Abstract 13617: Spironolactone Use is Associated With Better Survival in Heart Failure Patients With Preserved Ejection Fraction With Concomitant Angiotensin Receptor Blocker Treatment

Introduction: The guidelines recommend using renin-angiotensin-aldosterone system inhibitors, including spironolactone and angiotensin II receptor blocker (ARB), and spironolactone rather than angiotensin-converting enzyme inhibitors (ACEI) for treating heart failure with preserved ejection fraction (HFpEF). However, it is unclear whether there is an additive effect of spironolactone when combined with ACEI/ARB on HFpEF.

Hypothesis: Spironolactone combined with ACEI or ARB may provide additional benefits in patients with HFpEF.

Methods: We conducted a post hoc analysis of the TOPCAT (Heart Failure Trial with Aldosterone Antagonist for Preservation of Heart Function) trial using Cox proportional hazards models to evaluate the effect of spironolactone on the clinical prognosis of HFpEF patients, with or without ACEI or ARB. Our primary outcomes were defined as death from cardiovascular causes, aborted cardiac arrest, and hospitalization for heart failure.

Results: A total of 1767 HFpEF patients from the Americas were included (49.9% women, median age 71.5 years). During a median follow-up of 2.98 years, 522 (29.5%) primary outcomes occurred. Compared with placebo, spironolactone use was associated with a lower incidence of primary outcomes (hazard ratio [HR]: 0.69, P=0.02), cardiovascular mortality (HR: 0.45, P=0.004) and all-cause mortality (HR: 0.58, P=0.01) after adjustments in HFpEF patients who were concomitantly taking ARB at baseline but not in those without ARB use. Significant interactions were found between spironolactone use and baseline ARB use for cardiovascular and all-cause death (P=0.01). In contrast, spironolactone use was associated with lower cardiovascular death (HR: 0.59, P=0.01) in patients without ACEI baseline use but not in those with ACEI use. There was no significant interaction observed between spironolactone use and baseline ACEI for adverse outcomes.

Conclusions: Among HFpEF patients enrolled in TOPCAT-Americas, the survival benefit of spironolactone was enhanced by ARB use but not ACEI use. Further prospective studies are necessary to validate these findings.