A systematic literature review of 20 studies to examine the efficacy of transcatheter closure compared to antithrombotic therapy showed that the annual risk of recurrent TIA or stroke was lower in the group with closure (1.3 %; 95 % CI 1.0 – 1.8) than in patients who received antithrombotic therapy (5.2 %; 95 % CI 4.4 – 6.2) (35). This applied in particular to patients with co-existing atrioseptal aneurysm.
Other studies have not shown any risk reduction with closure compared to antithrombotic treatment alone (2) – (4, 36). In a Norwegian study of 15 patients who underwent transcatheter closure, no recurrent cerebrovascular episodes occurred after a median follow-up period of nine months (33).
There are only three randomised studies of secondary prophylaxis for patients with TIA or ischaemic stroke and patent foramen ovale – CLOSURE (2), RESPECT (3) and PC (4).
In CLOSURE, 909 patients aged 18 – 60 were randomised (2). There was no significant difference in the incidence of the primary endpoint, which was a composite of recurrent stroke, TIA or death, after two years. The incidence was 5.5 % in patients with closure (n = 447) and 6.8 % in patients who received antithrombotic therapy (n = 462) (p = 0.37). In both groups, the two-year risk of recurrent stroke was lower than expected (almost 3 %) and in 81 % of the cases due to an etiology other than patent foramen ovale. Conversely, the proportion of TIAs (3.1 % and 4.1 %, respectively) was higher than expected. The results may indicate that the first cerebrovascular episode was not due to patent foramen ovale and that the underlying cause may have been overlooked.
The most common complications of transcatheter closure are dislocation of the closure device, groin haematoma, arteriovenous fistula, thrombus formation in the closure device, pulmonary embolism, haemorrhage, arrhythmia and cardiac tamponade (1). In CLOSURE, catheter treatment increased the absolute risk of serious vascular events by 3.2 % and of induced atrial fibrillation in 5.7 %. One objection to the high complication rates has been that several of the treatment centres involved had too little training and routine in the catheter technique. None of the patients died of neurological causes during the follow-up.
The CLOSURE study provides no evidence of a reduction of recurrent stroke after transcatheter closure of patent foramen ovale than after antithrombotic therapy alone. Subgroup analyses showed corresponding results for large openings with atrial septal aneurysm.
The CLOSURE study had a number of weaknesses, inter alia a low inclusion rate. It took five years to recruit 909 patients, and the average recruitment rate per centre was two patients per year (37). Patients with a number of other risk factors for stroke were also included, including age up to 60, hypertension, diabetes, atherosclerosis and smoking, all of which may represent bias. Not all patients underwent a cerebral MRI.
The medical treatment was heterogeneous: warfarin for 24 months or acetylsalisylic acid or a combination of the two. According to the study protocol, the patients in the group with closure were to use antiplatelet therapy, although 97 of the patients had previously been taking warfarin. The STARFlex closure device (NMT Medical) was used, but is no longer available on the market (38).
In RESPECT, 980 patients aged 18 – 60 were randomised and followed up for 2.5 years (3). The primary endpoint was recurrent stroke or death. There was no significant difference between the groups. The risk of recurrent stroke/death was 0.66 events/100 patient-years in the closure group and 1.38 in the antithrombotic therapy group (p = 0.08). Subgroup analyses showed a significant difference in favour of closure in cases with a large opening (p = 0.01) and co-existing atrial septal aneurism (p = 0.02). The study showed that selected patients with embolic stroke on an MRI scan, without vascular risk factors and with a large opening, may benefit from closure.
In PC, 414 patients were included over four years (4). There was no significant difference in the incidence of the primary end-point, a combination of recurrent stroke, TIA or death, after closure compared with antithrombotic therapy. The primary end-point occurred in 3.4 % of the patients with closure and in 5.2 % of those who received antithrombotic therapy (p = 0.34). Ischaemic stroke occurred in one patient (0.5 %) in the closure group and in five patients (2.4 %) in the group with antithrombotic therapy (p = 0.14). Subgroup analyses revealed a non-significant difference in favour of closure for patients aged < 45 and with co-existing atrial septal aneurism.
The AMPLATZER PFO Occluder device (St. Jude Medical) was used in both RESPECT and PC. The complication percentage was lower than in studies where the STARFlex closure device was used, which indicates a better safety profile. The incidence of atrial fibrillation with transcatheter technique was also lower in RESPECT (3.0 %) and in PC (2.9 %) than in CLOSURE (5.7 %).