Risk of Arrhythmia with Exposure to Anthracyclines: A Systematic Review, Meta-Analysis, and Network Meta-Analysis

Abstract

Objective Whether clinical application of anthracyclines is associated with increasing arrhythmic risk remains controversial. In order to evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each individual 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 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 for arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62–2.24) and 114% increase in the risk for supraventricular arrhythmia (OR 2.14; 95% CI 1.18–3.89). And the single-arm studies also indicated that incidence of arrhythmia rate is 20%, 95%CI is 15/100 − 25/100. Epirubicin ranked most likely to have the highest risk for 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 for arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability for arrhythmia. These results indicated cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and possible therapy for anthracyclines associated arrhythmia should be explored.

Anthracycline’s Effects on Heart Rate Variability in Children with Acute Lymphoblastic Leukemia: Early Toxicity Signs—Pilot Study

“…Doxorubicin has been shown to increase sympathetic activity shortly after administration, thus correlating with the increased acute pro-arrhythmogenic risk identified in some studies [12]. Life-threatening arrhythmias are, however, extremely rare, with most studies reporting an increase in supraventricular tachycardia incidence and a prolonged QT interval following treatment [13,44]. In our study, the number of supraventricular or ventricular extrasystoles occurring after the first anthracycline-including protocol (corresponding to half the total cumulative dose) was within the reference range for age.…”

“…Recently, tissue Doppler imaging (TDI) and global longitudinal strain (GLS) have emerged as great tools in detecting subclinical diastolic disfunction induced by chemotherapeutic agents [10,11]. Also, ECG monitoring is constantly needed, as arrhythmias and even acute life-threatening events have been reported to occur even from the beginning of the oncologic treatment [12,13]. What is more, recent studies have shown that cardiotoxicity can also present itself as an alteration in cardiac autonomic function, even shortly after treatment completion [14,15].…”