The Frailty Syndrome and Outcomes in the TOPCAT Trial

AIMS: The impact of frailty on outcomes in randomized heart failure with preserved ejection fraction (HFpEF) trials has not been previously reported. This analysis sought to characterize frailty in a large contemporary HFpEF clinical trial cohort and to evaluate its impact on patient relevant outcomes. METHODS AND RESULTS: Using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, a frailty index (FI) was constructed at baseline using 39 clinical, laboratory, and self-reported variables. The relationship between frailty and outcomes and the role of frailty in modulating the benefits of spironolactone were examined in a subset of 1767 TOPCAT patients. For the cohort as a whole (mean age 71.5 years, 49% female), the mean FI at baseline was 0.37 ± 0.11. Four frailty classes were defined ranging from FI < 0.3 to FI ≥ 0.5. Overall, 94% of subjects were considered frail (defined as a FI > 0.21). Mean age was lowest for the most frail class (69 ± 9 years for Class 4; 73 ± 10 years for Class 1; P < 0.001). Body mass index, systolic blood pressure, and pulse pressure all increased as FI increased. Both primary and secondary outcomes increased as frailty severity increased. There was no interaction between frailty class and treatment effect of spironolactone. CONCLUSIONS: Frailty was very common in TOPCAT HFpEF participants. Greater frailty was associated with a higher risk of cardiovascular outcomes and mortality. The benefit of spironolactone on outcomes in TOPCAT was not attenuated by frailty class.