Guideline-directed medical therapy not good enough for Highly Frail Patients with HFrEF

For patients with chronic HFrEF, contemporary therapy includes multiple medications proven to decrease mortality and hospitalization rates in large randomized controlled trials. Despite proven benefits and strong guideline recommendations, medication use and dosing in routine clinical practice have traditionally fallen short of levels achieved in clinical trials. A better understanding of current practice patterns, gaps in medication delivery, and barriers to receiving guideline-directed medical therapy (GDMT) are critical to the development of targeted initiatives aimed at improving patient outcomes and quality of care. Therefore, Dr Muhammad Shahzeb Khan and his team conducted a study to evaluate the association of frailty with the use of optimal GDMT and outcomes in HFrEF.

In a post hoc analysis, the researchers included 879 patients with HFrEF from the GUIDE-IT trial. They assessed frailty with the use of a frailty index (FI) using a 38-variable deficit model and categorized patients into the following 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).

They used multivariate-adjusted Cox models to study the association of frailty status with clinical outcomes. They assessed the use of optimal GDMT over time (beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists) across frailty strata with the use of adjusted linear and logistic mixed-effect models.

Key findings of the study:

• Among 879 patients, the researchers observed that56.3% had high frailty burden (class 3 FI).
• Upon adjusted Cox models, comparing high frailty and non-frail, they found that a higher frailty burden was associated with a significantly higher risk of HF hospitalization or death (HR: 1.76).
• On follow-up, they noted that the patients 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%.

The authors concluded, "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."

In an accompanying editorial, Dr Nathan Mewton and Dr Laurent Sebbag wrote, "We do exactly the opposite of what we are supposed to do in patients that need it the most."

They wrote that this study provides, "encouragement to challenge the way we optimize HF therapies in our patients on a daily basis, On every visit we should seize the opportunity for optimization."

They further added, "Frailty should not be treated through HF drugs only, and the recent results from REHAB-HF (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients) clearly pave the way towards improvement in quality-of-life outcomes that should be our primary goal in frail HF patients."

For further information:

DOI:10.1016/j.jchf.2021.12.004

Keywords: guideline-directed medical therapy, heart failure with reduced ejection fraction, GDMT regimen, HFrEF, Frailty, poor clinical outcomes, GUIDE-IT trial, heart failure, frailty index, JACC: Heart Failure