RESPECT Confirms Long-term Safety, Efficacy of PFO Closure for Recurrent Stroke

Extended follow-up results of the RESPECT trial presented on Thursday at TCT 2015 support the safety and efficacy of patent foramen ovale (PFO) closure over medical management for reducing the risk of recurrent cryptogenic stroke. 

The main RESPECT trial, published in the New England Journal of Medicine in 2013, showed superiority of PFO closure in patients assigned to the Amplatzer PFO Occluder (St. Jude Medical; n = 499) compared with guideline-directed medical therapy with one or more antiplatelet medications or warfarin (n = 481) in prespecified per-protocol and as-treated analyses, but it found no significant benefit in the primary intention-to-treat analysis. The new findings provide follow-up of 5.5 years for the PFO occlusion arm and 4.9 years for the medical-therapy arm.

Procedure and Device Safe, Effective 

One of five patients were aged older than 60 years, and one-third of recurrent strokes arose from known mechanisms in the extended follow-up analysis, John D. Carroll, MD, of the University of Colorado, Denver, Co., said.

In the intention-to-treat population, the relative risk for recurrent cryptogenic stroke was reduced by more than half after PFO closure, according to Kaplan-Meier estimation at the end of follow-up.

Additionally, PFO closure reduced the relative risk of recurrent cryptogenic stroke by 70% compared with medical therapy (1.5% to 4.3%; P = .004).

One complicating factor of the extended analysis was that 20% of the original patients were no longer aged younger than 60 years, increasing their susceptibility to noncryptogenic strokes that PFO closure cannot prevent, Carroll said. “PFO closure can only reduce risk for recurrent strokes mediated by paradoxical embolism,” he noted.

In a sensitivity analysis limiting the intention-to-treat population to younger patients who were still in the 18- to 60-year-old range, there was still a 52% relative reduction in all-cause stroke risk with PFO closure vs medical management (log-rank P = .035).

PFO closure also conferred a 75% reduction in relative risk for cryptogenic stroke among patients with atrial septal aneurysms and substantial right-to-left shunts (log-rank P = .007).

Carroll concluded that procedure and device safety were bolstered by no evidence of intra-procedural stroke, device embolization, device thrombosis or erosion during extended follow-up. Rates of major vascular complications (0.9%) and device explantation (0.4%) also were very low, he noted.

“The Amplatzer PFO Occluder is superior to medical management in reducing recurrent cryptogenic ischemic stroke,” he said. “The treatment effect is fully manifest in types of strokes for which closure is intended, and superiority is substantial and sustained [over medical management].”

However, comprehensive risk-factor modification in this population remains an issue. “While PFO closure substantially decreases the risk of cryptogenic strokes, strokes of known mechanism emerge as patients age,” Carroll said.

“This is really not a 5-year problem,” added panelist Robert J. Sommer, MD, of NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, N.Y. “This is a lifelong problem for many of these patients.”

Disclosures:

• The study was funded by St. Jude Medical.
• Carroll reports receiving consultant fees from St. Jude Medical.