Calcium channel blocker reduces adverse cardiovascular events

The calcium channel blocker amlodipine decreases the risk of cardiovascular events (such as heart attack or heart-disease related deaths) in patients with coronary artery disease and normal blood pressure, as does the ACE inhibitor enalapril, but to a lesser extent, according to a study in the November 10 issue of JAMA.

Despite more than 30 years of clinical trials, uncertainty has existed regarding the optimal use of antihypertensive drugs in patients with coronary artery disease (CAD), according to background information in the article.

Steven E. Nissen, M.D., of the Cleveland Clinic Lerner School of Medicine, Cleveland, and colleagues examined the effects of antihypertensive drugs in 1,991 patients with CAD and normal blood pressure in the Comparison of Amlodipine vs. Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study, a double-blind, randomized, multicenter 24-month trial (enrollment April 1999-April 2002). Patients received either the calcium channel blocker amlodipine (10 mg); the angiotensin-converting enzyme (ACE) inhibitor enalapril (20 mg); or placebo. In addition, a subset of 274 patients underwent serial intravascular ultrasound (IVUS) examinations to determine if either or both medications reduced the progression of atherosclerosis.

The primary end point was the time to first occurrence of an adverse cardiovascular event such as cardiovascular death, nonfatal heart attack, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke, or diagnosis of vascular disease.

The researchers found that for patients with a baseline systolic blood pressure averaging only 129/78 mm Hg, amlodipine reduced blood pressure an average of 5/3 mm Hg and compared to placebo, produced a 31 percent relative reduction (6.5 percent absolute reduction; 23.1 percent event-rate for placebo, 16.6 percent event rate for amlodipine) in cardiovascular events. “The number needed to treat for amlodipine is 16, i.e., for every 16 patients who receive amlodipine, there will be on average 1 adverse cardiovascular event avoided during the 2-year period compared with patients who receive placebo,” the authors write. “Enalapril treatment also reduced blood pressure by an average of 5/2 mm Hg. However, the observed 15.3 percent relative reduction compared to placebo (2.9 percent absolute reduction; 20.2 percent event rate in the enalapril group) in cardiovascular events was not statistically significant.”

The IVUS substudy showed evidence of slowing of progression of coronary artery atherosclerosis with amlodipine.

“… the current study provides important new findings regarding the administration of antihypertensive agents to patients with CAD and a ‘normal’ blood pressure,” the researchers write. “These results suggest that the optimal blood pressure range for patients with CAD may be substantially lower than indicated by current guidelines.”