Background Recent trials in acute myocardial infarction indicate that intensive and early statin therapy that lowers low-density lipoprotein cholesterol (LDL-C) to ≤ 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.
Materials and methods 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.
Results 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.
Conclusions 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 ≤ 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.