Sex differences in long-term outcomes among hospitalized heart failure patients across the spectrum of ejection fraction: findings from the Get with the guidelines - heart failure registry

Abstract Background Sex differences in 5-year outcomes across heart failure (HF) ejection fraction (EF) subtypes are not well known. Purpose To assess the interaction between sex and EF for risk of long-term adverse outcomes after hospitalization with HF. Methods Patients from American Heart Association’s Get With The Guidelines – Heart Failure registry enrolled between 1/1/2006 – 12/31/2014 with age ≥ 65 years with available 5-year follow-up data, ascertained through linkage with Medicare fee-for-service Part A administrative claims, were included. HF subtypes included HF with reduced EF (HFrEF) with EF ≤ 40%, HF with mildly reduced EF (HFmrEF) with EF 41-49%, and HF with preserved EF (HFpEF) with EF ≥ 50%. Sex differences in 5-year all-cause mortality and readmission for each HF subtype were assessed using unadjusted cumulative incidence methods and adjusted Cox models. Median survival across HF subtypes was compared to median survival of U.S. adults. Results 155,670 patients (mean age 81 years, 53.4% females) were included. Male patients were younger and had a higher prevalence of prior myocardial infarction or coronary artery bypass graft surgery and were more likely to have HFrEF, while women were more likely to have history of hypertension and HFpEF. The median post-hospitalization survival of patients with HF was substantially lower than the age- and sex-specific U.S. life expectancy across each HF subtype (Figure 1).Patients with HF had high 5-year mortality rates (HFrEF male: 81.3%, female: 78.4%; HFpEF male: 80.5% vs female 79.5%). In adjusted analysis, female (vs. male) patients had a significantly lower 5-year mortality risk (HR [95%CI]: 0.89 [0.87 – 0.90], p<0.01) and a higher 5-year readmission risk (all-cause: 1.03 [1.02 – 1.04]), CV: 1.05 [1.04 – 1.07]), HF: 1.06 [1.04 – 1.08], p<0.01 for each). HF subtype modified the association between sex and 5-year outcomes (pinteraction <0.05 for mortality and CV and HF readmission), with the greatest risk reduction of mortality for female vs. male patients with HFrEF and the greatest risk increase of readmission (CV and HF) among female vs. male patients with HFmrEF and HFpEF (Figure 2). Conclusion Among patients with HF, the overall survival post-HF hospitalization is very low for each HF subtype. Female patients have a lower 5-year mortality risk but a higher risk of HF or CV readmission regardless of EF.Figure 1Figure 2

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