Objectives: To assess the efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia and coronary artery disease (CAD).
Design and setting: Prospective, multicentre, randomized, double-blind, placebo-controlled trial conducted in three Middle Eastern countries.
Patients: Patients with known CAD, who were being treated with simvastatin 20 mg and had low-density lipoprotein cholesterol (LDL-C) concentrations of 2.6 to 4.1 mmol/l, were randomized to receive daily coadministration of ezetimibe 10 mg or placebo.
Main outcome measures: The primary outcome was percentage reduction of LDL-C after 6 weeks of randomization. Secondary endpoints included number of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C level and safety and tolerability.
Results: We enrolled 144 patients of whom 120 had blood available for final analysis. The coadministration of ezetimibe with ongoing simvastatin therapy resulted in a statistically significant additional reduction in LDL-C concentration as compared with simvastatin monotherapy (-26.7 versus -9.1%, respectively; total additional reduction of 17.6%, P < 0.0001). More patients in the ezetimibe and simvastatin group achieved NCEP ATP III LDL-C target levels than in the simvastatin monotherapy group (70 versus 33%, respectively; P = 0.0001). The coadministration of ezetimibe with simvastatin was well tolerated with a safety profile similar to that of simvastatin monotherapy.
Conclusion: When coadministered with simvastatin therapy, ezetimibe resulted in significant additional reduction in LDL-C and enabled more patients to achieve NCEP ATP III LDL-C target levels. This was achieved safely and with excellent tolerability.