Patent foramen ovale closure versus medical therapy for prevention of recurrent cryptogenic embolism: updated meta-analysis of randomized clinical trials

Clin Res Cardiol. 2018 Sep;107(9):788-798. doi: 10.1007/s00392-018-1246-y. Epub 2018 Apr 11.

Abstract

Background: We performed an updated meta-analysis of all randomized-controlled trials (RCTs) comparing patent foramen ovale (PFO) closure with medical therapy for prevention of recurrent ischemic stroke.

Methods and results: We searched Medline, EMBASE, and Cochrane databases, and proceedings of international meetings for RCTs of patients with cryptogenic stroke and PFO comparing percutaneous PFO closure versus medical therapy for prevention of recurrent ischemic stroke. The primary outcome was a composite ischemic/embolic endpoint comprising stroke, transient ischemic attack (TIA), peripheral embolism, and early death in the intention-to-treat population. Secondary outcomes were all-cause death, stroke, TIA, atrial fibrillation (AF), and major bleeding. Of 3440 enrolled patients across five RCTs, 1829 were allocated to PFO closure and 1611 to medical therapy. The follow-up ranged from 2 to 5.9 years. PFO closure reduced the risk of the composite outcome [HR 0.52, (0.36-0.77); p < 0.01], and stroke, [HR 0.39, (0.19-0.83); p < 0.01], and increased the risk of AF [OR 3.75, (2.44-5.78); p < 0.01] as compared to medical therapy. NNT for stroke was 37 and NNH for AF 49, indicating a net clinical benefit of PFO closure. The meta-analysis had 95% power to detect a 50% relative risk reduction (RRR) in the primary outcome and 89% power to detect a 70% RRR in ischemic stroke. The risk of all-cause death (HR 1.08, p = 0.90), TIA [HR 0.73, (0.49-1.09); p = 0.12], and major bleeding [OR 0.97, (0.44-2.17); p = 0.95] was comparable between the groups.

Conclusions: Among patients with cryptogenic stroke and PFO, percutaneous closure of PFO is superior to medical therapy in preventing recurrent ischemic/embolic events and stroke but is associated with an increased risk of AF.

Keywords: Persistent foramen ovale; Stroke; Structural intervention; Transcatheter intervention.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Fibrinolytic Agents / therapeutic use*
  • Foramen Ovale, Patent / surgery*
  • Global Health
  • Humans
  • Incidence
  • Postoperative Complications*
  • Randomized Controlled Trials as Topic / methods*
  • Recurrence
  • Risk Factors
  • Septal Occluder Device / adverse effects*
  • Stroke* / epidemiology
  • Stroke* / etiology
  • Stroke* / prevention & control
  • Thrombolytic Therapy / methods*

Substances

  • Fibrinolytic Agents