Cardiac Arrhythmia Risk after Anti-Cancer Drug Exposure and Related Disease Molecular Imaging Outlook: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.

Simple Summary: Anthracyclines have a central role in anti-cancer therapy, but their side effects of chemotherapy-induced cardiotoxicity (AIC) during systemic administration have always been a problem for both patients and clinicians. The application of anthracycline agents leads to arrhythmias, causing nonspecific ECG changes. And the incidence rates of abnormal QT changes could be early markers of AIC. Therefore, we conducted a systematic review, meta-analysis, and network meta-analysis to evaluate the arrhythmic risk of anthracyclines and the comparative risk for each agent. We included 4 cohort studies, 8 RCTs, and 18 single-arm studies, and the result shows anthracyclines were associated with a statistically significant 90% increase in the risk of arrhythmia and a 114% increase in the risk of supraventricular arrhythmia. Among them, epirubicin ranked the most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis. The purpose of this research is to improve the monitoring of ECGs by clinicians while applying anthracyclines and to try to use molecular imaging technology to study the mechanism of drug action on cardiac electrophysiology in the future. The effects of anthracycline agents on the electrophysiological properties of cardiac cells can be better understood with the help of imaging molecular targets in cardiac cells, which may result in safer and more effective clinical use of the drugs. Background: Chemotherapy is the main first-line treatment, but there is a problem of adverse reactions to systemic drugs. Chemotherapeutic agents may cause adverse effects on the body, influencing the prognosis. Whether the clinical application of anthracyclines is associated with an increased arrhythmic risk remains controversial. To evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each drug, we conducted a systematic review, meta-analysis, and network meta-analysis. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case–control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. Results: In total, 4 cohort studies, 8 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines' use was associated with a statistically significant 90% increase in the risk of arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62–2.24) and a 114% increase in the risk of supraventricular arrhythmia (OR 2.14; 95% CI 1.18–3.89). And the single-arm studies also indicated that the incidence of arrhythmia rate is 20% and the 95% CI is 15/100–25/100. Epirubicin ranked most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80–2105.83]) by network meta-analysis. Conclusions: Our findings show a significant association between anthracyclines' use and an increased risk of arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability of arrhythmia. These results indicated that cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and a possible therapy for anthracycline-associated arrhythmia should be explored. Molecular imaging technology is an important means to study the mechanism of drug action on cardiac electrophysiology in the future. By imaging molecular targets in cardiac cells, the effects of drugs on the electrophysiological properties of cardiac cells can be understood, which provides information for the development of safer and more effective drugs. [ABSTRACT FROM AUTHOR]