- •LVEF preservation was ∼4% higher in the cardioprotective group
- •Therapy for ≥1 year was most effective: number needed to treat 21 to prevent one HF.
- •Empiric cardioprotective therapy reduces incident heart failure (HF) by nearly 70%.
- •Aldosterone antagonists were most effective in preserving LVEF
- •Dexrazoxane was most effective in preventing new onset cardiotoxic HF.
Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown.
Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI).
Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19–0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81–5.07), increased hypotension (RR:3.27; 95% CrI:1.38–9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for ‘any’ cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%).
Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.
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Published online: May 04, 2022
Accepted: March 11, 2022
Received: February 9, 2022
© 2022 Elsevier Ltd. All rights reserved.
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- Reply to comment on “Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review and Bayesian network meta-analysis”European Journal of CancerVol. 174
- PreviewWe would like to thank Dr. Rizzo and Dr. Brandi for their constructive comments on our study. We concur with their statement on the importance of conducting head-to-head clinical trials that are sufficiently powered for the detection of clinically meaningful outcomes. We agree that although our analysis showed a meaningful benefit to cardioprotective therapies, it is not a substitute for such large prospective trials.
- Letter re: “Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review and Bayesian network meta-analysis”European Journal of CancerVol. 174
- PreviewThe cardiotoxicity of anticancer drugs represents a long-standing, important, and widely discussed issue in medical oncology . We have witnessed impressive advances in cancer management over the last decade, with novel treatments reporting unprecedented response rates and improving clinical outcomes in several haematological and solid tumours . Nonetheless, if on the one hand, new therapies have showed superior efficacy; on the other hand, these treatments have been associated with a non-negligible risk of increased cardiac toxicities.