Impact of gender in primary prevention of coronary heart disease with statin therapy: A meta-analysis

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Abstract

Background

Evidence of lipid-lowering from clinical trials that included women is adequate to support their use in secondary prevention in women with known coronary disease. However the role of statin therapy in primary prevention is still controversial, in particular for female gender. The aim of our study is to perform a meta-analysis comparing by gender the cardiovascular outcomes related to statin therapy in primary prevention.

Methods

We performed a meta-analysis including 8 randomized controlled trials (19,052 and 30,194 men, mean follow-up 3.9 years) that assessed the cardiovascular outcomes related to statin therapy, including studies that provided sex-specific results. MEDLINE and the Cochrane Database, were searched for articles published in English and other languages up to March 2008.

Results

Statins do not appear to have a beneficial effect on total mortality for both men and women in primary prevention over the 2.8- to 5.3 year study period (men: 95% Confidence Interval (CI) 0.83–1.04; comparison p = 0.22; women: 0.96; CI 0.81–1.13; p = 0.61). Statin therapy reduced the risk of coronary heart disease (CHD) events in men (0.59; CI 0.48–0.74; p = 0.0001), however in women this risk reduction was weakly significant (0.89 CI 0.79–1.00; p = 0.05) and disappeared when in sensitivity analysis, trials not entirely of primary prevention were excluded (HPS, PROSPER) (0.95 CI 0.78–1.16; comparison p = 0.562).

Conclusions

Our study showed that statin therapy reduced the risk of CHD events in men without prior cardiovascular disease, but not in women. Statins did not reduce the risk of total mortality both in men and women.

Introduction

The focus on cardiovascular risk treatment in women is rising. Indeed, for women the risk of cardiovascular events is lower than that of men at any given age and the onset of cardiovascular disease in women lags about 10 years behind men [1]. However, despite an overall reduction in the death rate due to cardiovascular disease in the United States over the last several decades, the rate of decline is less for women than men [2]. The impression that women are relatively protected from cardiovascular events, until the menopausal age, leads to a less aggressive approach to cardiovascular risk factors and, mostly, to a less intense cholesterol management than men. That could be one of the reasons of this gender difference on mortality for cardiovascular disease [3], [4].

Evidence of lipid-lowering from clinical trials that included women is adequate to support their use in secondary prevention in women with known coronary disease. However the role of lipid-lowering medications in primary prevention is still controversial, indeed, current evidence fails to report a clear reduction of total mortality or coronary heart disease events and mortality [5].

That may also depend on the insufficient number of women included in the trials as many did not include adequate numbers of women to allow sex-specific analyses. Previous systematic overviews did not report a comparison of anti-cholesterolemic effect of statin therapy in primary prevention between men and women. In addition, recently, a large trial of statin treatment in primary prevention (MEGA) [6], including more than 5000 women, showed that pravastatin in women with elevated cholesterol but no history of cardiovascular disease provides a benefit similar to that seen in men. Thus, performing a meta-analysis including also this study would yield additional insight into the issue. The aim of our study is to perform a meta-analysis comparing by gender the cardiovascular outcomes related to statin therapy in primary prevention.

Section snippets

Search strategy and data extraction

This meta-analysis is reported following the QUOROM statement [7]. Inclusion criteria for a study to be included in this overview were: randomized clinical trials of patients without known cardiovascular disease (primary prevention); available data on women and the effect of lipid-lowering drug therapy was assessed for at least 1 clinical outcome (total mortality, coronary heart disease (CHD) mortality, nonfatal myocardial infarction, CHD events, revascularization procedures). CHD events are

Results

Our original searches identified 1543 titles, after eliminating ineligible studies by review of titles and abstracts, we reviewed the full text of 135 articles. Of 12 [9], [10], [11], [12], [13], [14], [15], [16], [24], [25], [26], [27] identified studies that initially seemed to fit all inclusion criteria, ASPEN [24], CARDS [25] and two other studies were excluded [26], [27] as we did not obtain sex-specific data on outcomes, despite we contacted the principal investigators. Thus, we found 8

Discussion

Our study showed that statin therapy reduced the risk of CHD events in men without prior cardiovascular disease. However in women, the evidence of this protection is less clear. In men there was a great risk reduction (44%) that did not substantially change in sensitivity analysis, that is excluding trials not of primary prevention at all (HPS [13] and PROSPER [14]). In addiction, even excluding ALLHAT [11] (that was the only trial not reporting a significant risk reduction) from analysis, a

Acknowledgement

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [32].

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