Courtesy of Dr. José Álvarez.

The RESPECT trial is a multicenter randomized trial with blinded adjudication of end-point events. It randomly assigned patients from 18 to 60 years of age who had a patent foramen ovale (PFO) and a history of cryptogenic ischemic stroke to undergo closure of the PFO with the Amplatzer device plus medical therapy or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with dipyridamole).

The efficacy endpoint was a composite of nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The first results of an average follow-up of 2.1 years have been reported previously. The current article includes results from the extended follow-up.

Results

The study enrolled 980 patients who were randomized as explained and followed for a mean 5.9 years. Treatment exposure was 3141 patient-years in the device group and 2669 patient-years in the medical-therapy group. This apparently unequal situation was a result of the rate of patients lost to follow-up: 20.8% for the first group and 33.3% for the second.

In the intention-to-treat analysis, recurrent ischemic stroke occurred in rates of 0.58 and 1.07 events per 100 patient-years in the device and medical-treatment groups, respectively (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.31 to 0.999; p = 0.046). Although, numerically, the divergence in the incidence of ischemic stroke was small, the relative difference resulted in 45% less events in the group randomized to the device. The prevention of an ischemic stroke event at 5 years required treating 43 patients with the device.

Read also: “Amplatzer and Figulla Devices Prove to Be Safe for Percutaneous Patent Foramen Ovale Closure”.

As regards the safety analysis, the rate of venous thromboembolism (a composite of events of pulmonary embolism and deep-vein thrombosis) was higher for the device group than for the medical-therapy group, although, surprisingly, both groups presented a high incidence of thromboembolic disease.

Additionally, there were 25 serious procedure-related adverse events, including atrial flutter and fibrillation, cardiac perforation, intracavity thrombosis, ischemic stroke, pulmonary embolism, etc., all of which were resolved during the first hospital stay.

Editorial

The Amplatzer PFO Occluder was approved by the FDA for patent foramen ovale closure in October, 2016. Results of the extended follow-up of the RESPECT trial (presented here) are considered beneficial no only due to the number of events prevented, but mainly due to their seriousness (recurrent stroke).

Read also: “Is Same-Day Discharge After Angioplasty Safe?”

These results match those of the other two studies published in the same issue of NEMJ: the CLOSE trial, which randomized patients with PFO and interatrial septum aneurysm or PFO and significant shunt, and used several closure devices; and the REDUCE trial, which used the GORE HELEX and CARDIOFORM devices, and in which follow-up included an MRI at 24 months for the detection of asymptomatic ischemic events.

The FDA warns that the Amplatzer PFO Occluder device may be used only in patients with cryptogenic stroke after detailed clinical assessment by a cardiologist and a neurologist.

Courtesy of Dr. José Álvarez.

Original title: Long Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

Reference: N Engl J Med 2017;377:1022-32

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