Background: Endothelial dysfunction is an important feature of atherosclerosis. Inhibition of the HMG-CoA pathway and of calcium channels improves endothelial function experimentally and in the forearm circulation. Thus, we investigated the effects of a statin and/or a calcium antagonist on coronary endothelial function in patients with coronary artery disease (CAD).
Methods and results: In 343 patients undergoing percutaneous coronary intervention in 29 centers, acetylcholine (10(-6) to 10(-4) mol/L) was infused in a coronary segment without angiographically significant CAD. Changes in coronary diameter were measured by quantitative angiography. Endothelium-independent responses were assessed by intracoronary adenosine (1.2 mg/mL) and nitroglycerin (250 microg). Thereafter, patients were randomized in a double-blind manner to placebo, cerivastatin 0.4 mg/d, nifedipine 30 to 60 mg/d, or their combination. Studies were repeated at 6 months. In the most constricted segment, nifedipine but not cerivastatin reduced vasoconstriction to acetylcholine (18.8% versus placebo 10.0%; P<0.05). Patients not taking ACE inhibitors showed a smaller improvement in the placebo group (6.0%), but nifedipine still had an effect (17.0%; P<0.05 versus placebo). Analysis of all evaluable coronary segments revealed an 11% reduction of acetylcholine-induced vasoconstriction in patients receiving nifedipine and cerivastatin (P<0.05 versus placebo). Cerivastatin lowered LDL cholesterol by 35% (P<0.001).
Conclusions: The ENCORE I trial demonstrates that multicenter studies on coronary endothelial function are feasible. After 6 months' treatment, nifedipine improved coronary endothelial function in the most constricted segment. The combination of nifedipine and cerivastatin tended to improve endothelial function; however, this only reached significance in an analysis of all coronary segments.