Study PROVEs IT--Intensive statin therapy beneficial for both men and women

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Results of a subgroup analysis of the PROVE IT-TIMI 22 trial showed that despite the fact that the effectiveness of statins in women has been questioned, both sexes benefit from intensive statin therapy after acute coronary syndrome (ACS), according to the study’s results published online April 12 in Circulation: Cardiovascular Quality and Outcomes.

“Although the effects of statins on reducing future cardiovascular events are well established in men, the generalizability to women are less certain because of the relatively few number of women included in these large, randomized secondary prevention trials ( <20% in each trial),” the authors wrote.

Quynh A. Truong, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues set out to better understand the benefits of intensive statin therapy for reducing future cardiovascular (CV) events in both sexes to see whether women faired worse with statin treatment.

During the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22) trial, Truong et al enrolled 911 women and 3,251 men and randomized them to receive an intensive 80 mg dose of atorvastatin (465 patients) or standard therapy, a 40 mg dose of pravastatin (446 patients), for a median of 2.1 years. The primary endpoint of the study was death, MI, unstable angina, revascularization occurring after 30 days or stroke.

Women were on average 2.6 years older and were more likely to have diabetes, hypertension and a history of HF; however, men were more likely to be smokers, and have a history of MI and CABG. There was no difference in the percentage of prior statin use between women and men, 26.3 percent vs. 24.9 percent.

LDL levels were similar in both sexes—106 mg/dL—but, HDL levels were higher in women compared with men, 44 mg/dL vs. 37 mg/dL.

At 30 days, the researchers reported that LDL levels in women were reduced by 42.8 percent to 60 mg/dL in the atorvastatin (Lipitor, Pfizer) arm compared with a 16.8 percent reduction in the pravastatin (Pravachol/Selektine, Bristol-Myers Squibb/Sankyo Pharma) arm. Men had a reduction of 47.5 percent at 30 days in the atorvastatin arm compared with an 18.1 percent reduction in the pravastatin arm.

While the reduction in LDL was greater in men than in women in the atorvastatin group, LDL reductions in the pravastatin arm were not statistically significant between sexes. Additionally, the researchers noted that at 30 days, 88.8 percent of women in the atorvastatin reached target LDL levels of less than 100 mg/dL compared to 67.5 percent in the pravastatin arm. These same levels for men were 95.5 percent and 66.1 percent, respectively.

The researchers noted that increases in HDL levels at 30 days were higher in the pravastatin group compared with the atorvastatin group in both sexes. Women saw a 5.3 percent increase in HDL levels with pravastatin and a 0 percent increase with atorvastatin while men saw a 2.9 percent increase with pravastatin versus 0 percent with atorvastatin.

As for the primary endpoint, women who received atorvastatin saw a 25 percent relative reduction compared with men who had only a 14 percent relative reduction. The absolute reductions were 6.7 percent for women administered atorvastatin and 3.2 percent for men.

“In this subgroup analysis of PROVE IT-TIMI 22, use of intensive statin therapy with high-dose atorvastatin after ACS led to a significant reduction in cardiovascular events in women (as well as in men) and with similar safety profiles compared to standard-dose pravastatin,” the authors wrote.

The researchers found that for a 1 percent reduction in events, mean reductions in LDL levels needed in women were 1 mg/dL, but the same benefit in men was reached with a reduction of 2.4 mg/dL.

“The clinical impact of intensive statin therapy is quite robust in women and reinforces the value of treating women with intensive statin therapy after ACS to reduce cardiovascular events,” the authors wrote. However, the benefit of statin therapy for women remains controversial and some say that data are “insufficient."

The authors continued, “Despite having less significant LDL lowering with intensive compared to standard lipid-lowering therapy than men, women had dramatic and significant reductions in clinical events...Both women and men benefit from high-dose statin therapy after ACS, and they should be treated with intensive regimens.”

The trial was funded