The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown.

We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure. Data were analyzed using a Bayesian network meta-analysis with random effects.

A total of 16 trials reported cardiotoxicity as a dichotomous outcome among 1918 patients, evaluating dexrazoxane, angiotensin antagonists, beta-blockers, combination angiotensin antagonists and beta-blockers, statins, Co-enzyme Q-10, prenylamine, and N-acetylcysteine. Compared with control, dexrazoxane reduced cardiotoxicity with a pooled odds ratio (OR) of 0.26 (95% credible interval [CrI] 0.11–0.74) and had the highest probability (33%) of being most effective. No other agent was demonstrably better than placebo. Angiotensin antagonists had an 84% probability of being most effective in a sensitivity analysis excluding one outlying study (OR 0.06 [95% CrI 0.01– 0.24]). When the outcome was restricted to heart failure, dexrazoxane was associated with an OR of 0.12 (95% CrI 0.06–0.23) relative to control and had 58% probability of being most effective, while angiotensin antagonists had an OR of 0.18 (95% CrI 0.05–0.55). Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death.

Moderate quality data suggest that dexrazoxane, and low quality data suggest angiotensin antagonists, are likely to be effective for cardiotoxicity prevention.