3C-06 - Mortality and hospitalization rates of adults with stable, chronic heart failure with reduced ejection fraction in the US, a claims analysis to inform clinical trial background rates

Background: Heart failure (HF) is commonly classified as HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF). While existing literature often focuses on mortality and hospitalization rates following acute HF decompensation or hospitalization, less is known about these outcomes in individuals with stable, chronic HFrEF free of recent decompensation. To support the understanding of background rates, we identified a stable, chronic HFrEF population based on key inclusion criteria of a clinical trial.

Objectives: This study aimed to estimate the mortality and hospitalization rates among individuals with stable, chronic HFrEF to contextualize potential adverse events in a trial.

Methods: This retrospective cohort study utilized the US Optum claims database. Adults with ≥2 validated HFrEF diagnosis codes in an outpatient setting for 1-12 months apart from 2018/10/1 to 2023/9/30 were included (cohort entry: the second HFrEF diagnosis date). Individuals were required to have 1-year continuous insurance enrollment (baseline) before cohort entry. Individuals with any hospitalization in the 6 months prior to cohort entry or severe chronic kidney disease were excluded. Demographic characteristics and baseline comorbidities were described. Outcomes included mortality (all-cause) and hospitalizations (all-cause, cardiovascular disease [CVD]-related, and HF-related). Cumulative incidence proportions were estimated using the Kaplan-Meier method. Individuals were followed from cohort entry to event or censor date (mortality, insurance disenrollment, 1-year follow-up, or end of the study period). Analyses were stratified by age groups (16-64, 65-74, and ≥75 years [y]).

Results: The study included 101,377 individuals with stable, chronic HFrEF. The median age at cohort entry was 75 years (16-64y: 16.5%, 65-74y: 31.4%, ≥75y: 52.1%), 38.4% were female, and 70.8% were non-Hispanic White. The baseline comorbidity burden was high, including hypertension (84.0%), dyslipidemia (78.4%), diabetes (43.5%), and atrial fibrillation/flutter (43.3%). The 1-year all-cause mortality was 10.6% (16-64 y: 4.9%, 65-74y: 7.0%, ≥75y: 14.4%), all-cause hospitalization was 32.7% (26.5%, 29.2%, 36.6%), CVD-related hospitalization was 22.0% (17.7%, 19.8%, 24.6%), and HF-related hospitalization was 9.9% (7.8%, 8.3%, 11.5%).

Conclusions: Compared to published rates for acute HFrEF, this study found lower mortality and hospitalization rates in a stable, chronic HFrEF population at comparable ages. Given that trials often enroll less severe disease populations, utilizing trial-specific background rates is critical for accurately interpreting the safety profiles of drugs in development.