European Primary Care Cardiovascular Society

Women with HFrEF show lower outcome rates but more symptoms, lower QoL and undertreatment compared to men

Differential Impact of Heart Failure With Reduced Ejection Fraction on Men and Women

Literature - Dewan P, Rørth R, Jhund PS et al. - JACC 2019; 73(1): 29-40

Introduction and methods

Heart failure (HF) trials initiated in the last century highlighted many differences between men and women [1-8], including undertreatment in women compared to men [1-13], which has led to changed assessment and management of patients with HF. These changes may give a new perspective on the management of, and outcomes in, women with HF with reduced ejection fraction (HFrEF). This analysis compared women (n=3.357) and men (n=12.058) with HF enrolled in the two most recent and largest randomized trials of pharmacological therapy in patients with HFrEF.

The Prospective comparison of ARNI [Angiotensin Receptor Neprilysin Inhibitor] with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) and Aliskiren Trial to Minimize OutcomeS in Patients with Heart failure (ATMOSPHERE) trials included HF patients aged ≥18 years with NYHA functional class II to IV, LVEF ≤35%, plasma B-type natriuretic peptide ≥150 pg/mL or NT-pro-BNP ≥600 pg/mL, taking an ACE inhibitor or ARB, beta-blocker, and MRA if indicated. The median follow-up was 26.6 months in the PARADIGM-HF trial and 36.6 months in the ATMOSPHERE trial.

In this analysis, the primary outcome for both trials was studied, consisting of the composite of first HF hospitalization or CV mortality, in women compared with men. Also the components of the primary outcome, sudden death, pump failure death, non-CV death, and all-cause death, and recurrent hospitalizations were compared between women and men. Health-related quality of life (HRQL) was measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, with lower scores indicating a poorer HRQL. General quality of life (QoL) was measured using the EQ-5D-3L questionnaire in the PARADIGM-HF trial.

Main results

Gender and pre-existing comorbidities

Gender and HF characteristics and investigations at baseline

Gender and treatment at baseline

Gender and clinical outcomes

Gender and recurrent events


An analysis of the PARADIGM-HF and ATMOSPHERE trials with HFrEF patients showed lower rates of HF hospitalization and CV mortality in women, however, they had more symptoms and worse HQRL, compared to men. Further, women appeared relatively undertreated with diuretics, anticoagulants and devices given their greater evidence of congestion, and they were less often referred to a disease management program or prescribed for an exercise regimen. These data suggest tailored therapeutic strategies for women, increased referral to cardiac rehabilitation programs, and more psychosocial support.


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