Published Online
on January 20, 2003

A more recent version of this article appeared on January 28, 2003

This Article 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 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 Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL Medline Plus Health Information Coronary Artery Disease Statins Related Collections Lipids Coronary imaging: angiography/ultrasound/Doppler/CC Chronic ischemic heart disease

Submitted on July 23, 2002
Revised on October 7, 2002
Accepted on October 9, 2002

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 ^*

^* To whom correspondence should be addressed. 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:

				T. F. Luscher, M. Pieper, M. Tendera, M. Vrolix, W. Rutsch, F. van den Branden, R. Gil, K.-O. Bischoff, M. Haude, D. Fischer, et al. A randomized placebo-controlled study on the effect of nifedipine on coronary endothelial function and plaque formation in patients with coronary artery disease: the ENCORE II study Eur. Heart J., July 1, 2009; 30(13): 1590 - 1597. [Abstract] [Full Text] [PDF]

				P. Ganz, J. E. Ho, and P. Y. Hsue Structural and functional manifestations of human atherosclerosis: do they run in parallel? Eur. Heart J., July 1, 2009; 30(13): 1556 - 1558. [Full Text] [PDF]

				A Yilmaz, H Mahrholdt, A Athanasiadis, H Vogelsberg, G Meinhardt, M Voehringer, E-M Kispert, C Deluigi, H Baccouche, E Spodarev, et al. Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis Heart, November 1, 2008; 94(11): 1456 - 1463. [Abstract] [Full Text] [PDF]

				T. Sugiura, T. Kondo, Y. Kureishi-Bando, Y. Numaguchi, O. Yoshida, Y. Dohi, G. Kimura, R. Ueda, T. J. Rabelink, and T. Murohara Nifedipine Improves Endothelial Function: Role of Endothelial Progenitor Cells Hypertension, September 1, 2008; 52(3): 491 - 498. [Abstract] [Full Text] [PDF]

				P. Ong, A. Athanasiadis, S. Hill, H. Vogelsberg, M. Voehringer, and U. Sechtem Coronary Artery Spasm as a Frequent Cause of Acute Coronary Syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study J. Am. Coll. Cardiol., August 12, 2008; 52(7): 523 - 527. [Abstract] [Full Text] [PDF]

				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]