levels.
Blood pressures were an average of 2.9/1.8 mm Hg lower in the amlodipine/perindopril group. But that's sufficient to account for only part of the observed benefit, according to Dr. Sever. Additional possible explanations include a suspected adverse interaction between atenolol/bendroflumethiazide and statin therapy, and more effective inhibition of the renin-angiotensin system by amlodipine/perindopril.
The ASCOT results raise serious questions about the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure VII guidelines recommending thiazide diuretics and β-blockers as initial treatment.
Discussant Richard Devereux, M.D., professor of medicine at Cornell University in New York, noted that the traditional β-blocker/diuretic combination was certainly not placebo therapy. These drugs are of long- established benefit in the treatment of hypertension. But the calcium channel blocker/ACE inhibitor combination was clearly superior.
Dr. Sever is a consultant to Pfizer Inc. and the Servier Research Group, the study's major sponsors.