Net clinical benefit of PFO closure versus medical treatment in patients with cryptogenic stroke: A systematic review and meta-analysis.

Abstract

The ideal treatment for patent foramen ovale (PFO) in patients with cryptogenic stroke remains controversial and is being evaluated. The objective of this study was to evaluate the net clinical benefit (NCB) between PFO closure and medical treatment. We searched three electronic databases from inception until January 2022. The primary outcomes were the NCB-1, defined as the cumulative incidence of stroke, major bleeding, atrial fibrillation/flutter, and serious procedural or device complications; the NCB-2 and NCB-3 were defined as NCB1 but using a weighted factor of 0.5 and 0.25 for atrial fibrillation/flutter events, respectively. We also evaluated each component outcome of NCB as a secondary outcome. Risk ratios (RR) and 95% confidence intervals (CI) of each outcome were calculated (random-effects model). Our analysis included six RCTs (n=3750 patients). The rates of NCB-1, NCB-2, and NCB-3 were not different between PFO closure and medical treatment. The heterogeneity between trials was low to moderate. Stroke showed a significant relative decrease of 44% (95% CI, 21-60%), favoring the PFO closure arm. Atrial fibrillation/flutter increased by 4.04 times (95% CI, 1.57-8.89) in the PFO closure compared with the medical treatment group. In a meta-regression analysis, the reduction in NCB-1 with PFO closure increased as the proportion of patients treated with the Amplatzer device increased (p=0.02), and the reduction in NCB-1, NCB-2, and NCB-3 with PFO closure increased as the proportion of patients treated with substantial PFO size increased (p=0.03). The NCB between PFO closure and medical treatment was not different, suggesting individualized treatment to maximize benefit.