Key result
Aerobic exercise training reduced the risk of all-cause hospitalization or mortality in frail patients with HFrEF (HR 0.83; 95% CI 0.72-0.95), with baseline frailty modifying the treatment effect.
Why the study?
Frailty is common and associated with adverse outcomes in HFrEF, but whether baseline frailty modifies the efficacy of aerobic exercise training was not known.
Does aerobic exercise training reduce all-cause hospitalization or mortality in stable outpatients with HFrEF, and is this effect modified by baseline frailty?
RCT (n=2,130)
randomized
Does aerobic exercise training reduce all-cause hospitalization or mortality in stable outpatients with HFrEF, and is this effect modified by baseline frailty?
Hazard Ratio: 0.83 (95% CI 0.72–0.95)
p-value: p=0.04 for interaction
Aerobic exercise training significantly reduces the risk of all-cause hospitalization in frail, but not nonfrail, patients with HFrEF.
Supports aerobic exercise training in frail HFrEF outpatients; extends prior trials by showing frailty modifies benefit.
Background: Supervised aerobic exercise training (ET) is recommended for stable outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Frailty, a syndrome characterized by increased vulnerability and decreased physiologic reserve, is common in patients with HFrEF and associated with a higher risk of adverse outcomes. The effect modification of baseline frailty on the efficacy of aerobic ET in HFrEF is not known. Methods: Stable outpatients with HFrEF randomized to aerobic ET versus usual care in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were included. Baseline frailty was estimated using the Rockwood frailty index (FI), a deficit accumulation–based model of frailty assessment; participants with FI scores >0.21 were identified as frail. Multivariable Cox proportional hazard models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether frailty modified the treatment effect of aerobic ET on the primary composite end point (all-cause hospitalization or mortality), secondary end points (composite of cardiovascular death or cardiovascular hospitalization, and cardiovascular death or HF hospitalization), and Kansas City Cardiomyopathy Questionnaire score. Separate models were constructed for continuous (FI) and categorical (frail versus not frail) measures of frailty. Results: Among 2130 study participants (age, 59±13 years; 28% women), 1266 (59%) were characterized as frail (FI>0.21). Baseline frailty burden significantly modified the treatment effect of aerobic ET ( P interaction: FI × treatment arm=0.02; frail status [frail versus nonfrail] × treatment arm=0.04) with a lower risk of primary end point in frail (hazard ratio [HR], 0.83 [95% CI, 0.72–0.95]) but not nonfrail (HR, 1.04 [95% CI, 0.87–1.25]) participants. The favorable effect of aerobic ET among frail participants was driven by a significant reduction in the risk of all-cause hospitalization (HR, 0.84 [95% CI, 0.72–0.99]). The treatment effect of aerobic ET on all-cause mortality and other secondary endpoints was not different between frail and nonfrail patients ( P interaction>0.1 for each). Aerobic ET was associated with a nominally greater improvement in Kansas City Cardiomyopathy Questionnaire scores at 3 months among frail versus nonfrail participants without a significant treatment interaction by frailty status ( P interaction>0.2). Conclusions: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of aerobic ET with a greater reduction in the risk of all-cause hospitalization but not mortality.
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Pandey et al. (2022) conducted an RCT in chronic heart failure and reduced ejection fraction (n=2,130). Aerobic exercise training vs. usual care was evaluated on all-cause hospitalization or mortality (HR 0.83, 95% CI 0.72-0.95, p=0.04 for interaction). Aerobic exercise training reduced the risk of all-cause hospitalization or mortality in frail patients with HFrEF (HR 0.83; 95% CI 0.72-0.95), with baseline frailty modifying the treatment effect.
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