ASCOT at Odds With JNC Recommendations


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, due to a highly significant 14% relative risk reduction in all-cause mortality favoring the amlodipine/perindopril group.

Preliminary ASCOT results indicate that at the 5-year mark a total of 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 end points—all favoring 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% reduction 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.

ASCOT raises 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 treating hypertension. But the calcium channel blocker/ACE inhibitor combination was superior.

Dr. Sever is a consultant to Pfizer Inc. and the Servier Research Group, the study's major sponsors.

Recommended Reading

Simvastatin, Pravastatin May Lower Blood Pressure
MDedge Cardiology
Inhaled Iloprost Approved for Pulmonary Arterial Hypertension
MDedge Cardiology
Data Watch: Many Americans Don't Remember Results of BP, Cholestrol Tests
MDedge Cardiology
When Bosentan Treatment Fails, Sitaxsentan May Help
MDedge Cardiology