Characteristics and Outcomes of a Real-world Population with Heart Failure with Reduced Ejection Fraction Representative of Clinical Trial Patients

Abstract

Introduction Heart failure with reduced ejection fraction (HFrEF) incurs significant mortality, morbidity and cost. Despite recent advances, opportunities for therapeutic improvement remains. Omecamtiv mecarbil (OM) is a first-in-class cardiac myotrope currently in a phase-3 clinical trial (GALACTIC-HF) for HFrEF treatment. Given known differences between real world (RW) and clinical trial populations, we sought to characterize RW patients who might benefit from OM. Methods In the Vanderbilt University Medical Center de-identified electronic health record of in- and outpatients (Synthetic Derivative) from 2006-2019, we created two RW cohorts of HFrEF patients: 1) Based on the validated eMERGE Network phenotype of HFrEF (left ventricular ejection fraction (LVEF) ≤ 40%; ‘clinical cohort’) and 2) Mirroring eligibility criteria of the GALACTIC-HF trial (LVEF ≤ 35%; ‘GALACTIC-HF-like cohort’) including hospitalizations, medications and laboratory values. Diagnosis and procedure codes, structured and unstructured problem lists, laboratory values, and medications were used to characterize demographics, clinical characteristics and outcomes. HF hospitalization rates were calculated from 5 days post HF index date to last encounter or death. Results The clinical cohort included 3,955 HFrEF patients and the GALACTIC-HF-like cohort included 1,541 (median age at index date 65 and 61 years, respectively), both approximately 67% male and 80% white. Aside from higher median BNP level in the GALACTIC-HF-like cohort, clinical characteristics such as blood pressure and heart rate of the two cohorts were similar. (Table). Comorbidities and utilization of cardiac devices were somewhat higher in the GALACTIC-HF-like cohort including chronic kidney disease (39 v 30%), atrial fibrillation (52 v 48%), and cardiac resynchronization or implantable cardioverter defibrillator (52 v 40%). HF hospitalization rate (per 1000py) was 242 (95% CI 203, 280) in the clinical and 396 (95% CI 350, 442) in the GALACTIC-HF like cohorts during median follow up of 2.7 and 4.1 years, respectively. Conclusions Approximately 40% of RW HFrEF patients met GALACTIC-HF trial criteria, suggesting that RW HFrEF populations may benefit from new therapies such as OM. The higher prevalence of comorbidities and higher rate of HF hospitalization in the GALACTIC-HF-like cohort may indicate a high-need, high-risk population that may achieve better clinical outcomes with OM.