Co-administration of ezetimibe and simvastatin in acute myocardial infarction

Authors


  • F. Chenot, P. F. Montant and O. S. Descamps have contributed equally to this work.

    Department of Internal Medicine (F. Chenot, P. F. Montant, O. Marcovitch, M. Blaimont, A. de Meester, O. S. Descamps); Centre for Medical Research, Centre Hospitalier Jolimont-Lobbes, Haine Saint-Paul, Belgium (O. S. Descamps).

Dr Olivier Descamps, Department of Internal Medicine, Centre Hospitalier Jolimont-Lobbes, Rue Ferrer 159, B-7100 Haine Saint-Paul, Belgium. Tel.: +32 64 23 42 15; fax: +32 64 23 38 42; e-mail: descaoli@skynet.be

Abstract

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.

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