Abstract

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 pro-spectively. 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 pre-scription 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 prog-nosis associated with physical frailty.