Survivors of Childhood Cancer With High Anthracycline Exposure: Can a Beta-Blocker Improve Cardiac Function?

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In a U.S./Canadian phase IIb trial (PREVENT-HF) reported in The Lancet Oncology, Armenian et al found that the beta-blocker carvedilol did not significantly improve cardiac function—measured as standardized left ventricular wall thickness–dimension ratio Z score (LVWT/Dz)—vs placebo in survivors of childhood cancer with high levels of exposure to anthracyclines.

As stated by the investigators, “Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure.”  

Study Details

In the multicenter double-blind trial, 182 eligible patients with any cancer diagnosis resulting in cumulative anthracycline exposure of at least 250 mg/m² by age 21 years were randomly assigned between July 2012 and June 2020 to receive oral carvedilol up-titrated from 3.125 mg per day to 12.5 mg per day (n = 89) or placebo (n = 93) for 2 years. Patients had completed cancer treatment at least 2 years previously, and had an ejection fraction of at least 50%, fractional shortening of at least 25%, or both.

The primary outcome measure of the trial was to determine the effect of carvedilol on standardized LVWT/Dz. Outcomes were assessed in the modified intention-to-treat (ITT) population (all randomly assigned patients with a baseline and at least one subsequent echocardiogram measurement), consisting of 75 patients in the carvedilol group and 76 in the placebo group.

Key Findings

Patients had a median age of 24.7 years (interquartile range [IQR] = 19.6–36.6 years), 50% were female, and 65% were White. At data cutoff in June 2022, median follow-up was 725 days (IQR = 378–730 days). In the modified ITT population, LVWT/Dz was −0.14 (95% confidence interval [CI] = −0.43 to 0.16) in the carvedilol group vs −0.45 (95% CI = −0.77 to −0.13) in the placebo group (difference = 0.31, 95% CI = –0.10 to 0.73, P = .14).

Among all randomly assigned patients, grade 2 adverse events were observed in two patients (2%) in the carvedilol group (shortness of breath and arthralgia in one patient each) and no patients in the placebo group. No adverse events of grade ≥ 3 were observed, and no deaths were reported.

The investigators concluded, “Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors.”

Saro H. Armenian, DO, of the Department of Pediatrics and Department of Population Sciences, City of Hope Comprehensive Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Cancer Institute, Leukemia & Lymphoma Society, St. Baldrick’s Foundation, and others. For full disclosures of the study authors, visit

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