• Neurology
• Interventional Techniques & Devices
• Episodic & Paroxysmal Disorders Clinical Trials

Lawrence Wechsler, MD, University of Pittsburgh, Pittsburgh, Pennsylvania, presented the results of the CLOSURE I trial (NCT00201461). This trial was conducted to determine if percutaneous patent foramen ovale (PFO) closure using the STARFlex® Septal Closure System in combination with medical therapy, is superior to medical therapy alone to prevent recurrent ischemic neurological symptoms in patients with transient ischemic attack (TIA) or ischemic stroke.

CLOSURE I was a prospective, randomized, open-label, two-arm superiority trial. The study population included patients ≤60 years of age with a cryptogenic TIA or stroke and PFO, with or without atrial septal aneurysm, within 6 months of randomization. The primary endpoint was the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurological mortality from ≥31 days of follow-up, as adjudicated by a panel of physicians who were unaware of treatment allocation.

At 87 sites in the United States and Canada, subjects were randomized to either best medical therapy (n=462; aspirin 325 mg daily or warfarin [target INR 2.0–3.0] or a combination of the two) or percutaneous PFO closure with the STARFlex® system within 30 days of randomization followed by clopidogrel 75 mg for 6 months and aspirin 325 mg for 24 months (n=447). The mean age of study participants was ∼46 years. Most (∼90%) were white, and approximately 50% were men. Large shunts were significantly (p=0.04) more common in the device group, and atrial septal aneurysms were present in about one-third of each group. About 70% of both groups had stroke as the entry event.

There was no significant difference between the two groups in the primary composite endpoint (5.9% in the device group and 7.7% in the medical group; p=0.30) or in either of the individual components: a 3.1% rate of stroke for the device group versus 3.4% for medical therapy (p=0.77); and a 3.3% rate of TIA for the device group versus 4.6% for medical therapy (p=0.39). No significant differences between the groups were noted when subjects with only subcortical or lacunar infarcts were excluded.

There were significantly more major vascular complications (eg, perforation; hematoma >5 cm at access site; retroperitoneal bleed) in the device group (3.2% vs 0.0% in the medical group; p<0.001). Significantly (p<0.001) more subjects in the device group experienced atrial fibrillation (AF; 5.7%) versus subjects in the medical group (0.7%). Sixty percent of the AF in the device group was periprocedural; 70% of AF lasted >24 hours. No significant relationship was identified between the rate of TIA or stroke and the presence of atrial septal aneurysm or the degree of PFO shunting. Recurrence rates did not differ between patients who presented with TIA versus stroke.

An alternative explanation was apparent for 80% of the recurrent strokes in this study, making it difficult to attribute them to paradoxical embolism. Potential alternate explanations for 9 of the 12 strokes in the device group were as follows: 3 were periprocedural, 3 subjects had typical lacunar events, 2 were associated with new AF, and one was related to cardiac catheterization. Alternative explanations were possible for the 13 strokes in the medical group: 8 subjects had multiple comorbidities (migraine, risk factors, etc), 4 were typical lacunar events, and one subject had possible vasculitis.

• © 2011 MD Conference Express