Trial Summary CLOSURE I
Title: Safety and Efficacy of the STARFlex Septal Closure System vs. Best Medical Therapy in Patients With a Stroke or TIA due to Presumed Paradoxical Embolism Through a PFO
Trial Sponsor: NMT
Year Presented: 2010
Topic(s): Congenital Heart Disease, General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 11/15/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE)
Description:
The goal of the trial was to evaluate percutaneous closure of a patent foramen ovale (PFO) compared with medical therapy among patients with a cryptogenic stroke or transient ischemic attack (TIA).
Hypothesis:
PFO closure will be more effective in reducing the risk of recurrent stroke/TIA.
Drugs/Procedures Used:
Patients with cryptogenic stroke or TIA presumably due to a PFO were randomized to PFO closure with the STARFlex device (n = 447) versus medical therapy (n = 462).
Concomitant Medications:
Patients who underwent PFO closure were treated with clopidogrel 75 mg daily for 6 months and aspirin 325 mg daily for 2 years.
Patients who received medical therapy alone were treated with aspirin 325 mg daily, or warfarin with international normalized ratio (INR) target 2 to 3, or combination aspirin and warfarin.
Principal Findings:
Overall, 909 patients were randomized. In the STARFlex group, the mean age was 46 years, 48% were women, and 38% had an atrial septal aneurysm ≥10 mm. Procedural success was achieved in 90%, and 87% of participants had no or trace residual shunt by transesophageal echocardiography at 24 months.
The primary outcome, recurrent stroke or TIA within 2 years, all-cause mortality within 30 days, or neurological mortality between 31 days and 2 years occurred in 5.9% of the PFO closure group versus 7.7% of the medical therapy group (p = 0.30). Within 2 years, the number of strokes that occurred was 12 versus 13 (p = 0.77), and the number of TIAs was 13 versus 17 (p = 0.39), respectively, for PFO closure versus medical therapy. There was no difference in the primary outcome based on degree of residual shunt or presence of an atrial septal aneurysm. Within the medical arm, there was no difference in the primary outcome for aspirin alone versus warfarin alone.
Of the 12 strokes in the PFO closure group, three were procedure related, three were recurrent cryptogenic stroke, and six were due to an alternative etiology such as atrial fibrillation or a lacunar stroke. Of the 13 strokes in the medical group, one was due to recurrent cryptogenic stroke, whereas the rest were due to an alternative etiology such as atrial fibrillation, complex migraine, vasculitis, or lacunar stroke.
Major vascular complications (left atrial perforation, groin hematoma, vascular surgical repair, peripheral nerve injury, procedure-related transfusion, and retroperitoneal bleed) occurred in 3.2% versus 0 (p < 0.001), atrial fibrillation occurred in 5.7% versus 0.7% (p < 0.001), and major bleeding occurred in 2.6% versus 1.1% (p = 0.11), respectively, for PFO closure versus medical therapy.
Interpretation:
Among patients with cryptogenic stroke/TIA, percutaneous PFO closure with the STARFlex device was not superior to medical therapy. Percutaneous PFO closure did not reduce the incidence of the primary outcome at 2 years, nor did it reduce the incidence of stroke or TIA. Moreover, PFO closure was also associated with major vascular complications and an excess in atrial fibrillation compared with medical therapy. Multiple alternative etiologies were discovered for recurrent stroke, which illustrates the difficulty in diagnosing cryptogenic stroke. At the present time, routine closure of PFO for cryptogenic stroke patients cannot be recommended.
Epidemiological data support an association between PFO and cryptogenic stroke; however, clinical trial data regarding PFO closure are sparse. CLOSURE I findings were not due to lack of power or lower than expected event rate: The primary outcome was expected to occur in 2% of the device arm (5.9% actual), whereas the primary outcome was expected to occur in 6% of the medical arm (7.7% actual). Long-term follow-up of these patients is warranted. Ongoing trials include CLOSE and PC-Trial.
Study Design:
Randomized. Blinded. Parallel. Stratified.
Primary Endpoints:
Composite of recurrent stroke or TIA within 2 years, all-cause mortality within 30 days, or neurological mortality between 31 days and 2 years
Patient Population:
Patients with cryptogenic stroke/TIA and PFO with or without atrial septal aneurysm diagnosed in the previous 6 months
Number of enrollees: 909
Duration of follow-up: 2 years
Mean patient age: 46 years
Percentage female: 48%
Exclusions:
Deep vein thrombosis or hypercoagulable state
References:
Presented by Dr. Anthony Furlan at the American Heart Association Scientific Sessions, Chicago, IL, November 15, 2010.