Early rhythm control compared to rate control in atrial fibrillation – A systematic review, meta-analysis, and meta-regression

This meta-analysis aimed to compare the effectiveness of early rhythm control to rate control, and whether catheter ablation derived more benefit compared to other methods of rhythm control. A comprehensive literature search was conducted on PubMed, SCOPUS, and EuropePMC up to July 2, 2024. The primary outcome of this study was major adverse cardio-cerebrovascular events (MACCE), defined as a composite of mortality, stroke/systemic embolism, heart failure hospitalization (HFH), and acute coronary syndrome (ACS) during the follow-up period. Outcome measures were adjusted hazard ratios (aHR). A total of 504,124 patients from 11 studies were included in this systematic review and meta-analysis. Early rhythm control was significantly associated with reduction in MACCE (aHR 0.85 [95% CI 0.80, 0.90], p < 0.001; I 2 : 23%), stroke (aHR 0.79 [95% CI 0.72, 0.86], p < 0.001; I 2 : 25%), HFH (aHR 0.87 [95% CI 0.78, 0.96], p = 0.008; I 2 : 48%), and ACS (aHR 0.80 [95% CI 0.66, 0.96], p = 0.018; I 2 : 40%). No mortality benefit (aHR 0.93 [95% CI 0.85, 1.01], p = 0.066; I 2 : 67%) was observed; however, mortality benefit became evident (aHR 0.87 [95% CI 0.85, 0.89], p < 0.001) upon removal of a study during a leave-one-out sensitivity analysis. Meta-regression analysis showed that the benefits of early rhythm control in terms of MACCE were more pronounced with ablation (coefficient -0.004, p = 0.010, R 2 : 100%). Early rhythm control was associated with better outcomes compared to rate control in AF, with a more pronounced benefit observed for ablation.