Published online before print January 20, 2003, doi: 10.1161/01.CIR.0000046488.52939.BF
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(Circulation. 2003;107:422.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Effect of Nifedipine and Cerivastatin on Coronary Endothelial Function in Patients With Coronary Artery Disease
The ENCORE I Study (Evaluation of Nifedipine and Cerivastatin On Recovery of coronary Endothelial function)
, The ENCORE Investigators**The ENCORE Investigators are listed in the Appendix.
Correspondence to Thomas F. Lüscher, MD, FRCP, FACC, Professor and Head of Cardiology, University Hospital, CH-8091 Zürich, Switzerland. E-mail cardiotfl{at}gmx.ch
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 µg). 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.
Key Words: coronary disease • endothelium • acetylcholine • angiography • drugs
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