Aims: Endothelial dysfunction and plaque formation are features of atherosclerosis. Inhibition of L-type calcium channels or HMG-CoA pathway improves endothelial function and reduces plaque size. Thus, we investigated in stable coronary artery disease (CAD) the effects of a calcium antagonist on coronary endothelial function and plaque size.
Methods and results: In 454 patients undergoing PCI, acetylcholine (10(-6) to 10(-4) M) was infused in a coronary segment without significant CAD. Changes in coronary diameter were measured and an intravascular ultrasound examination (IVUS) was performed. On top of statin therapy, patients were randomized in a double-blind fashion to placebo or nifedipine GITS 30-60 mg/day and followed for 18-24 months. Blood pressure was lower on nifedipine than on placebo by 5.8/2.1 mmHg (P < 0.001) as was total and LDL cholesterol (4.8 mg/dL; P = 0.495), while HDL was higher (3.6 mg/dL; P = 0.026). In the most constricting segment, nifedipine reduced vasoconstriction to acetylcholine (14.0% vs. placebo 7.7%; P < 0.0088). The percentage change in plaque volume with nifedipine and placebo, respectively, was 1.0 and 1.9%, ns.
Conclusion: The ENCORE II trial demonstrates in a multi-centre setting that calcium channel blockade with nifedipine for up to 2 years improves coronary endothelial function on top of statin treatment, but did not show an effect of nifedipine on plaque volume.