A recent meta-analysis(content.onlinejacc.org) designed to evaluate the effect of statins in reducing cardiovascular events in both men and women determined that statin therapy was associated with statistically significant decreases in these events, as well as in all-cause mortality, in both genders. But these findings may be too vague to be useful in clinical practice, according to Lee Green, M.D., professor of family medicine at the University of Michigan, Ann Arbor.
Previously, women have not participated in primary prevention trials to the extent that men have, leaving some doubt about the effectiveness of statins for primary prevention in women. The study authors acknowledge this gap, noting that although previous "reviews and meta-analyses have shown improved outcomes with statins in both men and women without significant interaction by sex … they did not show statistically significant effects in women."
However, said Green, who also is a past member of the (then) AAFP Commission on Clinical Policies and the AAFP Commission on Continuing Professional Development, the methodology of the current meta-analysis exhibits the same problematic issues other studies on this topic have shown.
"The studies on which it's based that are asserted to be primary prevention include significant numbers of patients who (reported previous cardiovascular disease [CVD])," he said.
Researchers analyzed 18 clinical trials involving statins that included gender-specific outcomes. All trials were controlled, randomized and double-blinded. Of the 18 trials, eight were classified as primary prevention and 10 as secondary prevention.
- A recent meta-analysis concludes that statin therapy decreases cardiovascular events and all-cause mortality in both men and women.
- Because women have not participated as frequently as men in many primary prevention trials involving statins, some doubt has existed as to whether these medications were effective as primary prevention for them.
- This study reports that the benefit of statins in reducing primary endpoints, as defined in the original trials assessed, was seen in men and women and in both primary and secondary prevention with no significant difference between genders.
- One FP expert, however, questions some of the researchers' conclusions because a number of the so-called primary prevention trials analyzed included participants who may have had existing cardiovascular disease.
Rates of occurrence of primary endpoint (as defined in each original study) and all-cause mortality (where available) for intervention and control groups were calculated for each study as a whole, as well as by gender. Overall pooled treatment effects also were calculated for each study as a whole and by gender. In addition, separate analyses were performed for primary and secondary prevention trials by level of baseline risk and type of endpoint.
It's worth noting that five of the eight "primary prevention" studies included between 14 percent and 87 percent of patients who might have had CVD, leaving only three studies composed exclusively of patients with no previous CVD. This discrepancy was addressed in the study's sensitivity analysis, but not in the overall analysis.
Of the three studies involving patients with no prior CVD, one was composed of 15 percent women, one of 38 percent women and the third of 69 percent women. The study that included the highest percentage of women demonstrated the lowest drop in LDL levels.
"Primary prevention benefit is clear for middle-aged males at elevated risk," Green told AAFP News Now. "That group has a high base rate, and much of their risk is attributable to lipids. For women, the base rate is much lower, and for elders -- much of their risk is related to age, not lipids."
In an editorial that accompanied the meta-analysis, Lori Mosca, M.D., of Columbia University in New York, addressed the same issue, pointing out that the focus of the meta-analysis was on relative risk reduction, and there was limited assessment of risk or costs of therapy. Furthermore, she noted, a recent Cochrane review has suggested that a patient's annual mortality risk should drive decisions about the use of statins in primary prevention.
Given that women without CVD have a lower annual mortality risk and a lower CVD risk than do men without CVD, "the absolute benefit of statins will typically be less for women than men, suggesting it might be appropriate that women receive statins less frequently than men in the setting of primary prevention," she said.
"The current meta-analysis provides information about sex-specific relative risk benefit and not absolute benefit. Both the absolute risk of CVD and the proportionate risk reduction associated with statin therapy are needed to make informed clinical choices with regard to the use of statins for primary prevention."
"It's clear that both women and men benefit in secondary prevention," Green affirmed. "The problem is primary prevention, and this replowing of old ground does not really change anything."
More From AAFP
American Family Physician: "Considerations for Safe Use of Statins: Liver Enzyme Abnormalities and Muscle Toxicity"
(March 15, 2011)
American Family Physician: AFP by Topic: "Coronary Artery Disease/Coronary Heart Disease" (Some content available to members/paid subscribers only)
Cardiovascular Risk Reduction Learning Community in DARTNet