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BackgroundAtrial fibrillation (AF) and heart failure (HF) often coexist. The treatment of AF in patients with HF has been challenging because of the ongoing debate about the merits of catheter ablation vs. drug therapy.MethodsThe Cochrane Library, PubMed, and www.clinicaltrials.gov were searched until June 14, 2022. Inclusion criteria were catheter ablation compared with drug therapy in adults with AF and HF in randomized controlled trials (RCTs). Primary outcomes consisted of all-cause mortality, re-hospitalization, change in left ventricular ejection fraction (LVEF), and AF recurrence. Secondary outcomes referred to quality of life [QoL; measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ)], six-minute walk distance (6MWD), and adverse events. The PROSPERO registration ID was CRD42022344208.FindingsIn total, nine RCTs with 2,100 patients met the inclusion criteria, with 1,062 for catheter ablation and 1,038 for medication. According to the meta-analysis, catheter ablation significantly reduced all-cause mortality compared with drug therapy [9.2% vs. 14.1%, OR: 0.62, (95% CI: 0.47–0.82), P = 0.0007, I2 = 0%], improved LVEF [MD: 5.65%, (95% CI: 3.32–7.98), P |