Long-Term Outcomes of PFO Closure Versus Medical Therapy after Stroke Compared in RESPECT Trial
September 19, 2017—In The New England Journal of Medicine (NEJM), Jeffrey L. Saver, MD, et al published findings from the RESPECT trial that investigated long-term outcomes of patent foramen ovale (PFO) closure or medical therapy after stroke (2017;377:1022–1032). The investigators concluded that among adults who had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up.
The findings from RESPECT were presented in November 2016 as a First Report Investigation at TCT 2016, the 28th annual Transcatheter Cardiovascular Therapeutics scientific symposium in Washington, DC. RESPECT evaluated the Amplatzer PFO occluder device (St. Jude Medical, Inc., now Abbott Vascular). The company sponsored the trial.
As summarized in NEJM, RESPECT is a multicenter, randomized, open-label trial, with blinded adjudication of endpoint events. The investigators randomly assigned patients aged 18 to 60 years who had a PFO and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group).
The primary efficacy endpoint was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously (NEJM; 2013;368:1092-1100); the current analysis of data from the extended follow-up period was considered to be exploratory, noted the investigators.
The RESPECT investigators enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3,141 patient-years in the PFO closure group vs 2,669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group.
The investigators reported that in the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs medical therapy, 0.55; 95% confidence interval, 0.31 to 0.999; P = .046 by the log-rank test).
Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% confidence interval, 0.18 to 0.79; P = .007). Venous thromboembolism (including events of pulmonary embolism and deep vein thrombosis) was more common in the PFO closure group than in the medical-therapy group, reported the investigators in NEJM.