Effects of lovastatin and warfarin on early carotid atherosclerosis: sex-specific analyses. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.
BACKGROUND
Few clinical trials have documented the efficacy of preventive treatment in asymptomatic women.


RESULTS
Lovastatin and minidose warfarin were evaluated in a factorially designed, placebo-controlled, randomized trial. The primary outcome was 3-year change in the mean maximum intimal-medial thickness of the carotid arteries as measured by B-mode ultrasonography. Participants (n=919) were randomized to 1 of 4 treatment groups: lovastatin alone, warfarin alone, lovastatin+warfarin combination, or a double-placebo group. Eligible participants were asymptomatic for cardiovascular disease, with evidence of early carotid atherosclerosis and moderately elevated LDL cholesterol level. Almost half (n=445) of the participants were women. To avoid confounding, 117 women taking estrogen were excluded from analysis. Both sexes experienced reductions in disease progression with lovastatin; there was no evidence of an overall sex x treatment interaction (P=0.72). When estimates of the sex-specific results were examined post hoc, women experienced disease regression to the greatest extent with the lovastatin + warfarin combination (P=0.02), although the women on lovastatin alone also had a reduction in progression (P=0.09). Men experienced the greatest reduction with lovastatin alone (P=0.02), although there is a suggestion that warfarin may also reduce progression to some extent.


CONCLUSIONS
Lovastatin is beneficial in reducing disease progression in women and men. Warfarin has no effect in women, although it may reduce progression in men. In men, warfarin does not add to the benefit of lovastatin and has no advantage over lovastatin alone.
Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1063, USA. bbyingto@rc.phs.wfubmc.edu
R P
RP
Byington
G W
GW
Evans
M A
MA
Espeland
W B
WB
Applegate
D B
DB
Hunninghake
J
J
Probstfield
C D
CD
Furberg
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002340:Carotid Artery Diseases / Q000188:drug therapy*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging; D008078:Cholesterol, LDL / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D005163:Factor Analysis, Statistical; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D014463:Ultrasonography; D014859:Warfarin / Q000627:therapeutic use*
D008078:Cholesterol, LDL; D014859:Warfarin; D008148:Lovastatin