Frailty Increases Risk for Poor Outcomes in HF With Preserved Ejection Fraction

frailty, elderly, disability
frailty, elderly, disability
Researchers sought to determine the efficacy of sacubitril/valsartan in patients with heart failure with preserved ejection fraction and frailty.

Among patients with heart failure with preserved ejection fraction (HFpEF), frailty is common and associated with poorer outcomes. These findings, from a randomized trial, were published in the Journal of the American College of Cardiology.

This study was a post-hoc analysis of data from the Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) trial. Patients (N=4795) with HFpEF were randomly assigned to receive sacubitril and valsartan or valsartan only. In this analysis, risk for heart failure (HF) hospitalization and cardiovascular death were evaluated on the basis of frailty, measured using the Rockwood cumulative deficit approach.

The patients were not frail (n=2165), more frail (n=2084), and the most frail (n=546). Most frail was defined as a frailty index (FI) of 0.311 or higher, more frail as FI between 0.211 and 0.310, and not frail as FI of 0.210 or lower. Stratified by frailty status, the not frail, more frail, and most frail cohorts comprised 52.9%, 51.7%, and 46.9% women (P =.03); were aged mean 71.3, 73.8, and 74.6 years (P <.001); and had left ventricular ejection fraction of 57.6%, 57.5%, and 57.3% (P <.001), respectively.

Patients who were the most frail (rate ratio [RR], 2.19; 95% CI, 1.85-2.60) and more frail (RR, 3.29; 95% CI, 2.65-4.09) had a higher incidence of the composite outcome of HF hospitalization or cardiovascular death compared with the no frailty group. Similar trends were observed for the secondary outcomes of HF hospitalization, cardiovascular death, and all-cause mortality.

No significant effects were observed on outcomes on the basis of intervention medications. However, when FI was used as a continuous variable, a significant interaction between frailty and sacubitril and valsartan was observed (P =.002), suggesting that sacubitril and valsartan had a more beneficial effect compared with valsartan alone among the frail patients.

Frailty was associated with increased risk for adverse events, except for hypotension, which had an inverse relationship with frailty.

This analysis may have been limited by use of the Rockwood approach to define frailty and not muscle strength or functional capacity.

”In PARAGON-HF, greater frailty was associated with more impairment of health status and cognitive function and worse clinical outcomes,” the study authors wrote. “There is a need for more education about the importance of frailty, its assessment, and implications in cardiology.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Butt JH, Dewan P, Jhund PS, et al. Sacubitril/valsartan and frailty in heart failure with preserved ejection fraction: a post-hoc analysis of PARAGON-HF. J Am Coll Cardiol. Published online August 29, 2022.