Table 1.
Sex differences in recent HFpEF treatment trials.
| Trial (year) | Number of patients | % female | Intervention | EF cut-off | Type of analysis | Baseline differences (women versus men) | Sex-specific results |
|---|---|---|---|---|---|---|---|
| TOPCAT (2019) | 1767 | 49.9% | Spironolactone | 45% | Post hoc, non-pre-specified | Older Fewer comorbidities Higher LVEF, BP, BMI Lower GFR, Hgb Higher NYHA class Lower KCCQ score |
• Rates of primary outcome and HF hospitalization not different • Significant reduction in all-cause mortality w/spironolactone in women (HR 0.66; 95% CI: 0.48–0.9; p = 0.01), but not in men; sex-treatment interaction p = 0.024. |
| PARAGON-HF (2020) | 4796 | 51.7% | Sacubitril-valsartan | 45% | Prespecified subgroup | Older More obesity Fewer comorbidities Lower median NT-proBNP level Lower GFR Higher LVEF Higher NYHA class Lower KCCQ score Less likely on MRA |
• In control group, women had higher rates of HF hospitalization and lower rates of CV death • Rate ratio for primary outcome was 0.73 (95% CI: 0.59–0.90) in women and 1.03 (95% CI: 0.84–1.25) in men with p interaction = 0.017, predominately related to HF hospitalization (33% RRR, p interaction = 0.005) |
| EMPEROR-PRESERVED (2021) | 5988 | 44.7% | Empagliflozin | 40% | Prespecified subgroup | – | • No difference between women and men • HR for male: 0.81 (95% CI: 0.69–0.96) and for female: 0.75 (95% CI: 0.64–0.92) |
| DELIVER (2022) | 6263 | 43.9% | Dapagliflozin | 40% | Prespecified subgroup | – | • No difference between women and men • HR for male: 0.82 (95% CI: 0.71–0.96) and for female: 0.81 (95% CI: 0.67–0.97) |
Summary of sex-specific results in recent HFpEF treatment trials, including TOPCAT, PARAGON-HF, and EMPEROR-PRESERVED.
TOPCAT: Treatment of Preserved Cardiac Function Heart Failure with Aldosterone Antagonist; PARAGON-HF: Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction; EMPEROR-PRESERVED: Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction; EF: ejection fraction; CAD: coronary artery disease; AF: atrial fibrillation; COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; BP: blood pressure; BMI: body mass index; GFR: glomerular filtration rate; Hgb: hemoglobin; NYHA: New York Heart Association; KCCQ: Kansas City Cardiomyopathy Questionnaire; NT-proBNP: N-terminal pro brain natriuretic peptide; MRA: mineralocorticoid; HR: hazard ratio; CI: confidence interval; RRR: relative risk reduction.