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

Abstract

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.

Methods and 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.

Figure 1

Effects of rosuvastatin on the primary composite endpoint according to baseline characteristics. The dashed overall line indicates the overall hazard ratio for the entire cohort (men and women combined).

Figure 1

Effects of rosuvastatin on the primary composite endpoint according to baseline characteristics. The dashed overall line indicates the overall hazard ratio for the entire cohort (men and women combined).

Figure 2

Relative risk of allocation to statin compared with placebo in women in relation to CVD in exclusively primary prevention trials (panel A) and predominantly or exclusively primary prevention trials (panel B). Similarly for total mortality (panels C and D). The size of the squares is proportional to the number of events. Mean age, % diabetic, and statin dose were, respectively, as follows: AFCAPS/TexCAPS 63 years, 3%, lovastatin 20–40 mg/day; ALLHAT-LLA 66 years, 35%, pravastatin 20–40 mg/day; ASCOT-LLA 63 years, 24%, atorvastatin 10 mg/day; MEGA 60 years, 18%, pravastatin 10–20 mg/day; JUPITER 69 years, 0%, rosuvastatin 20 mg/day.

Figure 2

Relative risk of allocation to statin compared with placebo in women in relation to CVD in exclusively primary prevention trials (panel A) and predominantly or exclusively primary prevention trials (panel B). Similarly for total mortality (panels C and D). The size of the squares is proportional to the number of events. Mean age, % diabetic, and statin dose were, respectively, as follows: AFCAPS/TexCAPS 63 years, 3%, lovastatin 20–40 mg/day; ALLHAT-LLA 66 years, 35%, pravastatin 20–40 mg/day; ASCOT-LLA 63 years, 24%, atorvastatin 10 mg/day; MEGA 60 years, 18%, pravastatin 10–20 mg/day; JUPITER 69 years, 0%, rosuvastatin 20 mg/day.

Figure 2

Relative risk of allocation to statin compared with placebo in women in relation to CVD in exclusively primary prevention trials (panel A) and predominantly or exclusively primary prevention trials (panel B). Similarly for total mortality (panels C and D). The size of the squares is proportional to the number of events. Mean age, % diabetic, and statin dose were, respectively, as follows: AFCAPS/TexCAPS 63 years, 3%, lovastatin 20–40 mg/day; ALLHAT-LLA 66 years, 35%, pravastatin 20–40 mg/day; ASCOT-LLA 63 years, 24%, atorvastatin 10 mg/day; MEGA 60 years, 18%, pravastatin 10–20 mg/day; JUPITER 69 years, 0%, rosuvastatin 20 mg/day.

Figure 2

Relative risk of allocation to statin compared with placebo in women in relation to CVD in exclusively primary prevention trials (panel A) and predominantly or exclusively primary prevention trials (panel B). Similarly for total mortality (panels C and D). The size of the squares is proportional to the number of events. Mean age, % diabetic, and statin dose were, respectively, as follows: AFCAPS/TexCAPS 63 years, 3%, lovastatin 20–40 mg/day; ALLHAT-LLA 66 years, 35%, pravastatin 20–40 mg/day; ASCOT-LLA 63 years, 24%, atorvastatin 10 mg/day; MEGA 60 years, 18%, pravastatin 10–20 mg/day; JUPITER 69 years, 0%, rosuvastatin 20 mg/day.