The Case for Selective Patent Foramen Ovale Closure After Cryptogenic Stroke

Abstract

Controversy has persisted for over a decade whether transcatheter patent foramen ovale (PFO) closure reduces the rate of recurrent ischemic stroke for patients who have had a cryptogenic ischemic stroke and have a PFO. In September 2017, 3 positive randomized trials: RESPECT long-term (Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment trial), REDUCE (GORE® HELEX® Septal Occluder / GORE® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging-Confirmed TIA in Patients With Patent Foramen Ovale [PFO]), and CLOSE (Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence) were published. All 3 trials studied young to middle age patients with cryptogenic ischemic strokes found to have a PFO, and compared recurrent stroke rates after PFO closure versus medical therapy alone. All trials had primary end points of recurrent ischemic strokes, a superiority design, and reported results in the intention to treat population. The long-term results of the RESPECT trial led to the Food and Drug Administration approval of the AMPLATZER PFO Occluder for a secondary prevention indication. There was a 45% risk reduction in the device arm for recurrent ischemic stroke with an event rate of 0.58 versus 1.07 per 100 patient-years (hazard ratio, 0.55; 95% confidence interval, 0.305–0.999; log-rank P =0.046). The primary efficacy result of the REDUCE trial utilizing the HELEX and CARDIOFORM devices demonstrated a risk reduction of 77% (hazard ratio, 0.23; 95% confidence interval, 0.09–0.62; log-rank P =0.001). In the CLOSE trial, device closure plus long-term antiplatelet therapy versus antiplatelet therapy alone demonstrated a risk reduction of 97% (hazard ratio, 0.03; 95% confidence interval, 0–0.25; log-rank P <0.001). Each trial demonstrated a low frequency of device- and procedure-related complications, including a slight increase in the rate of paroxysmal atrial fibrillation in the device arm. This review focuses on summarizing the trial results and translating the results and methods from investigative trials into clinical practice.