Meta分析提示他汀预防效果男女有别

《内科学文献》6月25日发表的一项Meta分析显示，他汀类药物用于女性二级预防某些心血管事件的效果较好，但预防卒中和全因死亡的效果并不优于安慰剂(Arch. Intern. Med. 2012;172:909-19)。

由于有临床研究在心血管疾病男性和女性患者中观察到的他汀类疗效不一致，因此纽约哥伦比亚大学神经学研究所的Jose Gutierrez博士及其同事希望通过Meta分析来弄清这一问题。该分析纳入符合以下标准的临床研究：采用随机化和双盲设计；对他汀类药物治疗与安慰剂进行比较而非与常规治疗或其他治疗进行比较；样本量至少为100例患者；随访时间至少为16周。最终共纳入11项研究，总样本量为43,191例患者。不过，仅20%的患者为女性。所研究的药物包括洛伐他汀、辛伐他汀、普伐他汀、氟伐他汀和阿托伐他汀。

在总研究人群中，他汀类药物能够有效预防任何心血管事件、全因死亡、冠状动脉死亡、任何心肌梗死(MI)、心脏介入治疗和任何类型卒中。根据性别对数据进行分层后发现，服用他汀类药物的男性患者的上述获益仍显著大于服用安慰剂的男性患者。服用他汀类药物的女性患者发生冠状动脉死亡、任何MI和需行冠状动脉介入治疗的风险显著低于服用安慰剂的女性患者，但前者的全因死亡和卒中风险并不显著低于后者。对随访时间最短者、年龄最大者或仅服用亲水性他汀类药物(相对亲脂性他汀类药物)者进行敏感性分析，仍观察到上述结果。

尚不清楚为什么男性与女性的治疗效果存在差异，一个原因可能是女性样本量小而不足以检出女性患者中的显著差异，研究者认为这是该Meta分析的主要局限性。其他原因可能在于这些研究所入选的女性患者的心血管风险较高，以及抗血小板药物的使用率较低。此外，性别之间的生物学差异，以及卫生保健和生物医学研究中的性别特异性差异可能也是原因所在。

该分析强调了他汀类药物的治疗效果存在性别差异。总体而言，分析结果支持在女性和男性中使用他汀类药物进行某些心血管事件的二级预防。

在随刊述评中，伦敦卫生与热带医学院的Fiona Taylor博士和Shah Ebrahim博士指出，该Meta分析的局限性不仅在于女性样本量较少，还在于纳入研究的标准较为严格。鉴于其他一些标准较宽松且纳入更多研究的Meta分析发现他汀类药物预防卒中和全因死亡的效果并无性别差异，因此Gutierrez等人可能排除了一些具有相关数据的研究。他们强调，不应当纠结于女性结果是否缺乏统计学意义，真正的议题在于女性中的效应大小是否与男性存在实质性差别。对不准确估计的效应的过度解读是Meta分析中的严重问题，Taylor博士和Ebrahim博士均认为，他汀类药物对女性的疗效如对男性的疗效一样，并无性别差异。

研究者、Taylor博士和Ebrahim博士均声明无经济利益冲突。

爱思唯尔  版权所有

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

Statins are beneficial in women for the secondary prevention of some cardiovascular events, but they don’t appear to be any better than placebo at preventing stroke or all-cause mortality, according to a meta-analysis reported in the June 25 issue of Archives of Internal Medicine.

These findings, from a study of 11 randomized, placebo-controlled clinical trials, underscore the differences between men and women in the benefits conferred by statin therapy, said Dr. Jose Gutierrez of the Neurological Institute, Columbia University, New York, and his associates.

Clinical trials have yielded conflicting results concerning the benefit of statins in women known to have cardiovascular disease, compared with those in men. Dr. Gutierrez and his colleagues hoped to clarify the question by restricting their meta-analysis to clinical trials that used randomization and double-blinding; compared statin therapy with placebo rather than usual care or other treatments; included samples of at least 100 subjects; and had follow-up of at least 16 weeks.

The 11 studies they reviewed had a pooled sample size of 43,191 subjects. Even so, only 20% of the subjects were women.

The drugs that were studied included lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin.

In the overall study population, statins were effective at preventing any cardiovascular event, all-cause mortality, coronary death, any myocardial infarction, cardiac intervention, and any type of stroke. When the data were stratified by sex, all of these benefits remained significant for men taking statins compared with men taking placebo.

However, women taking statins did not have significantly lower risk than women taking placebo for all-cause mortality or stroke. They did have significantly lower risk for coronary death, any MI, and coronary interventions, the investigators said (Arch. Intern. Med. 2012;172:909-19).

These results did not change in several sensitivity analyses, such as when the analysis was restricted to subjects with the shortest follow-up, the oldest subjects, or subjects taking only hydrophilic statins as opposed to lipophilic statins.

The reason for this discrepancy between men and women is uncertain. “One possibility is that the small sample size of women” – which they characterized as “a major limitation” of their meta-analysis – limited the power of the study to detect significant differences in women, the researchers noted.

“In addition, it is possible that the worse cardiovascular profile of women enrolled in studies, as well as the lower proportion of antiplatelet agent use, could account for some of these differences,” they wrote. Biological differences between the sexes likely play a role as well, as do sex-specific disparities in health care and in biomedical research, they added.

Overall, the study findings support the use of statins in women as in men for the secondary prevention of some cardiovascular events, Dr. Gutierrez and his associates said.

No conflicts of interest were reported.

Statins Work as Well in Women as in Men

In an invited commentary accompanying the report, Fiona Taylor, Ph.D., and Shah Ebrahim, D.M., wrote that “this meta-analysis is limited not just by the small proportion of women subjects acknowledged by the authors, but also by the strict inclusion criteria that studies had to meet to be used in the pooled analysis” (Arch. Intern. Med. 2012;172:919-20).

“It is likely that Gutierrez et al. excluded some studies with relevant data, since several other meta-analyses that had more inclusive criteria (and pooled many more than 11 studies) have reported that statins yield similar benefits in men and women for stroke and all-cause mortality,” said Dr. Taylor and Dr. Ebrahim, who are in the department of noncommunicable disease epidemiology and the Cochrane Heart Group at the London School of Hygiene and Tropical Medicine.

“Focusing on a lack of statistical significance in the findings for women is misleading. The real issue is not significance but whether the effect size in women is materially different from the effect size in men. Overinterpretation of imprecisely estimated effects is a serious problem in meta-analysis,” they noted.

“We suggest that statins work just as well in women as in men.”

Dr. Taylor and Dr. Ebrahim reported no financial conflicts of interest.