Frailty modifies treatment effect of exercise training in patients with chronic stable HFrEF

For frail patients with chronic stable heart failure (HF) with reduced ejection fraction (HFrEF), aerobic exercise training confers significant reduction in the risk of all-cause hospitalization but not mortality, a study reports.

The study used data from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial, which randomized stable outpatients with HFrEF to undergo either aerobic ET or usual care. Baseline frailty was estimated using the Rockwood frailty index (FI), a model of frailty assessment based on deficit accumulation; participants with FI scores >0.21 were identified as frail.

Of the 2,130 participants (mean age 59 years, 28 percent women) included in HF-ACTION, 1,266 (59 percent) were characterized as frail (FI>0.21). Frail participants had more cardiometabolic comorbidities, worse symptom burden, poorer functional status, and higher burden of HF hospitalization at baseline compared with nonfrail participants.

Multivariable Cox proportional hazard models showed that baseline frailty significantly modified the treatment effect of aerobic exercise training, such that the primary composite endpoint of the risk of all-cause hospitalization or mortality was reduced among frail participants (hazard ratio [HR], 0.83, 95 percent confidence interval [CI], 0.72–0.95) but remained unchanged among those who were nonfrail (HR, 1.04, 95 percent CI, 0.87–1.25).

The beneficial effect of aerobic exercise training among frail participants was driven by a significant reduction in the risk of all-cause hospitalization (HR, 0.84, 95 percent CI, 0.72–0.99). Meanwhile, the treatment effect of the intervention on all-cause mortality and other secondary endpoints was similar between frail and nonfrail participants.

Aerobic exercise training yielded a numerically greater improvement in Kansas City Cardiomyopathy Questionnaire scores at 3 months among frail vs nonfrail participants without a significant treatment interaction by frailty status.

The findings indicate that baseline frailty may identify HFrEF patients who are more likely to benefit from supervised aerobic exercise training.