Introduction: The RESPECT trial evaluated the superiority of patent foramen ovale (PFO) closure over standard-of-care medical management (MM) in patients with PFO and cryptogenic stroke (CS).
Hypothesis: Analysis of stroke mechanisms and topography of recurrent events will provide insight into the clinical efficacy of PFO closure.
Methods: RESPECT is a prospective, multicenter, randomized event-driven trial of PFO closure vs. MM in patients with CS and PFO. Patients were randomized to treatment in a 1:1 ratio. The primary results were analyzed and reported when the target of 25 events were adjudicated (NEJM 2013; 368:1092-100). At that time, mean follow-up was 2.6 years, range 0-8.1 years. Prospective follow-up has continued. Recurrent strokes were assigned phenotypes using the ASCOD system by investigators blinded to treatment assignment.
Results: 980 subjects were randomized to PFO closure (n=499) or MM (n=481). The primary analysis in the intention-to-treat population after a mean follow-up of 2.6 years exhibited a hazard ratio of 0.49 favoring closure that did not reach statistical significance (p=0.08). The per-protocol cohort demonstrated a significant reduction in the primary endpoint in favor of closure (HR 0.37, p=0.03). Among the initial 25 recurrent ischemic strokes, MM patients more often had superficial or multiple-penetrator territory infarcts (12 vs 4) and infarcts of larger size (69% vs 14%, p=0.06). Since the primary results report, follow-up has continued for an additional 3.5 years and additional recurrent infarcts have been observed. Long-term stroke rates, phenotyping, and topography will be presented.
Conclusions: Our prior reports suggest that PFO closure was associated with prevention of stroke subtypes particularly associated with PFO, including superficial and larger infarcts. Long-term safety, efficacy, and stroke mechanisms, with >4000 patient-years of follow-up will be presented.