January 30, 2012 (Boston, Massachusetts)— A large meta-analysis has shown that statins are as effective in women as in men for the reduction of cardiovascular outcomes and all-cause mortality, leaving investigators to conclude that statins should be used in all appropriate patients regardless of sex .
"There have been a large number of clinical trials looking at the benefits of statin use, but the ability for us to prove that the benefits extend to both men and women has been limited, in part because of numbers," lead investigator Dr William Kostis (Massachusetts General Hospital, Boston) told heartwire .
"There have been studies that have shown benefits in men, and where they have shown a trend toward benefit in women they were unable to show a statistically significant difference. Because of this, we undertook the meta-analysis, and what we found was what we had hoped to find, and that was that the benefits of reducing cardiovascular outcomes and all-cause mortality extend to both men and women."
The meta-analysis, published in the February 7, 2012 issue of the Journal of the American College of Cardiology, included 18 clinical trials of statin therapy with clinical outcomes for men and women. The analysis included 141 235 subjects, including 40 275 women, from studies such as JUPITER, ALLHAT-LLT, ASCOT-LLA, Heart Protection Study, MEGA, PROVE-IT, and TNT, among others. Ten of the studies were secondary-prevention studies, and eight studies were designed as primary-prevention trials, although five of the primary-prevention studies did include a proportion of patients with cardiovascular disease.
In an editorial accompanying the study , Dr Lori Mosca (Columbia University Medical Center, New York) states that the finding of "no interaction by sex in this contemporary meta-analysis is concordant with prior meta-analyses that were limited by smaller numbers of women and suggests statin therapy has similar proportional benefits for men and women, regardless of the type of end point studied or the level of population risk."
Primary- and Secondary-Prevention Studies
In the meta-analysis, statin therapy significantly reduced the risk of cardiovascular events 19% in women and 23% in men. The treatment effect in women was more pronounced in the secondary-prevention studies, where a 22% reduction in the risk of cardiovascular events was observed, compared with the 15% reduction in outcomes found in the primary-prevention studies. The reduction in events was similar in studies that used placebo/usual care and low-dose statin therapy as the control arm.
Regarding all-cause mortality, the researchers report that treatment with statin therapy significantly reduced the risk of death in women by 10% in the primary- and secondary-prevention studies and by 13% when the primary-prevention studies were analyzed separately. The effect of statin therapy on all-cause mortality in women enrolled in the secondary-prevention studies was not statistically significant, and there was only a trend toward a reduction in all-cause mortality in men enrolled in the primary-prevention studies.
When investigators stratified patients by expected mortality, they found that statin therapy resulted in a significant reduction in cardiovascular outcomes in patients at low, medium, and high risk.
"This is a very large meta-analysis and it gives us good evidence to show that the benefit of statin use extends to both men and women," said Kostis. "It even extends to people considered low risk. I think going forward, as there will continue to be other statin trials and new agents, we want to make sure that women and people from all demographics are represented in the population studies, because it will allow us to show that benefits extend to all subpopulations, and if there are differences to see what they are with regard to safety and efficacy."
The Institute of Medicine has recently called for more sex-specific reporting of data for safety and efficacy outcomes. In the meta-analysis by Kostis and colleagues, there were not enough data to evaluate the adverse side effects of statin therapy in women, as just two studies reported sex-specific adverse-outcomes data. Future sex-specific results in cardiovascular medicine trials are needed to assess absolute and relative benefits, adverse outcomes, and cost-effectiveness.
Good for the Goose . . .
In her editorial, Mosca points out that "only a handful" of primary-prevention studies were available for analysis, and four of these trials enrolled patients at low risk for cardiovascular events, making it difficult to provide much clarity surrounding the controversy of statin use in women. In addition, the meta-analysis focused on the relative reduction in risk and does not provide data on the absolute benefit of treatment.
If treatment decisions regarding statins are driven by the annual mortality risk of the patient in primary prevention, the absolute risk of cardiovascular disease and corresponding proportional reduction in risk from statin therapy are needed to make "informed clinical choices."
"Only then we will know with less uncertainty whether what is good for the gander is also good for the goose," writes Mosca.