Frailty, Guideline-Directed Medical Therapy, and Outcomes in HFrEF: From the GUIDE-IT Trial.

Abstract

OBJECTIVES:

In this study, we sought to evaluate the association of frailty with the use of optimal guideline-directed medical therapy (GDMT) and outcomes in heart failure with reduced ejection fraction (HFrEF).

BACKGROUND:

The burden of frailty in HFrEF is high, and the patterns of GDMT use according to frailty status have not been studied previously.

METHODS:

A post hoc analysis of patients with HFrEF enrolled in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial was conducted. Frailty was assessed with the use of a frailty index (FI) using a 38-variable deficit model, and participants were categorized into 3 groups: class 1: nonfrail, FI <0.21); class 2: intermediate frailty, FI 0.21-0.31), and class 3: high frailty, FI >0.31). Multivariate-adjusted Cox models were used to study the association of frailty status with clinical outcomes. Use of optimal GDMT over time (beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists) across frailty strata was assessed with the use of adjusted linear and logistic mixed-effect models.

RESULTS:

The study included 879 participants, of which 56.3% had high frailty burden (class 3 FI). A higher frailty burden was associated with a significantly higher risk of HF hospitalization or death in adjusted Cox models: high frailty vs nonfrail HR: 1.76, 95% CI: 1.20-2.58. On follow-up, participants with high frailty burden also had a significantly lower likelihood of achieving optimal GDMT: high frailty vs non-frail GDMT triple therapy use at study end: 17.7% vs 28.4%; P interaction, frailty class × time <0.001.

CONCLUSIONS:

Patients with HFrEF with a high burden of frailty have a significantly higher risk for adverse clinical outcomes and are less likely to be initiated and up-titrated on an optimal GDMT regimen.

• Authors: Muhammad Shahzeb Khan, Matthew W Segar, Muhammad Shariq Usman, Sumitabh Singh, Stephen J Greene, Gregg C Fonarow, Stefan D Anker, G Michael Felker, James L Januzzi Jr, Javed Butler, Ambarish Pandey
• Journal: JACC. Heart failure (JACC Heart Fail) Vol. 10 Issue 4 Pg. 266-275 (04 2022) ISSN: 2213-1787 [Electronic] United States
• PMID: 35361446 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Mineralocorticoid Receptor Antagonists

Topics

• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Frailty (complications, epidemiology)
• Heart Failure (drug therapy)
• Humans
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Stroke Volume