The calcium channel blocker verapamil is no more effective than a diuretic or a beta-blocker in reducing risk for adverse cardiovascular events in patients with hypertension, according to an article in the April 23rd issue of The Journal of the American Medical Association.

Background information in the article states that patients diagnosed with hypertension in the U.S. are often given a calcium channel blocker to reduce risk for adverse events due to cardiovascular disease, but the benefit compared with that of other drug classes is controversial.

Henry R. Black, M.D., and his American colleagues conducted a study to determine the comparative efficacy of initial therapy with controlled-onset extended release verapamil versus that of atenolol (the representative beta-blocker) or hydrochlorothiazide (the representative diuretic) in preventing cardiovascular disease. The Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial was a double-blind, randomized clinical trial conducted at 661 centers in 15 countries.

A total of 16,602 participants diagnosed with hypertension who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998; follow-up ended on December 31, 2000. The trial included 8,179 participants who received verapamil 180 mg and 8,297 people who received either atenolol 50 mg or hydrochlorothiazide 12.5 mg. The primary endpoints were stroke, myocardial infarction, or cardiovascular-related death.

In the article, the authors stated that the study was closed 2 years earlier than planned (after an average follow-up of 3 years) by the sponsor, which cited “commercial reasons.” At that point, the results were unblinded.

"Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the controlled-onset extended release verapamil group and by 13.5 and 7.1 mm Hg for participants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the verapamil group versus 365 in atenolol or hydrochlorothiazide group," the authors wrote.

"The treatment regimens showed some minor and statistically nonsignificant differences in the incidence of each component of the primary end point. The incidence of acute [myocardial infarction] was about 18 percent lower with controlled-onset extended release verapamil than with the atenolol or hydrochlorothiazide group; this benefit was offset by a 15 percent higher risk of stroke."

The authors concluded, "In summary, CONVINCE was unable to demonstrate equivalence of a controlled-onset extended release verapamil-based antihypertensive regimen and a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, including the larger Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which found that the calcium channel blocker amlodipine was not superior to the diuretic chlorthalidone in reducing the rate of coronary heart disease or stroke and was associated with a higher rate of heart failure, these data indicate that the effectiveness of calcium channel blocker therapy in reducing cardiovascular disease-related morbidity and mortality is similar but not better than diuretic or beta-blocker treatment.

“These data support the recommendation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for low-dose diuretic (or possibly beta-blocker) therapy for hypertensive patients who have no specific indication for another antihypertensive drug."