Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction.

Abstract

BACKGROUND:

Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk-benefit profile is perceived to be less favorable than in nonfrail patients.

OBJECTIVES:

This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.

METHODS:

Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death.

RESULTS:

A frailty index (FI) was calculable in 4,795 patients. In total, 45.2% had class 1 frailty (FI ≤0.210, not frail), 43.5% had class 2 frailty (FI 0.211-0.310, more frail), and 11.4% had class 3 frailty (FI ≥0.311, most frail). There was a graded relationship between FI class and the primary endpoint, with a significantly higher risk associated with greater frailty (class 1: reference; class 2 rate ratio: 2.19 [95% CI: 1.85-2.60]; class 3 rate ratio: 3.29 [95% CI: 2.65-4.09]). The effect of sacubitril/valsartan vs valsartan on the primary endpoint from lowest to highest FI class (as a rate ratio) was: 0.98 [95% CI: 0.76-1.27], 0.92 [95% CI: 0.76-1.12], and 0.69 [95% CI: 0.51-0.95]), respectively (Pinteraction = 0.23). When FI was examined as a continuous variable, the interaction with treatment was significant for the primary outcome (Pinteraction = 0.002) and total heart failure hospitalizations (Pinteraction < 0.001), with those most frail deriving greater benefit.

CONCLUSIONS:

Frailty was common in heart failure with preserved ejection fraction and associated with worse outcomes. Compared with valsartan, sacubitril/valsartan seemed to show a greater reduction in the primary endpoint with increasing frailty, although this was not significant when FI was examined as a categorical variable. (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

• Authors: Jawad H Butt, Pooja Dewan, Pardeep S Jhund, Inder S Anand, Dan Atar, Junbo Ge, Akshay S Desai, Luis E Echeverria, Lars Køber, Carolyn S P Lam, Aldo P Maggioni, Felipe Martinez, Milton Packer, Jean L Rouleau, David Sim, Dirk J Van Veldhuisen, Bojan Vrtovec, Faiez Zannad, Michael R Zile, Jianjian Gong, Martin P Lefkowitz, Adel R Rizkala, Scott D Solomon, John J V McMurray
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 80 Issue 12 Pg. 1130-1143 (09 20 2022) ISSN: 1558-3597 [Electronic] United States
• PMID: 36050227 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Biphenyl Compounds
• Drug Combinations
• Tetrazoles
• sacubitril
• Valsartan

Topics

• Aminobutyrates (pharmacology, therapeutic use)
• Angiotensin Receptor Antagonists (pharmacology, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Drug Combinations
• Frailty
• Heart Failure (drug therapy)
• Humans
• Stroke Volume
• Tetrazoles (pharmacology, therapeutic use)
• Valsartan