Antithrombotic Treatment in Cryptogenic Stroke Patients With Patent Foramen Ovale

Background and Purpose— It is unclear whether treatment with anticoagulants or antiplatelets is the optimal strategy in patients with stroke or transient ischemic attack of undetermined cause and patent foramen ovale that is not percutaneously closed. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare anticoagulant or antiplatelet treatment in this population. Methods— We searched PubMed until July 16, 2019 for trials comparing anticoagulants and antiplatelet treatment in patients with stroke/transient ischemic attack and medically treated patent foramen ovale using the terms: “cryptogenic or embolic stroke of undetermined source” and “stroke or cerebrovascular accident or transient ischemic attack” and “patent foramen ovale or patent foramen ovale or paradoxical embolism” and “trial or study” and “antithrombotic or anticoagulant or antiplatelet.” The outcomes assessed were stroke recurrence, major bleeding, and the composite end point of stroke recurrence or major bleeding. We used 3 random-effects models: (1) a reference model based on the inverse variance method with the Sidik and Jonkman heterogeneity estimator; (2) a strict model, implementing the Hartung and Knapp method; and (3) a commonly used Bayesian model with a prior that assumes moderate to large between-study variance. Results— Among 112 articles identified in the literature search, 5 randomized controlled trials were included in the meta-analysis (1720 patients, mean follow-up 2.3±0.5 years). Stroke recurrence occurred at a rate of 1.73 per 100 patient-years in anticoagulant-assigned patients and 2.39 in antiplatelet-assigned patients (hazard ratio, 0.68; 95% CI, 0.32–1.48 for the Sidik and Jonkman estimator). Major bleeding occurred at a rate of 1.16 per 100 patient-years in anticoagulant-assigned patients and 0.68 in antiplatelet-assigned patients (hazard ratio, 1.61; 95% CI, 0.72–3.59 for the Sidik and Jonkman estimator). The composite outcome occurred in 52 anticoagulant-assigned and 54 antiplatelet-assigned patients (odds ratio, 1.05; 95% CI, 0.65–1.70 for the Sidik and Jonkman estimator). Conclusions— We cannot exclude a large reduction of stroke recurrence in anticoagulant-assigned patients compared with antiplatelet-assigned, without significant differences in major bleeding. An adequately powered randomized controlled trial of a non–vitamin K antagonist versus aspirin is warranted.

Download Full-text

Clinical Effects of Dual Antiplatelet Therapy or Aspirin Monotherapy after Acute Minor Ischemic Stroke or Transient Ischemic Attack, a Meta-Analysis

Current Pharmaceutical Design ◽

10.2174/1381612827666210728102459 ◽

2021 ◽

Vol 27 ◽

Author(s):

Francesco Condello ◽

Gaetano Liccardo ◽

Giuseppe Ferrante

Keyword(s):

Ischemic Stroke ◽

Major Bleeding ◽

Transient Ischemic Attack ◽

Hemorrhagic Stroke ◽

Dual Antiplatelet Therapy ◽

Meta Analysis ◽

Stroke Recurrence ◽

Controlled Trials ◽

Minor Ischemic Stroke ◽

Ischemic Attack

Background: Evidence about the use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors in patients with acute minor ischemic stroke or transient ischemic attack (TIA) is emerging. The aim of our study was to provide an updated and comprehensive analysis about the risks and benefits of DAPT versus aspirin monotherapy in this setting. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov databases, main international conference proceedings were searched for randomized controlled trials comparing DAPT versus aspirin monotherapy in patients with acute ischemic stroke or TIA not eligible for thrombolysis or thrombectomy presenting in the first 24 hours after the acute event. Data were pooled by meta-analysis using a random-effects model. The primary efficacy endpoint was ischemic stroke recurrence, and the primary safety outcome was major bleeding. Secondary endpoints were intracranial hemorrhage, hemorrhagic stroke, and all-cause death. Results: A total of 4 studies enrolling 21,459 patients were included. DAPT with clopidogrel was used in 3 studies, DAPT with ticagrelor in one study. DAPT duration was 21 days in one study, 1 month in one study, and 3 months in the remaining studies. DAPT was associated with a significant reduction in the risk of ischemic stroke recurrence (relative risk [RR], 0.74; 95% confidence interval [CI], 0.67-0.82, P<0.001, number needed to treat 50 [95% CI 40-72], while it was associated with a significantly higher risk of major bleeding (RR, 2.59; 95% CI 1.49-4.53, P=0.001, number needed to harm 330 [95% CI 149-1111]), of intracranial hemorrhage (RR 3.06, 95% CI 1.41-6.66, P=0.005), with a trend towards higher risk of hemorrhagic stroke (RR 1.83, 95% CI 0.83-4.05, P=0.14), and a slight tendency towards higher risk of all-cause death (RR 1.30, 95% CI 0.89-1.89, P=0.16). Conclusions: Among patients with acute minor ischemic stroke or TIA, DAPT, as compared with aspirin monotherapy, might offer better effectiveness in terms of ischemic stroke recurrence at the expense of a higher risk of major bleeding. The trade-off between ischemic benefits and bleeding risks should be assessed in tailoring the therapeutic strategies.

Download Full-text