Long-term effect of nifedipine on vasomotion and vessel morphology in patients with coronary artery disease: an intravascular ultrasound-assisted evaluation - ENCORE II

Description:

The goal of the trial was to evaluate the long-term effect of the calcium antagonist nifedipine plus statin therapy on coronary endothelial function compared with statin therapy alone in patients with coronary heart disease.

Hypothesis:

Treatment with nifedipine plus statin therapy will be associated with improved endothelial function compared with statin therapy alone at 18-24 month follow-up.

Study Design

Study Design:

Patients Enrolled: 226
Mean Follow Up: 18-24 months
Mean Patient Age: Mean age 58.3 years
Female: 18

Patient Populations:

Coronary artery disease verified by angiography, ejection fraction >40%, left coronary artery branch with <40% stenosis, and at least one segment with no vasodilation on acetylcholine

Exclusions:

Myocardial infarction within two weeks, unstable angina, or recent syncope

Primary Endpoints:

Change in minimum lumen diameter in response to acetylcholine at 18-24 month follow-up

Secondary Endpoints:

Atheroma volume by IVUS at 18-24 months

Drug/Procedures Used:

For the initial trial design, patients were randomized to cerivastatin (0.2 mg), cerivastatin (0.8 mg), or nifedipine (30-60 mg) plus cerivastatin (0.8 mg). During the trial, cerivastatin was withdrawn from the market. The design was modified to allow lipid-lowering therapy per the current guidelines instead of a specific statin. Patients underwent baseline and follow-up (18-24 months) quantitative coronary angiography and intravascular ultrasound (IVUS). Overall sample size was 114 patients in the nifedipine group and 112 patients in the control group.

Principal Findings:

The primary endpoint of percent change in minimum lumen diameter in response to acetylcholine was greater in the nifedipine arm than the control group (18.3% vs. 6.9%, p=0.0007). In the subset of patients enrolled after cerivastatin use was discontinued, the difference in the primary endpoint was larger (17.5% for nifedipine vs. 0.95% for control, p<0.0001). There was no difference in the secondary endpoint of atheroma volume on IVUS by treatment group in all patients (3.2% progression for nifedipine vs. 5.4% for control, p=0.594) or in patients enrolled after cerivastatin use was discontinued (3.3% progression for nifedipine vs. 11.2% for control, p=0.162). There was also no difference in the absolute change in atheroma volume (-2.1 vs. 3.0 mm3, p=NS).

Interpretation:

Among patients with coronary heart disease, treatment with nifedipine plus statin therapy was associated with an improvement in the primary endpoint of coronary endothelium function at 18-24 months compared with statin therapy alone, but was not associated with plaque size on IVUS. These data confirm the results in ENCORE I, which also showed an improvement in endothelial function associated with nifedipine plus statin therapy. These findings may explain in part the reduction in angiography and interventions during long-term follow-up in the nifedipine arm of the recently reported ACTION trial.

References:

L├╝scher TF. ENCORE II: the long-term effect of nifedipine on vasomotion and vessel morphology in patients with coronary artery disease: an intravascular ultrasound-assisted evaluation. Paper presented at the European Society of Cardiology Congress 2004, 29 August-1 September, Munich, Germany.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Coronary Artery Disease, Endothelium, Plaque, Atherosclerotic, Coronary Angiography, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pyridines, Constriction, Pathologic, Nifedipine, Calcium Channel Blockers


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