Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis

Ann Oncol. 2017 Mar 1;28(3):628-633. doi: 10.1093/annonc/mdw671.

Abstract

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

Methods: 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.

Results: 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.

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

Keywords: Bayesian; anthracycline; cardiotoxicity; heart failure; meta-analysis; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Acetylcysteine / therapeutic use
  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensins / antagonists & inhibitors
  • Anthracyclines / adverse effects*
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / mortality
  • Cardiomyopathies / pathology
  • Clinical Trials as Topic
  • Dexrazoxane / therapeutic use
  • Heart Failure / chemically induced
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / pathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Network Meta-Analysis
  • Prenylamine / therapeutic use
  • Ventricular Dysfunction, Left / chemically induced
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / mortality
  • Ventricular Dysfunction, Left / pathology

Substances

  • Adrenergic beta-Antagonists
  • Angiotensins
  • Anthracyclines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Dexrazoxane
  • Prenylamine
  • Acetylcysteine