Journal Article

From endothelial dysfunction to clinical events Concept and update on the ENCORE trials

L. Haegeli, K. Quitzau and T.F. Lüscher

in European Heart Journal Supplements

Published on behalf of European Society of Cardiology

Volume 3, issue suppl_B, pages B12-B19
Published in print May 2001 | ISSN: 1520-765X
Published online May 2001 | e-ISSN: 1554-2815 | DOI: http://dx.doi.org/10.1016/S1520-765X(01)90052-5
From endothelial dysfunction to clinical events Concept and update on the ENCORE trials

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In Western Countries morbidity and mortality are still mainly related to coronary artery disease and its complications, such as angina pectoris and myocardial infarction. An early event in atherosclerosis is endothelial dysfunction. For this reason, therapeutic interventions aiming to restore coronary endothelial dysfunction may be clinically relevant.

A number of studies have been performed in surrogate circulations, such as the human forearm, although not much is known about the effects of intervention in the coronary circulation. For the ENCORE I trial 343 patients with coronary artery disease undergoing percutaneous transluminal angioplasty, with or without stenting, have been randomized. After the coronary interventions, endothelial function was assessed by intracoronary (i.c.) infusion of increasing dosages of acetylcholine in a coronary segment without stenotic lesions. Quantitative coronary angiography (QCA) and Doppler flow velocity measurements were used to measure coronary responses to acetylcholine. Endothelium-independent responses are tested by i.c. adenosine and nitroglycerine. Patients were randomly assigned in a double-blind fashion to four treatment groups: placebo, nifedipine at 30–60 mg. day−1, cerivastatin at 400 μg . day−1 or their combination. Studies have been repeated in 247 patients after an interval of 6 months and the trial was completed in August 2000. This trial will determine whether or not endothelial function in patients with coronary artery disease is improved within 6 months by calcium antagonists and/or a statin alone or in combination.

The ENCORE II trial is scheduled to run for 2 years. It examines the correlation between endothelial function and structural atherosclerosis (as assessed by QCA and intravascular ultrasound [IVUS]) in 200 patients each treated with cerivastatin at a dose of 200 or 800 μg . day−1 compared with 200 patients treated with a combination of cerivastatin at a dose of 800 μg . day−1 and nifedipine at a dose of 30–60 mg . day−1. Endothelium-dependent responses of epicardial coronary arteries to acetylcholine at baseline as well as structural vascular changes, as assessed by IVUS, will be correlated and followed over 2 years. After 2 years the acetylcholine test, QCA and IVUS are to be repeated. Over 150 patients have so far been enrolled in the trial.

The ENCORE trials will show at the clinical level whether or not calcium antagonists and statins, alone or in combination, reverse early coronary endothelial dysfunction. In addition, these trials will address the question whether endothelial dysfunction and its pharmacological improvement are associated with progression or regression of atherosclerotic coronary artery disease. Finally, it may provide evidence whether this is reflected in fewer clinical events as suggested by several small observational studies.

Keywords: Coronary artery disease; atherosclerosis; endothelial dysfunction; nifedipine; cerivastatin

Journal Article.  0 words. 

Subjects: Cardiovascular Medicine

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