Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses

Prostate Cancer Prostatic Dis. 2021 Mar;24(1):244-252. doi: 10.1038/s41391-020-00275-3. Epub 2020 Aug 28.

Abstract

Background: Abiraterone and enzalutamide may increase the risk of cardiovascular events in patients with castration-resistant prostate cancer (CRPC).

Methods: A comprehensive literature search was performed using a combination of keywords related to "abiraterone," "enzalutamide," "prostate cancer," and "adverse events." Phase II-IV randomized controlled trials (RCTs) on abiraterone or enzalutamide for patients with nonmetastatic or metastatic CRPC were included. Outcome measures included (1) any grade cardiac disorder, (2) severe grade cardiac disorder, (3) any grade hypertension, and (4) severe grade hypertension, as defined by the Common Terminology Criteria for Adverse Events. Pairwise meta-analysis and Bayesian network meta-analyses were performed to investigate the risk ratios (RRs) of abiraterone and enzalutamide. Surface under cumulative ranking curves (SUCRAs) and cumulative ranking probability plots based on the probability of developing cardiac disorders or hypertension were presented.

Results: A total of 7103 patients from seven RCTs were included. Upon pairwise meta-analysis, abiraterone was associated with increased risks of any grade (RR = 1.34, 95% confidence interval (CI) = 1.05-1.73) and severe grade cardiac disorders (RR = 1.71, 95% CI = 1.16-2.53); enzalutamide was associated with increased risks of any grade (RR = 2.66, 95% CI = 1.93-3.66) and severe grade hypertension (RR = 2.79, 95% CI = 1.86-4.18). Based on the SUCRA rankings, abiraterone had a higher probability of cardiac disorders (84.84% for any grade and 85.12% for severe grade) than enzalutamide (62.83% for any grade and 50.76% for severe grade); whereas enzalutamide had a higher probability of hypertension (99.43% for any grade and 89.71% for severe grade) than abiraterone (49.08% for any grade and 49.37% for severe grade).

Conclusions: Abiraterone and enzalutamide had different adverse effects on the cardiovascular system. We should take this into consideration when we are deciding on the choice of novel hormonal agents for patients with CRPC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Androstenes / adverse effects*
  • Androstenes / therapeutic use
  • Benzamides / adverse effects*
  • Benzamides / therapeutic use
  • Cardiovascular System / drug effects*
  • Humans
  • Male
  • Network Meta-Analysis
  • Nitriles / adverse effects*
  • Nitriles / therapeutic use
  • Phenylthiohydantoin / adverse effects*
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*

Substances

  • Androstenes
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • enzalutamide
  • abiraterone