Standardized mortality ratio and long-term stroke recurrence after PFO-closure

Background Closure of a persistent foramen ovale (PFO) is recommended in cryptogenic stroke to prevent recurrence of stroke. The long-term outcome regarding recurrent strokes and mortality outside clinical trials is however largely unknown. Objectives This study investigates standardized mortality ratio (SMR), recurrent ischemic stroke and factors associated with recurrence, in patients with a previous closure of a PFO. Methods Data from national registers on congenital heart disease and stroke were crossmatched to identify patients who had undergone a PFO-closure due to ischemic stroke between 2001 and 2018. SMR, i.e the ratio between observed and expected deaths, was analyzed and stroke recurrence was assessed. Cox regression analysis was applied to study factors possibly associated recurrence of ischemic stroke. Results A total of 827 patients (60.5% men) with a median age of 47.9 (IQR 40.0-55.6) years at PFO-closure were identified and observed over a median time of 8.0 years (IQR 4.8-11.0). During follow up, 23 patients died. SMR was 0.65 (95% confidence interval [CI] 0.41-0.98). Thirty-four ischemic strokes occurred, and the incidence was 0.51 ischemic strokes per 100 patients and year. The cumulative incidence was 0.5% at one year, 1.1% at two years, 2.9% at five years and 4.6% at ten years. Out of 34 patients who suffered a recurrent stroke, 27 were on antithrombotic therapy at time of stroke (22 on antiplatelets, 3 on anticoagulants and 2 on both antiplatelet and anticoagulant therapy). New onset atrial fibrillation after PFO-closure (Hazard ratio [HR] 8.5, 95% CI 3.0-24.6) and active or previous smoking (HR 2.5, 95%CI 1.3-5.0) were associated with recurrence of ischemic stroke whereas age, sex and other cardiovascular risk factors were not. Conclusions In this real-world study, treated patients have a lower mortality than a matched population. Stroke recurrence is in line with previous clinical trials. New onset atrial fibrillation after PFO-closure and active or previous smoking are potential possible targets for prevention of recurrent stroke