Women with heart failure (HF) have a lower risk of death than their male counterparts, regardless of ejection fraction (EF), according to a meta-analysis published March 8 in the European Journal of Heart Failure. The analysis, based on data on nearly 42,000 patients, is said to be the largest assessment yet of gender and mortality risk in HF.
Manuel Martinez-Selles, MD, of the cardiology department at Hospital General Universitario Gregorio Maranon in Madrid, Spain, and colleagues noted that randomized clinical trials fail to accurately reflect the proportion of women who have HF. Older age or HF with preserved EF are more prevalent in women, and also may be exclusion criteria in trials. Previous studies, some of which were based on small numbers of patients, have had conflicting results.
Martinez-Selles and colleagues aggregated data from 31 randomized and observational studies from the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) individual patient meta-analysis for their assessment. They used Cox proportional hazards models to estimate the risk of death from any cause within three years for men vs. women.
Of the 41,949 patients in the study, 33 percent were women. In their analysis, the researchers found that women compared with men were older (70.5 percent vs. 65.6 percent); more commonly had a history of hypertension (49.9 percent vs. 40 percent); but less commonly had a reduced EF (62.6 percent vs. 81.6 percent). Women also were less likely to be prescribed angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and beta-blockers when compared with men.
In the three-year follow-up, 25.3 percent of women and 25.7 percent of men died. In an analysis adjusted for age, men were found to be at a higher risk for death. Men still had a higher mortality risk after the researchers excluded trials for pharmacotherapy from the analysis. What’s more, the higher mortality risk for men was seen whether they had reduced or preserved EF.
The survival benefit associated with female gender appeared to be stronger in patients with non-ischemic HF, but men and women with diabetes were at equal risk for death from any cause.
“The current analysis suggests that while crude unadjusted mortality rates in men and women were very similar, when adjusted for age the risk of death was higher in men than in women with HF,” they wrote. “Further, the influence of age on survival was similar in men and women, suggesting that better survival in women is associated with factors other than age.”
The data showed that 79 percent of women with reduced EF vs. 84.6 percent of men with reduced EF received ACE inhibitors or ARBs, and 36.2 percent of women with reduced EF vs. 39.7 percent of men with reduced EF were prescribed beta-blockers.
“Perhaps surprisingly, this was particularly evident in patients with reduced EF, where the evidence for these therapies is strongest,” Martinez-Selles and colleagues wrote. “In fact, for all age groups with reduced EF, women received ACE inhibitors or ARBs less frequently than men. Given this pattern of prescribing, the lower risk of death for women compared with men is all the more remarkable.”
The meta-analysis reflected the limitations within individual studies, the authors acknowledged, but they argued that limitation may be countered by the overall breadth of the data.