Benefit of intensive statin therapy in women: results from PROVE IT-TIMI 22

Abstract

Background: Despite the known benefit of intensive statin therapy for reducing future cardiovascular events, its effectiveness in women has been questioned by some.

Methods and results: In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, 911 (21.9%) women and 3251 (78.1%) men were randomized to intensive statin (atorvastatin 80 mg) versus standard therapy (pravastatin 40 mg) therapy for a median duration of 2.1 years. The primary end point was death, myocardial infarction, unstable angina; revascularization (occurring after 30 days); or stroke. Safety end points included elevations in liver function tests, creatine kinase, and myalgias/myositis. Women had a reduction in low-density lipoprotein (LDL) of 42.8% from baseline at 30 days (to a median of 60 mg/dL) in the intensive therapy arm, with 88.8% reaching the LDL goal of <100 mg/dL and 65.0% of <70 mg/dL, compared with a 16.8% reduction in LDL (to a median of 88 mg/dL) in the standard therapy arm. Women receiving intensive statin therapy had a significant 25% relative reduction over standard dose (hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04) for the primary composite end point compared with a 14% reduction for men (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P=0.04; P-interaction, 0.38). No differences were observed between sexes for safety (all P-interaction ≥0.11).

Conclusions: This trial provides evidence that both women and men derived benefit from intensive statin therapy after acute coronary syndrome, and thus, sex should not be a factor in determining who should be treated with intensive statin therapy.

Trial registration: ClinicalTrials.gov NCT00382460.

Figure 1

Changes in LDL levels in women (A) and men (B) as stratified by randomization treatment group from baseline to 30-days, 4-, 8-, 16-months, and final visit. A greater percent reduction in LDL was observed in the high-dose atorvastatin group as compared to the standard-dose pravastatin group at all follow-up time points (all p<0.0001). Changes in hs-CRP levels in women (C) and men (D) as stratified by randomization treatment group from baseline to 30-days, 4-month, and final visit. The hs-CRP levels were significantly lower in the high-dose atorvastatin than standard-dose pravastatin arm at all follow-up time points (all p≤0.003).

Figure 2

Percentage of patients with (A) achieved LDL target levels of <100 mg/dL and <70 mg/dL and with (B) achieved hs-CRP <2 mg/L and/or LDL <70 mg/dL by randomized treatment group as stratified by gender at 30 days and at final visit. A. All p-values <0.001 when comparing proportion of patients with achieved target LDL levels with atorvastatin versus pravastatin as stratified by women and men. More proportion of men reached their target LDL levels with atorvastatin than women (all p-values <0.001). In patients on pravastatin, the proportion of men and women who achieved target LDL levels were not different (all p-values ≥0.13). B. All p-values ≤0.015 when comparing proportions of patients with achieved hs-CRP +/- LDL levels with treatment group as stratified by gender.

Figure 3

Kaplan Meier Curves of Primary Endpoint by study termination in women (A) and men (B).

Figure 4

Hazard ratios between intensive-dose Atorvastatin versus standard-dose Pravastatin therapy in women and men. All p-interactions were non-significant.

Figure 5

Hazard ratios of the primary endpoint in women subgroup treated with intensive lipid therapy (Atorvastatin 80) as compared to standard lipid lowering therapy (Pravastatin 40mg) therapy. ERT denotes estrogen replacement therapy. P-interaction=0.27 for menopausal status and lipid therapy; p-interaction=0.75 for ERT and lipid therapy.