Heart Failure Incidence and Risk Factors in U.S. Adults Receiving Bezlotoxumab: A Large Database Analysis

Background: Bezlotoxumab is used to prevent recurrent Clostridioides difficile infection. Although well tolerated, heart failure (HF) exacerbations have been reported as adverse events in clinical trials. This study evaluates the incidence and predictors of HF exacerbation following bezlotoxumab. Methods: We used the TriNetX research database to identify U.S. adults who received bezlotoxumab and stratified them into three groups based on HF history: no HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). The 90-day cumulative incidence of HF events and mortality were assessed. Cox proportional hazard models identified predictors of HF events. Results: Among 2515 patients, 89% had no HF history, 4% had HFpEF, and 7% had HFrEF. The 90-day HF event rates were 1%, 29%, and 52% for the no HF, HFpEF, and HFrEF groups, respectively (p < 0.001). The 90-day all-cause mortality was 0.9%. Corresponding 90-day all-cause mortality rates were 0.04%, 4%, and 11%, respectively (p < 0.001). Independent positive predictors of HF events included HFrEF (aHR 19.400), HFpEF (adjusted hazard ratio [aHR] 8.632), heart transplant (aHR 7.485), hyperlipidemia (aHR 3.184), valvular heart disease (aHR 2.267), chronic kidney disease stage ≥ 3 (aHR 1.715), and ischemic heart disease (aHR 1.987). Protective factors included non-cardiac solid organ transplant (aHR 0.333). Conclusions: Bezlotoxumab appears safe in patients without HF history but is associated with a significantly increased risk of HF exacerbation in those with pre-existing HF, especially HFrEF.