No Benefit With Carvedilol for Childhood Cancer Survivors at Risk for HF

Low-dose carvedilol was not associated with improved left ventricular wall thickness-dimension ratio Z score (LVWT/Dz) in long-term childhood cancer survivors at risk for heart failure (HF). These findings were published in The Lancet Oncology.

Exposure to high-dose anthracycline during treatment for cancer increases risk for HF. Carvedilol is associated with improved cardiac function in the setting of HF but has not been tested as a cardioprotective therapy.

The PREVENT-HF study (ClinicalTrials.gov Identifier: NCT02717507) was a randomized, double-blind, phase 2b trial conducted at 30 sites in the United States and Canada between 2012 and 2020. 

Patients (N=182) who survived childhood cancer and had at least 250 mg/m² cumulative exposure to anthracycline before age 21 years were randomly assigned in a 1:1 ratio to receive 3.125 mg up-titrated to 12.5 mg daily carvedilol (n=89) or placebo (n=93) for 2 years. 

The primary endpoint was the change in LVWT/Dz.

The carvedilol and placebo cohorts comprised 52% and 48% men, median age 23.2 and 25.2 years, and cancer diagnosed at 11.0 and 11.7 years old, respectively. The most common cancer diagnoses were acute myeloid leukemia, osteosarcoma, acute lymphoblastic leukemia, and Ewing sarcoma.

At baseline, the mean LVWT/Dz was −0.14 (SD, 1.47) among the carvedilol group and −0.09 (SD, 1.66) in the placebo group. 

Of the 114 participants who completed the study at 2 years (59 [39%] in carvedilol group and 55 [36%] in placebo group), no significant difference in LVWT/Dz was observed between groups (mean difference [MD], 0.31; 95% CI, −0.10 to 0.73; P =.14).

However, the investigators noted a significant treatment group-by-time since cancer diagnosis interaction (β, 0.032; 95% CI, 0.015-0.051; P =.0004).

This study was limited by not recruiting the desired initial sample size of 250 participants.

“Although no difference was found for the primary endpoint, treatment effects varied by time since diagnosis, suggesting greater activity of carvedilol among longer-term survivors,” the study authors concluded.