Co-administration of ezetimibe and simvastatin in acute myocardial infarction

Recent trials in acute myocardial infarction indicate that intensive and early statin therapy that lowers low-density lipoprotein cholesterol (LDL-C) to < or = 70 mg dL(-1) is beneficial. The combination of statins with ezetimibe, a newly developed cholesterol-absorption inhibitor, can lead to a further reduction in LDL-C of up to 26%. In this study, we examined the rapidity and intensity of the lipid-lowering effect of ezetimibe co-administered with simvastatin immediately after myocardial infarction.

Sixty patients admitted for acute myocardial infarction were randomized to receive either simvastatin 40 mg (SIMVA), a combination of simvastatin 40 mg and ezetimibe 10 mg (EZE/SIMVA), or no lipid-lowering drugs (NLLD) and had their lipid levels assessed 2, 4 and 7 days later.

At baseline, cardiovascular risk factors were similar in all three groups [mean (SD) LDL-C of 141 (36) mg dL(-1)]. At days 2 , 4 and 7 there was no significant change in mean LDL-C levels in the NLLD group (-10%, -6%, and -9%, all P > 0.09), while there were significant reductions with SIMVA (-15%, -27%, and -25%, respectively, all P < 0.001 vs. day 0) and even greater reductions with co-administration of EZE/SIMVA (-27%, -41%, and -51%, respectively, all P < 0.001 vs. day 0). The percentages of patients achieving LDL-C below 70 mg dL(-1) at days 4 and 7 were substantially greater with EZE/SIMVA (45% and 55%, respectively) than with SIMVA (5% and 10%, respectively), while no NLLD patient reached this goal. Triglyceride levels showed a progressive increase in the NLLD group (+45% at day 7, P < 0.05 vs. day 0), no change in the SIMVA group, but a decrease in the EZE/SIMVA group (-17% at day 7, P < 0.05 vs. day 0). No significant difference in HDL-C levels, tolerability, or clinical events was observed between the three groups.

The co-administration of ezetimibe 10 mg with simvastatin 40 mg, by inhibiting cholesterol absorption and production, allowed more patients with acute myocardial infarction to reach LDL-C < or = 70 mg dL(-1) as early as the fourth day of treatment. The effects of such rapid and intense reduction in LDL-C on cardiovascular morbidity and mortality need to be evaluated in future clinical endpoint studies.