A pilot study with simvastatin and folic acid/vitamin B-12 in preparation for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)

Background and Aim: This study was conducted in preparation for the Study E valuating Additional Reduction in Cholesterol and Homocysteine (SEARCH). SE ARCH is a 12,000 patient 2x2 factorial study in post-myocardial infarction patients that will compare simvastatin 20 mg with simvastatin 80 mg to eval uate whether greater LDL-C reductions with simvastatin provide greater coro nary event reductions. SEARCH will also test the hypothesis that lowering p lasma homocysteine with folic acid and vitam B-12 will reduce coronary even ts. This pilot study was performed to determine whether any clinically mean ingful interaction between simvastatin and folic acid/vitamin B-12 exists. Methods and Results: Following a 2-week diet/placebo run-in period, 141 pat ients with primary hypercholesterolaemia were randomised to one of three tr eatments for 6 weeks: 80 mg/day simvastatin and 2 mg folic acid/0.8 mg vita min B12 daily (combination group); or 80 mg/day simvastatin and placebo vit amins (simvastatin alone group); or 2 mg folic acid/0.8 mg vitamin B-12 dai ly and placebo simvastatin (vitamins alone group). The combination group an d simvastatin alone group experienced similar serum lipid changes with redu ctions in LDL-cholesterol of 55.2% and 51.5% respectively. The combination group and vitamins alone group experienced similar homocysteine lowering wi th reductions in homocysteine of 25.3% and 23.1% respectively. All therapie s were well tolerated. Conclusions: There was no detectable antagonistic effect when simvastatin a nd folic acid/vitamin B-12 were administered concomitantly. Nutr Metab Card iovasc Dis (2000) 10:195-203 (C) 2000, Medikal Press.