Prognostic significance of medical therapy in patients with heart failure with reduced ejection fraction

AIMS: The use of guideline‐directed medical therapy (GDMT) among patients with heart failure (HF) with reduced ejection fraction (HFrEF) remains suboptimal. The SMYRNA study aims to identify the clinical factors for the non‐use of GDMT and to determine the prognostic significance of GDMT in patients with HFrEF in a real‐life setting. METHODS AND RESULTS: The SMYRNA study is a prospective, multicentre, and observational study that included outpatients with HFrEF. Patients were divided into three groups according to the status of GDMT at the time of enrolment: (i) patients receiving all classes of HF medications including renin‐angiotensin system (RAS) inhibitors, beta‐blockers, and mineralocorticoid receptor antagonists (MRAs); (ii) patients receiving any two classes of HF medications (RAS inhibitors and beta‐blockers, or RAS inhibitors and MRAs, or beta‐blockers and MRAs); and (iii) either patients receiving class of HF medications (only one therapy) or patients not receiving any class of HF medications. The primary outcome was a composite of hospitalization for HF or cardiovascular death. The study population consisted of 1062 patients with HFrEF, predominantly men (69.1%), with a median age of 68 (range: 20–96) years. RAS inhibitors, beta‐blockers, and MRAs were prescribed in 76.0%, 89.4%, and 55.1% of the patients, respectively. The proportions of patients receiving target doses of guideline‐directed medications were 24.4% for RAS inhibitors, 11.0% for beta‐blockers, and 11.1% for MRAs. Overall, 491 patients (46.2%) were treated with triple therapy, 353 patients (33.2%) were treated with any two classes of HF medications, and 218 patients (20.6%) were receiving only one class of HF medication or not receiving any HF medication. Patient‐related factors comprising older age, New York Heart Association functional class, rural living, presence of hypertension, and history of myocardial infarction were independently associated with the use or non‐use of GDMT. During the median 24‐month period, the primary composite endpoint occurred in 362 patients (34.1%), and 177 of 1062 (16.7%) patients died. Patients treated with two or three classes of HF medications had a decreased risk of hospitalization for HF or cardiovascular death compared with those patients receiving ≤1 class of HF medication [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.49–0.85; P = 0.002, and HR: 0.61; 95% CI: 0.47–0.79; P < 0.001, respectively]. CONCLUSIONS: The real‐life SMYRNA study provided comprehensive data about the clinical factors associated with the non‐use of GDMT and showed that suboptimal GDMT is associated with an increased risk of hospitalization for HF or cardiovascular death in patients with HFrEF.