This Article Full Text Full Text (PDF) All Versions of this Article: 107/3/422    most recent 01.CIR.0000046488.52939.BFv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation Related Collections Chronic ischemic heart disease Lipids Coronary imaging: angiography/ultrasound/Doppler/CC

(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

This article has been cited by other articles:

				H. Yasue, Y. Mizuno, E. Harada, T. Itoh, H. Nakagawa, M. Nakayama, H. Ogawa, S. Tayama, T. Honda, S. Hokimoto, et al. Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers. J. Am. Coll. Cardiol., May 6, 2008; 51(18): 1742 - 1748. [Abstract] [Full Text] [PDF]

				S. R. Freeman, A. L. Drake, L. F. Heilig, M. Graber, K. McNealy, L. M. Schilling, and R. P. Dellavalle Statins, Fibrates, and Melanoma Risk: a Systematic Review and Meta-analysis. J Natl Cancer Inst, November 1, 2006; 98(21): 1538 - 1546. [Abstract] [Full Text] [PDF]

				W.-W. Su, S.-T. Cheng, T.-S. Hsu, and W.-J. Ho Abnormal flow-mediated vasodilation in normal-tension glaucoma using a noninvasive determination for peripheral endothelial dysfunction. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3390 - 3394. [Abstract] [Full Text] [PDF]

				S. Fichtlscherer, C. Schmidt-Lucke, S. Bojunga, L. Rossig, C. Heeschen, S. Dimmeler, and A. M. Zeiher Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for 'pleiotropic' functions of statin therapy Eur. Heart J., May 2, 2006; 27(10): 1182 - 1190. [Abstract] [Full Text] [PDF]

				H.-K. Kuo, J. F. Bean, C.-J. Yen, and S. G. Leveille Linking C-Reactive Protein to Late-Life Disability in the National Health and Nutrition Examination Survey (NHANES) 1999-2002. J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2006; 61(4): 380 - 387. [Abstract] [Full Text] [PDF]

				M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita The clinical implications of endothelial dysfunction J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1149 - 1160. [Abstract] [Full Text] [PDF]

				P. D. Thompson, P. Clarkson, and R. H. Karas Statin-Associated Myopathy JAMA, April 2, 2003; 289(13): 1681 - 1690. [Abstract] [Full Text] [PDF]