Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials.
BACKGROUND
Statin therapy in women without cardiovascular disease (CVD) is controversial, given the insufficient evidence of benefit. We analyzed sex-specific outcomes in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and synthesized the results with prior trials.


RESULTS
JUPITER participants included 6801 women > or =60 years of age and 11 001 men > or =50 years of age with high-sensitivity C-reactive protein > or =2 mg/L and low-density lipoprotein cholesterol <130 mg/dL randomized to rosuvastatin versus placebo. Meta-analysis studies were randomized placebo-controlled statin trials with predominantly or exclusively primary prevention in women and sex-specific outcomes (20 147 women; >276 CVD events; mean age, 63 to 69 years). Absolute CVD rates (per 100 person-years) in JUPITER women for rosuvastatin and placebo (0.57 and 1.04, respectively) were lower than for men (0.88 and 1.54, respectively), with similar relative risk reduction in women (hazard ratio, 0.54; 95% confidence interval, 0.37 to 0.80; P=0.002) and men (hazard ratio, 0.58; 95% confidence interval, 0.45 to 0.73; P<0.001). In women, there was significant reduction in revascularization/unstable angina and nonsignificant reductions in other components of the primary end point. Meta-analysis of 13 154 women (240 CVD events; 216 total deaths) from exclusively primary prevention trials found a significant reduction in primary CVD events with statins by a third (relative risk, 0.63; 95% confidence interval, 0.49 to 0.82; P<0.001; P for heterogeneity=0.56) with a smaller nonsignificant effect on total mortality (relative risk, 0.78; 95% confidence interval, 0.53 to 1.15; P=0.21; P for heterogeneity=0.20). Similar results were obtained for trials that were predominantly but not exclusively primary prevention.


CONCLUSIONS
JUPITER demonstrated that in primary prevention rosuvastatin reduced CVD events in women with a relative risk reduction similar to that in men, a finding supported by meta-analysis of primary prevention statin trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
Mora
Samia
S
Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. smora@partners.org
Glynn
Robert J
RJ
Hsia
Judith
J
MacFadyen
Jean G
JG
Genest
Jacques
J
Ridker
Paul M
PM
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D008078:Cholesterol, LDL / Q000097:blood*; D015897:Comorbidity; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D057239:Early Termination of Clinical Trials; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000517:prevention & control* / Q000601:surgery; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D012737:Sex Factors; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein