Natural Progression of Left Ventricular Function following Anthracyclines without Cardioprotective Therapy: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Anthracyclines form the backbone of many systemic chemotherapy regimens with great response rates for cancers. Yet, their established dose-limiting cardiotoxic effects can also lead to a reduction in cardiac function and an increased risk of heart failure. This PRISMA-adherent systematic review and meta-analysis of randomised-controlled trials aims to evaluate the progression of cardiac dysfunction and levels of natriuretic peptides, and risk of heart failure in cancer patients receiving anthracyclines. Our review included cohorts which followed patients over two years from the administration of anthracyclines and demonstrated that there were no significant declines compared to after six months. This period would be the most crucial for concurrent cardioprotection to prevent adverse remodelling. We also found the risk of developing significant declines in LVEF occurred in approximately one in six. The confounding effect of receiving concomitant trastuzumab and baseline LVEF was also negligible. ABSTRACT: Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about. Methods: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.