CAMELOT: Normotensives with CAD benefit from BP lowering

NEW ORLEANS — Patients with coronary artery disease and normal blood pressure had a reduced risk of adverse cardiac events when given blood pressure-lowering agents in the CAMELOT trial.

Results of CAMELOT (The Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis) suggest advantages for the calcium antagonist amlodipine (Norvasc, Pfizer) compared to the ACE inhibitor enalapril (Vasotec, Merck).

Recent trials have indicated that both calcium channel antagonists and ACE inhibitors offer benefits to normotensive patients with CAD, but few studies have specifically targeted patients with angiographically documented CAD, said Bertram Pitt, MD, University of Michigan. Studies have also restricted enrollment to those with normal blood pressure.

CAMELOT, a double-blind randomized trial, enrolled 1,997 patients at 100 North American and European sites. Patients were randomized for two years to amlodipine (10 mg), enalapril (20 mg) or placebo. The primary endpoint of the study was the incidence of cardiovascular events for amlodipine compared to placebo, and for enalapril compared to placebo.

Events included cardiovascular death, nonfatal MI, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, stroke or transient ischemic attack and new diagnosis of peripheral vascular disease.

Patients assigned amlodipine had a 31% reduction in cardiovascular events after a two-year period. Patients assigned enalapril experienced a less significant 15% reduction in cardiovascular events after the same period.

Primary endpoint analysis showed a significant reduction in cardiovascular events for amlodipine vs. placebo (110 vs. 151, P=.003), Pitt said in an interview at the American Heart Association 2004 Scientific Sessions. The difference for enalapril (136) vs. placebo was not significant.

Blood pressure was reduced significantly (P<.001) by both amlodipine and enalapril vs. placebo: -4.8/2.5 mm Hg amlodipine, -4.9/2.4 mm Hg enalapril, and +0.7/0.6 mm Hg placebo). Baseline blood pressure averaged 129/78 mm Hg for all patients.

Pitt said that patients given amlodipine had fewer angina hospitalizations and fewer revascularizations than the other patients. “What this says to me is that amlodipine is really a pretty good antianginal agent,” he said. The stopping of atherosclerosis progression by amlodipine seems to be related to blood pressure reductions, even in these normotensive subjects, he said.

“There are good data that hypertension is a stimulus toward atherosclerosis. What we have called normal — less than 140 mm Hg or even less than 130 mm Hg — may not be optimal. Optimal may be down to less than 120 mm Hg,” Pitt said. He cautioned about extrapolating too far, adding that a large, long-duration trial would be needed for a definitive conclusion.

Regarding the divergent mechanisms of amlodipine and enalapril, Pitt said that the calcium antagonist with its effects on smooth muscle cells offers short-term benefits in endothelial function, reducing anginal symptoms, while the ACE inhibitor offers longer-term preventive effects on plaque rupture.

“CAMELOT suggests that we should be using amlodipine for people with coronary artery disease, I think, to reduce revascularizations. It does not tell us, necessarily, that in the long run it is better than ACE inhibitors,” he said. – by Walter Alexander

For more information:

• Nissen, SE. The comparison of amlodipine versus enalapril to limit occurrences of thrombosis. JAMA 2004; Nov. 10, 2004.(292: 2217-2226).