Data from the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study indicate that amlodipine decreases risk of cardiovascular events and related deaths in patients with coronary artery disease and normal blood pressure, according to an article in the November 10th issue of the Journal of the American Medical Association. Investigators found that the angiotensin-converting enzyme inhibitor enalapril had similar effects, but to a lesser extent.

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

In the CAMELOT study, Steven E. Nissen, MD, and colleagues examined the effects of antihypertensive drugs in 1,991 patients with coronary artery disease and normal blood pressure through 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 examinations to determine if either or both medications reduced progression of atherosclerosis.

The primary end point was the time to first occurrence of an adverse cardiovascular event such as cardiovascular death, nonfatal myocardial infarction, 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 mmHg, amlodipine reduced blood pressure an average of 5/3 mmHg and compared with 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, that is, 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 wrote.

“Enalapril treatment also reduced blood pressure by an average of 5/2 mmHg. 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 ultrasound 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 coronary artery disease and a ‘normal’ blood pressure,” the researchers wrote. “These results suggest that the optimal blood pressure range for patients with coronary artery disease may be substantially lower than indicated by current guidelines.”

In an accompanying editorial, Carl J. Pepine, MD, wrote that findings from the current study raise the question of the optimal target systolic blood pressure to prevent progression of coronary atherosclerosis.

“There are very limited outcome data among patients with coronary artery disease in whom blood pressure has been lowered to the levels reported in the current study. Accordingly, the optimal blood pressure level in the patient with coronary disease is unclear. The data from [another study] and CAMELOT would suggest that the optimal level is clearly lower than 140 mmHg systolic and perhaps in the 120 mmHg range. The benefits (and risks) of various blood pressure levels within the so-called normal range and different blood pressure lowering strategies will require more randomized trial data. But the CAMELOT findings provide direction for future trials with patients randomized to various strata of blood pressure targets below 140 mmHg systolic.”