Early rhythm control in patients with atrial fibrillation and cancer: a subgroup analysis of the EAST-AFNET 4 trial

Background Early rhythm control improves cardiovascular outcomes in atrial fibrillation (AF) patients at risk, but its benefits in patients with cancer remain unclear. Objectives This study aimed to evaluate the effectiveness and safety of early rhythm control in patients with AF and history of cancer. Methods This secondary analysis of EAST-AFNET 4 compared patients with and without a history of cancer. The analysis included the primary outcome, a composite of cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome; the safety outcome, a composite of all-cause death, stroke, and prespecified serious adverse events of special interest related to rhythm-control therapy; and rhythm at 24 months. Results Cancer history was available in 2779/2789 patients (99.6%). Cancer history was present in 216/2779 (7.8%, mean age 73 years, 95 (44%) women, mean CHA2DS2-VASc score 3.5). There was no evidence of heterogeneity for the efficacy outcome of the trial (pinteraction=0.232). Rates of sinus rhythm at 24 months were not different (cancer: 84.9%, without cancer 81.8%; pinteraction=0.601). In patients with a cancer history, the safety outcome occurred more often with early rhythm control than with usual care, with more strokes and more adverse events of rhythm control therapy. Conclusion These hypothesis-generating data suggest that early rhythm control therapy is effective in patients with a cancer history and atrial fibrillation but may be less safe than in patients without a cancer history. More research is needed to understand the mechanisms of stroke and the safety of rhythm control in patients with a history of cancer.