Women with HFrEF live longer but suffer more

Women with heart failure with reduced ejection fraction (HFrEF) live longer than their male counterparts, but those additional years are plagued by a lower quality of life—including greater levels of self-reported anxiety, depression and physical disability—according to an analysis of two randomized HFrEF trials published in the Journal of the American College of Cardiology.

The study encompassed 12,058 men and 3,357 women from the recent PARADIGM-HF and ATMOSPHERE trials, which featured nearly identical inclusion criteria and were designed to evaluate different pharmacological options for patients with HFrEF.

Women in the trials were two years older than men on average and were more often obese (33.4 percent versus 29.2 percent) or hypertensive (70.6 percent versus 65.5 percent). Aside from those conditions, men had the greater burden of comorbidities including atrial fibrillation, coronary artery disease, previous heart attack and stroke.

After covariate adjustment—including for the prognostic biomarker N-terminal pro-B-type natriuretic peptide—women were 32 percent more likely to survive to the end of the studies’ follow-up, which spanned a median 26.6 months in PARADIGM-HF and 36.7 months in ATMOSPHERE. Women were also 20 percent less likely to be hospitalized for heart failure.

However, their scores on the Kansas City Cardiomyopathy Questionnaire, which measures health-related quality of life on a scale of 0 to 100, were a median of 10 points lower (71.3 versus 81.3). In particular, the domains assessing physical limitations and anxiety or depression suffered the most among women; 45 percent of the women reported moderate-to-extreme anxiety or depression.

Women had more symptoms and signs of HFrEF, but were still treated less often with diuretics and anticoagulants, received fewer device implantations and were referred less often to cardiac rehabilitation programs. Implantable cardioverter defibrillators were used in 8.6 percent of women and 16.6 percent of men, while 4.1 percent of women and 6.9 percent of men received cardiac resynchronization therapy devices.

“The lower use of cardiac resynchronization therapy in women is especially notable, as this intervention may be even more effective in women than men and given that left bundle branch block is more common in women, often with a narrower QRS duration than in men,” wrote lead author Pooja Dewan, MBChB, with the University of Glasgow in the United Kingdom, and colleagues. “Women continue to receive suboptimal treatment, compared with men, with no obvious explanation for this shortfall.”

The authors of a related editorial suggested the everyday stressors faced by women could help explain why their symptoms and quality-of-life seemed to suffer more than men’s. Women are prone to having lower incomes and greater caregiving and childcare responsibilities than men, while also being less likely to have a caregiver themselves, they said.

“Clarifying the role of social stressors will ultimately allow improved treatment of men and women,” Mary Norine Walsh, MD, with St. Vincent Heart Center in Indianapolis, and colleagues wrote in the editorial. “We need to better understand how societal inequalities translate to physical symptoms. It is intriguing to postulate that women with HF may have more physical symptoms than men because they have more stress overall in their lives.”

Dewan and coauthors noted these contemporary trials of HFrEF actually showed a narrowing of sex-specific gaps in some treatment areas compared to previous studies. The usage of angiotensin-converting enzyme inhibitors at baseline was nearly as high for women (84.7 percent) as men (88.7 percent), but the gender gap was 5.7 to 8.7 percent in terms of treatment with statins, aspirin and anticoagulants—with greater proportions of men receiving each of those medications.  

“It is not surprising that the authors found that women and men were both well treated with HF-indicated medications, as trial enrollment stipulated such treatment,” Walsh et al. wrote. “But the continued demonstration of undertreatment of women with other pharmacological, device, and exercise therapies even in the setting of randomized trials is appalling. … If patients in the care of experienced investigators remain undertreated and inadequately referred, the average patient faces impossible odds.”

The editorialists also took issue with only 21 percent of the participants enrolled in the trials being women. And the explanation that HFrEF is less common in women isn’t good enough, they said; epidemiologic data suggests that up to 40 percent of women with heart failure have HFrEF. Different strategies may be needed to recruit more women for clinical trials, but the payoff will be worth it, Walsh and coauthors predicted.

“Women must be enrolled in research trials in adequate numbers, subgroup endpoints must be prespecified, analyzed, and required for publication by journal editors and reviewers of manuscripts,” they wrote. “Only with these measures will we be able to offer all our patients, both women and men, diagnostic and therapeutic strategies that are patient-centric and optimally beneficial.”