A pilot study with simvastatin and folic acid/vitamin B12 in preparation for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH).
OBJECTIVE
This study was conducted in preparation for the Study Evaluating Additional Reduction in Cholesterol and Homocysteine (SEARCH). SEARCH is a 12,000 patient 2X2 factorial study in post-myocardial infarction patients that will compare simvastatin 20 mg with simvastatin 80 mg to evaluate whether greater LDL-C reductions with simvastatin provide greater coronary event reductions. SEARCH will also test the hypothesis that lowering plasma homocysteine with folic acid and vitamin B12 will reduce coronary events. This pilot study was performed to determine whether any clinically meaningful interaction between simvastatin and folic acid/vitamin B12 exists.


RESULTS
Following a 2-week diet/placebo run-in period, 141 patients with primary hypercholesterolaemia were randomised to one of three treatments for 6 weeks: 80 mg/day simvastatin and 2 mg folic acid/0.8 mg vitamin B12 daily (combination group); or 80 mg/day simvastatin and placebo vitamins (simvastatin alone group); or 2 mg folic acid/0.8 mg vitamin B12 daily and placebo simvastatin (vitamins alone group). The combination group and simvastatin alone group experienced similar serum lipid changes with reductions in LDL-cholesterol of 55.2% and 51.5% respectively. The combination group and vitamins alone group experienced similar homocysteine lowering with reductions in homocysteine of 25.3% and 23.1% respectively. All therapies were well tolerated.


CONCLUSIONS
There was no detectable antagonistic effect when simvastatin and folic acid/vitamin B12 were administered concomitantly.
MacMahon
M
M
Chiltern International Ltd., Slough, UK.
Kirkpatrick
C
C
Cummings
C E
CE
Clayton
A
A
Robinson
P J
PJ
Tomiak
R H
RH
Liu
M
M
Kush
D
D
Tobert
J
J
D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005163:Factor Analysis, Statistical; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D010865:Pilot Projects; D010919:Placebos; D019821:Simvastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014805:Vitamin B 12 / Q000627:therapeutic use*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D014280:Triglycerides; D006710:Homocysteine; D005492:Folic Acid; D002784:Cholesterol; D019821:Simvastatin; D014805:Vitamin B 12