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Patent Foramen Ovale and Stroke A Review

Author/s: 
David M. Kent, Andy Y. Wang

Importance: A patent foramen ovale (PFO), an opening between the right and left atria during normal fetal development that fails to close after birth, is present in approximately 25% of all adults. Paradoxical embolism, a venous thromboembolism that travels to the systemic circulation typically through a PFO, accounts for about 5% of all strokes and 10% of strokes in younger patients.

Observations: Approximately 50% of patients 60 years or younger with an embolic stroke of undetermined source (cryptogenic stroke) have a PFO, compared with 25% of the general population. The Risk of Paradoxical Embolism (RoPE) score incorporates clinical characteristics (age, history of stroke or transient ischemic attack, diabetes, hypertension, smoking, cortical infarct on imaging) to predict the likelihood that embolic stroke of undetermined source was caused by a PFO. Among patients in the lowest RoPE score category (score <3), PFO prevalence was similar to that in the general population (23%), while PFO prevalence was 77% in patients with a RoPE score of 9 or 10. The PFO-Associated Stroke Causal Likelihood (PASCAL) classification system combines the RoPE score and anatomical criteria from echocardiography (large shunt, atrial septal aneurysm) to classify PFO as the “probable,” “possible,” or “unlikely” cause of otherwise cryptogenic stroke. PFO closure reduces recurrent ischemic stroke in patients 60 years or younger with cryptogenic stroke. In a pooled analysis of 6 trials (3740 patients), the annualized incidence of stroke over a median follow-up of 57 months was 0.47% (95% CI, 0.35%-0.65%) with PFO closure vs 1.09% (95% CI, 0.88%-1.36%) with medical therapy (adjusted hazard ratio, 0.41 [95% CI, 0.28-0.60]). However, the benefits and harms of closure were highly heterogeneous across the trial populations. In patients categorized as PASCAL “probable” (ie, younger patients without vascular risk factors and high-risk PFO anatomical features), there was a 90% decreased relative rate of recurrent ischemic stroke after PFO closure at 2 years (hazard ratio, 0.10 [95% CI, 0.03-0.35]; absolute risk reduction, 2.1% [95% CI, 0.9%-3.4%]). PASCAL “unlikely” patients (eg, older patients with vascular risk factors and no high-risk PFO anatomical features) did not have a lower recurrent stroke rate with PFO closure but had higher risk of procedure- and device-related adverse events, such as atrial fibrillation.

Conclusions and Relevance: Patent foramen ovale is present in approximately 25% of all adults and is a common cause of stroke in young and middle-aged patients. The PASCAL classification system can help guide patient selection for PFO closure. Percutaneous PFO closure substantially reduces the risk of stroke recurrence in well-selected patients younger than 60 years after cryptogenic stroke.

Keywords 
Congenital Defects pediatrics female

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis The CASSISS Randomized Clinical Trial

Author/s: 
Gao, P., Wang, T., Wang, D., Liebeskind, D. S.", H., Li, T., Zhao, Z., Cai, Y., Wu, W., He, W., Yu, J., Zheng, B., Wang, H., Wu, Y., Dmytriw, A. A., Krings, T., Derdeyn, C. P., Jiao, L., CASSISS Trial Investigators

Importance: Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.

Objective: To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis.

Design, setting, and participants: Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019).

Interventions: Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control.

Main outcomes and measures: The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years.

Results: Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08).

Conclusions and relevance: Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis.

Trial registration: ClinicalTrials.gov Identifier: NCT01763320.

Keywords 
randomized controlled trial Multicenter Study Treatment Outcome Pathologic Constriction stroke Stent
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