Aspirin or anticoagulation after cryptogenic stroke with patent foramen ovale: systematic review and meta-analysis of randomized controlled trials

Introduction Since closure has restrictive eligibility criteria, the vast majority of patients with cryptogenic stroke and patent foramen ovale (PFO) receive medical treatment. However, the optimal antithrombotic strategy is still unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to define risk/benefit profile of anticoagulation compared with antiplatelet treatment in PFO-related stroke. Methods Systematic review protocol was registered in PROSPERO (CRD42019117559). Following PRISMA guidelines, we searched MEDLINE, EMBASE, and Cochrane CENTRAL database (2000-2019) for RCTs randomly allocating patients with cryptogenic stroke and PFO to medical treatment. Risk of bias was assessed with Cochrane RoB tool. Main outcomes were stroke recurrence and major bleeding. RoPE score-dependent analysis was implemented to define a possible role for patient selection. Results Five RCTs met inclusion criteria (3 high-, 1 fair-, 1 poor-quality RCTs). Overall, meta-analysis included 1565 patients (mean age 55.5 years), 753 (48.1%) receiving anticoagulation. Compared with antiplatelet treatment, anticoagulation conveyed no net benefit in prevention of recurrent stroke (OR = 0.66, 95% CI 0.41-1.07, p(heterogeneity) = 0.46), and associated with a non-significant higher risk of major bleeding (OR = 1.64, 95% CI 0.79-3.43, p(heterogeneity) = 0.57). In patients with high RoPE score, anticoagulation significantly reduced the risk of recurrent stroke (OR = 0.22, 95% CI 0.06-0.8, p(heterogeneity) = 0.88). Conclusion Our meta-analysis shows that anticoagulation confers no net benefit in recurrent stroke prevention over antiplatelets in patients with PFO-related stroke. RoPE score might help in selecting patients benefiting from anticoagulation, but further trials are needed to delineate risk/benefit profile of anticoagulation.