Cardiovascular Events in Patients With Acute Myeloid Leukemia Treated With Venetoclax: A Multicenter Cohort Study

Patients with acute myeloid leukemia (AML) treated with hypomethylating agents and venetoclax (HMA-VEN) may be at risk for cardiovascular complications. The incidence, associations, and prognostic implications of these events remain poorly defined.

The purpose of this study was to evaluate the incidence, risk factors, and prognostic significance of major adverse cardiovascular events (MACE) in AML patients treated with HMA-VEN and to identify clinical and genetic predictors.

We conducted a multicenter retrospective cohort study across 6 U.S. health care systems between January 2017 and July 2024. The study included 1,012 adults (mean age 69 ± 12.5 years; 57% male) with newly diagnosed or relapsed/refractory AML treated with HMA-VEN. The primary outcome was MACE, defined as atrial fibrillation, heart failure, left ventricular ejection fraction reduction, stroke/transient ischemic attack, acute coronary syndrome, angina, ventricular tachycardia/fibrillation, myocarditis, or cardiovascular death. The secondary outcome was noncardiac mortality. Variables associated with MACE and mortality were analyzed using Fine-Gray competing risk and Cox proportional hazards models.

MACE occurred in 20% of patients (n = 200), with a median time to first MACE of 120 days and a 12-month cumulative incidence of 17%. Atrial fibrillation (6%), stroke/transient ischemic attack (5%), left ventricular ejection fraction reduction (5%), and heart failure (4%) were most frequent. Diabetes independently predicted MACE (subdistribution HR: 1.4; 95% CI: 1.03-1.89; P = 0.031). In the matched cohort, MACE was associated with increased mortality (73% vs 56%; HR: 1.96; 95% CI: 1.59-2.42; P < 0.001).

MACE are frequent and occur early in patients with AML treated with HMA-VEN, particularly in patients with diabetes, and are associated with lower survival.