Patent foramen ovale closure vs. medical therapy for recurrent stroke prevention: Evolution of treatment effect during follow-up.

BACKGROUND Little is known regarding changes in treatment effect over time associated with patent foramen ovale (PFO) closure among patients with embolic stroke of unknown origin. METHODS We reconstructed Kaplan-Meier curves for stroke from individual randomized trials comparing PFO closure vs. medical therapy among patients with embolic stroke. Random effects Cox-regression analyses were performed in order to estimate hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS A total of 2531 patients enrolled across 4 randomized trials were included. PFO closure was associated with a significant reduction in the risk of stroke at longest available follow-up (HR 0.18, 95%CI 0.06 to 0.59, P=0.005). However, recurrent stroke was already significantly reduced among patients randomized to PFO closure at 1-year (HR 0.40, 95%CI 0.20 to 0.80, P=0.010), with the treatment effect remaining consistent (P-for-interaction=0.356) between 1- and 5-year (HR 0.14, 95%CI 0.05 to 0.55, P=0.005) and beyond 5-year (HR 0.20, 95%CI 0.03 to 1.19, P=0.077). CONCLUSIONS Among patients with embolic stroke of unknown origin, PFO closure reduces the risk of stroke compared with medical therapy, with a significant reduction in recurrences starting already within 1-year after percutaneous PFO closure