Konstantinos Pamporis, Dimitrios Tsiachris, C K Antoniou, Serge Boveda, A Kordalis, Konstantinos Vlachos, Pierre Jaïs, Paschalis Karakasis, Michail Botis, Panagiotis Theofilis, Aikaterini-Eleftheria Karanikola, Konstantinos Tsioufis
BACKGROUND: Several randomized controlled trials (RCTs) have examined catheter ablation (CA) and class III antiarrhythmic drugs (AAD) in secondary prevention of ventricular arrhythmias (VA) in patients with ischemic cardiomyopathy (ICM) and an implantable cardioverter-defibrillator (ICD). This study sought to evaluate the efficacy and safety of CA versus AADs (amiodarone, sotalol) in this population. METHODS: MEDLINE (Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until October 26, 2025 for RCTs. Double-independent study selection, data extraction and quality assessment were performed. Appropriate shock and electrical storm (ES) were the primary efficacy outcomes. Risk ratios (RR) with 95% confidence intervals (CI) were calculated via random-effects frequentist models. Registered in PROSPERO: CRD42025640326. RESULTS: Totally, 14 RCTs (13 in main analysis) and 2,237 patients (2,177 in main analysis) were analyzed. CA was superior against AAD in appropriate shocks (RR = 0.68, 95%CI = [0.47,0.99]; p = 0.043). A nonsignificant reduction was found in ES (RR = 0.81, 95%CI = [0.63,1.03]; p = 0.088) and VA recurrence (RR = 0.86, 95%CI = [0.68,1.08]; p = 0.197). CA was superior to AAD in heart failure (HF) exacerbation (RR = 0.76, 95%CI = [0.58,0.99], p = 0.043) and undetected ventricular tachycardia (VT) (RR = 0.27, 95%CI = [0.15,0.46], p < 0.001). No differences were noted regarding any serious adverse event, all-cause or cardiovascular mortality and cardiovascular or VA hospitalization. In secondary analyses, CA was superior against amiodarone in serious adverse events (RR = 0.33, 95%CI = [0.15,0.75]). The results remained robust in sensitivity analyses. CONCLUSIONS: CA was superior in efficacy with comparable safety compared to AAD in reducing appropriate shocks, HF and undetected VT in patients with ICM and an ICD for secondary prevention. No significant differences were found in overall VA recurrences, ES, all-cause or cardiovascular mortality.