Epidemiology of Worsening Heart Failure in a Population-based Cohort from Alberta, Canada: Evaluating Eligibility for Treatment With Vericiguat

•Worsening heart failure (WHF) is of increasing interest with newer therapies, including the guanylate cyclase stimulator, vericiguat, developed for this population. The epidemiology of WHF in broad populations is uncertain.•In a population-based study of an entire region of 3.1 million adults with a single integrated health authority, approximately one-half of the patients with heart failure and reduced ejection fraction experienced WHF and 38.3% were potentially eligible for vericiguat therapy.•Guideline-directed medical therapies were still underused in patients with heart failure and reduced ejection fraction, highlighting the need for further initiatives to address this persistent care gap. Patients with heart failure (HF) and a reduced ejection fraction (HFrEF) who experience worsening HF (WHF) events are at increased risk of adverse outcomes and experience significant morbidity and mortality. We herein describe the epidemiology of these patients and identify those potentially eligible for vericiguat therapy in this population-based study. This retrospective cohort study included hospitalized or emergency department patients with a primary diagnosis of HF and a left ventricular ejection fraction (LVEF) of less than 45% diagnosed between April 1, 2009, and March 31, 2019 in Alberta, Canada, with follow-up to March 31, 2020. Inclusion criteria from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection (VICTORIA) trial were applied to explore eligibility for vericiguat. Among 25,629 patients with HF and LVEF data, 9948 (38.8%) had HFrEF, of which 5259 (52.8%) experienced WHF at some point during a median 5.8 years of follow-up, and 38.3% of those met the vericiguat trial eligibility criteria. Compared with patients with HFrEF without WHF, those with WHF were older, with more comorbidities, worse renal function, and similar LVEF status, but greater use of HF medications at baseline. At the time of WHF, 27% of those with HFrEF and WHF were on triple therapy, 50.6% were on dual therapy, and 15.4% were on monotherapy. All-cause mortality and the composite outcome of all-cause mortality or cardiovascular hospitalization at 1-year of follow-up were higher in the HFrEF with WHF cohort compared with HFrEF without WHF (adjusted hazard ratios of 1.92 and 1.51, respectively, both P < .0001). Approximately one-half of patients with HFrEF experienced WHF over the long-term follow-up. Most were not on triple therapy, highlighting the underu