BACKGROUND Guideline-recommended therapies that improve prognosis remain underused in clinical practice. Physical frailty may lead to underprescription of life-saving therapy. We aimed to investigate the association between physical frailty and the use of evidence-based pharmacological therapy for heart failure with reduced ejection fraction and the impact of this on prognosis. METHODS AND RESULTS The FLAGSHIP (Multicentre Prospective Cohort Study to Develop Frailty-Based Prognostic Criteria for Heart Failure Patients) included patients hospitalized for acute heart failure, and data on physical frailty were collected prospectively. We analyzed 1041 patients with heart failure with reduced ejection fraction (aged 70 years; 73% male) and divided them by physical frailty categories using grip strength, walking speed, Self-Efficacy for Walking-7 score, and Performance Measures for Activities of Daily Living-8 score: categories I (n=371; least frail), II (n=275), III (n=224), and IV (n=171). Overall prescription rates of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists were 69.7%, 87.8%, and 51.9%, respectively. The proportion of patients receiving all 3 drugs decreased as physical frailty increased (in category I patients, 40.2%; IV patients, 23.4%; P for trend<0.001). In adjusted analyses, the severity of physical frailty was an independent predictor for nonuse of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio [OR], 1.23 [95% CI, 1.05-1.43] per 1 category increase) and β-blockers (OR, 1.32 [95% CI, 1.06-1.64]), but not mineralocorticoid receptor antagonists (OR, 0.97 [95% CI, 0.84-1.12]). Patients receiving 0 to 1 drug had a higher risk of the composite outcome of all-cause death or heart failure rehospitalization than those treated with 3 drugs in physical frailty categories I and II (hazard ratio [HR], 1.80 [95% CI, 1.08-2.98]) and III and IV (HR, 1.53 [95% CI, 1.01-2.32]) in the multivariate Cox proportional hazard model. CONCLUSIONS Prescription of guideline-recommended therapy decreased as severity of physical frailty increased in heart failure with reduced ejection fraction. Underprescription of guideline-recommended therapy may contribute to the poor prognosis associated with physical frailty.
Keywords: drug therapy; frailty; heart failure; prognosis; reduced ejection fraction.