Sex differences in clinical characteristics and outcomes in elderly patients with heart failure and preserved ejection fraction: the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial

Abstract

Background: There are few sex-specific outcome data in heart failure with preserved ejection fraction.

Methods and results: We assessed sex differences in baseline characteristics and outcomes among 4128 patients with heart failure with preserved ejection fraction in the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Women (n=2491) with heart failure with preserved ejection fraction were ≈1 year older (72±7 years versus 71±7 years) and more likely to be obese (46% versus 35%) and have chronic kidney disease (34% versus 26%) and hypertension (91% versus 85%) than men but less likely to have an ischemic cause (19% versus 34%), atrial fibrillation (27% versus 33%), or chronic obstructive pulmonary disease (8% versus 13%) (all P<0.001). During a mean of 49.5 months, there were 881 deaths (447 in women, 434 in men; risk ratio, 0.64; 95% CI, 0.56-0.74) and 5776 hospitalizations (3239 in women, 2537 in men; risk ratio, 0.80; 95% CI, 0.76-0.84). Women had lower risk of all-cause events (deaths and hospitalizations), even after adjusting for baseline characteristics (adjusted hazards ratio, 0.81; 95% CI, 0.73-0.89). However, the sex-related difference in risk of all-cause events was modified in the presence or absence of atrial fibrillation, renal dysfunction, stable angina pectoris, or advanced New York Heart Association class symptoms.

Conclusions: In patients with typical heart failure with preserved ejection fraction, there were prominent sex differences in baseline characteristics and outcomes. Women had better overall prognosis, although the presence of 4 common baseline characteristics seemed to moderate this finding.

Trial registration: ClinicalTrials.gov NCT00095238.

Figure 1

Association between sex and time to first event. Hazard ratios (HRs) for women versus men for first events, where HR <1 indicates lower risk in women. Event categories include the following: all cause (all-cause death or hospitalization); I-PRESERVE (the primary outcome of the Irbesartan in Heart Failure with Preserved Ejection Fraction trial, which was all-cause death or hospitalization for protocol-specified cardiovascular cause, including heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke); CV (cardiovascular events); and non-CV (noncardiovascular events). Black circles and lines represent unadjusted HR and 95% CI. Gray squares and lines represent HR and 95% CI adjusted for age, obesity, New York Heart Association status, heart failure (HF) cause, HF hospitalization within 6 months, comorbidities/risk factors (history of hypertension, stable angina pectoris, myocardial infarction, percutaneous coronary intervention/coronary artery bypass surgery, atrial fibrillation, diabetes mellitus, stroke/transient ischemic attack, chronic obstructive lung disease, valve disease, smoking), ejection fraction, heart rate, systolic blood pressure, hemoglobin, N-terminal pro-B-type natriuretic peptide, neutrophil count, glomerular filtration rate, and medications.

Figure 2

Effect of interactions on association between sex and all-cause events. The y axis indicates hazards ratios (HRs) for women versus men for all-cause events where HR <1 indicates lower risk in women. A, Results of univariable analyses showing the HRs in the absence (black) or presence (gray) of specific risk factors, including New York Heart Association (NYHA) class 3 or 4, stable angina pectoris (SAP), atrial fibrillation (AF), and reduced estimated glomerular filtration rate (eGFR). B, Results of multivariable analyses accounting for all 4 significant interactions and adjusting for age, obesity, NYHA status, heart failure (HF) cause, HF hospitalization within 6 months, comorbidities/ risk factors (history of hypertension, SAP, myocardial infarction, percutaneous coronary intervention/ coronary artery bypass surgery, AF, diabetes mellitus, stroke/transient ischemic attack, chronic obstructive lung disease, valve disease, smoking), ejection fraction, heart rate, systolic blood pressure, hemoglobin, N-terminal pro-B-type natriuretic peptide, neutrophil count, glomerular filtration rate, and medications. The table (bottom) indicates situations where specific risk factors are present (cross) or absent (tick) at levels of estimated eGFR of 70 mL/min per 1.73 m² (black circles), 60 mL/min per 1.73 m² (gray squares), and 50 mL/min per 1.73 m² (black triangles).