Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review & bayesian network meta-analysis. (July 2022)

• Record Type: Journal Article
• Authors: Sayed, Ahmed; Abdelfattah, Omar M.; Munir, Malak; Shazly, Omar; Awad, Ahmed K.; Ghaith, Hazem S.; Moustafa, Khaled; Gerew, Maria; Guha, Avirup; Barac, Ana; Fradley, Michael G.; Abela, George S.; Addison, Daniel
• Is Part Of: European journal of cancer. Volume 169(2022)
• Page Start: 82
• Page End: 92
• Publication Date: 2022-07
• Subjects: Malignancy -- Cardio-protection -- Cardio-oncology -- Heart failure -- Long-term outcomes; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.03.024
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: 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. Methods: 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). Results: 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%). Conclusion: 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. Graphical abstract: Image 1 Highlights: 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.