Two Trials Examine Device-Based PFO Closure

MIAMI BEACH, FLA.—Results from two randomized trials presented at TCT 2012—RESPECT and PC—address patent foramen ovale (PFO) closure for secondary stroke prevention in patients with cryptogenic embolism, showing some positive results with device therapy but by no means providing a final answer for this clinical area.

John D. Carroll, MD, of the University of Colorado Denver, Aurora, presented data on 980 patients (mean age, 46 years) diagnosed with cryptogenic stroke and PFO randomized to closure with the Amplatzer PFO Occluder (St. Jude Medical; n=499) or medical therapy within 270 days of the stroke. The device is made of wire mesh and is inserted percutaneously into the orifice.

Two-year event rates for stroke were low in both the device and medical therapy groups (1.6% vs. 3%).

The clinical risk reduction of stroke using the device ranged from 46.6% to 72.7% compared with medical therapy alone, depending on the analysis population being assessed. Among the intent-to-treat population, this reduction achieved borderline significance. In per-protocol and as-treated analyses, the reductions were statistically significant (see Figure).

PFO closure with the device exposed patients to very low risk for device- or procedure-related complications, Carroll said. Serious adverse events were similar between the device and medical therapy groups (23% vs. 21.6%). The total incidence of atrial fibrillation was not different between the device and medical therapy groups (3% vs. 1.5%; P=1). Researchers observed no device-related thrombus, erosion or embolization and no study-related deaths.

“Follow-up of patients is ongoing and will continue to provide additional longer-term information regarding benefits, risks and differential treatment effects in subpopulations,” Carroll said at the late-breaking trial session.

In the trial, medical therapy included one of four regimens: clopidogrel; warfarin; aspirin; aspirin plus dipyridamole. Forty-nine percent of patients had a major stroke as the qualifying stroke event for the trial.

PFO closure for secondary prevention

Stephan Windecker, MD, from the Swiss Cardiovascular Center, Bern, Switzerland, presented results from the PC Trial demonstrating that PFO closure with the Amplatzer PFO Occluder for secondary prevention of thromboembolism showed no significant reduction in ischemic and bleeding events compared with medical therapy.

The randomized trial compared the efficacy of percutaneous PFO closure with medical therapy in 414 patients with cryptogenic stroke and peripheral embolism. Medical treatment included oral anticoagulation or antiplatelet therapy at the discretion of the neurologist.

Windecker reported a relative risk reduction of 37% with the PFO closure device for the primary composite endpoint of all-cause death, nonfatal stroke, TIA and peripheral embolism that was not significant (HR=0.63; 95% CI 0.24-1.62; P=.34). Results also indicated no significant reduction in ischemic and bleeding events with the device vs. medical therapy (2.9% vs. 5.7%; HR=0.49; 95% CI 0.19-1.32; P=.16).

The relative risk reduction of stroke with the device was 80% (P=.14), with a number needed to treat of 40. The observed difference in stroke may be clinically relevant if confirmed in further studies, Windecker said.

Taking the field beyond ‘if’

Commenting on the results of the RESPECT and PC trials, Brian K. Whisenant, MD, of Intermountain Medical Group, Salt Lake City, Utah, said, “We now see strong, compelling evidence that there is stroke reduction with PFO closure if we truly identify the right patients.” However, it is going to be “extraordinarily difficult” to randomize patients for such trials in the future.

“From a medical device perspective, what we need in bringing devices forward is a regulatory pathway so we can evolve this field and take it beyond the major question of ‘if,” he said during the discussion.