Treatment Options for Recurrent Thromboembolism in Patients With Cryptogenic Cerebrovascular Events: Medical Therapy Versus Device Closure or Surgical Repair of Patent Foramen Ovale

Abstract Patent foramen ovale (PFO) is a cardiac anatomic structure frequently found in the general population, with an estimated prevalence of 25%–30%. PFO has been linked to increased risk for thromboembolism, including ischemic systemic and cerebrovascular events. The risk stems from the potential of paradoxical embolization of thrombi originating from the venous system through the anatomic patency onto the left-heart circulation. In fact, PFO has been found in up to 40%–50% of adult patients with stroke of unknown origin (cryptogenic) using transesophageal echocardiography and serves as an independent predictor of cryptogenic stroke. To decrease the risk of recurrent cerebrovascular events in this population, multiple treatment strategies, including medical therapy, device closure, and surgical repair, have been initiated and studied. Although data on the medical management of cryptogenic stroke in the setting of PFO are limited, the available evidence supports the notion that both aspirin (81–325 mg/day) and warfarin (international normalized ratio goal 2–3) decrease the risk of recurrent cryptogenic stroke in patients with PFO, with the latter potentially achieving lower recurrence rates. However, the preferred therapy, the ideal antiplatelet dosing, the duration of therapy, and the benefit of newer antiplatelet agents (P2Y12 inhibitors) are still unknown. Current guidelines denote that there is insufficient evidence to establish whether anticoagulation is superior or equivalent to aspirin. Nevertheless, the guidelines recommend at least antiplatelet therapy for patients with PFO and prior ischemic cerebrovascular events. A large body of literature supports the application of percutaneous devices for closure of PFO, as it decreases the incidence of recurrent stroke in patients with cryptogenic stroke. Two PFO closure devices, the Amplatzer PFO occluder and the GORE Cardioform, have shown a 45% and 76% risk reduction, respectively, in randomized controlled trials, compared with medical therapy alone. The Amplatzer PFO occluder is already US Food and Drug Administration approved for this indication (since 2016) and the GORE Cardioform closure device is expected to receive approval by the end of 2017. Accordingly, the guidelines stand to change in the near future to include PFO device closure in addition to standard medical therapy for the management of patients with cryptogenic stroke. Surgical closure of PFO appears to be a safe approach; nevertheless, conflicting data exist regarding the efficacy of elimination of an interatrial shunt, and a valid concern for recurrent cerebrovascular events remains. As no direct comparison is currently available between the three main management approaches, there are no clear advantages of surgery over medical therapy or over percutaneous device closure. Accordingly, a surgical approach should be considered as the last therapeutic option, limited to select patients who sustained cryptogenic stroke with a high risk of recurrent events in whom both device closure and medical therapy have failed or are contraindicated.