Comparative efficacy and safety of multiple antiplatelet therapies for secondary prevention of ischemic stroke or transient ischemic attack: A network meta-analysis. 2019

Rong-Wu Xiang, and Ruo-Bing Han, and Jing-Yu Yang, and Ming-Yi Zhao, and Qing-Chun Zhao, and Hui-Sheng Chen, and Fang-Qing Zhao, and Zhong-Yi Sun, and Tong Zhao, and Ting-Yan Song
Department of Clinical Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, Liaoning, China. Electronic address: xrwlove@163.com.

BACKGROUND Antiplatelet therapies for secondary prevention of ischemic stroke or transient ischemic attack (TIA) is a highly active research topic with five critical drugs obtained by visual analysis. We aimed to compare and rank multiple antiplatelet therapies using a network meta-analysis. METHODS Relevant medical databases were searched. Eligible randomized controlled trials (RCTs) which examined any comparisons involving mono- or dual antiplatelet therapies, based on aspirin, clopidogrel, dipyridamole, ticlopidine, cilostazol and placebo for patients with noncardioembolic ischemic stroke or TIA, were included. 14 outcomes were assessed. Primary outcomes were stroke recurrence, composite events (stroke recurrence, myocardial infarction and vascular death), and intracranial hemorrhage. PROSPERO registered number CRD42017069728. RESULTS 45 RCTs with 173,131 patients were included in network meta-analysis, involving eight antiplatelet therapies. Cilostazol and clopidogrel were statistically more efficacious than aspirin (odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.47-0.88; OR = 0.77, 95%CI = 0.62-0.95) and dipyridamole (OR = 0.64, 95%CI = 0.44-0.93; OR = 0.76, 95%CI = 0.58-0.99) in reducing stroke recurrence, and showed significant benefits in reducing composite events compared with aspirin (OR = 0.63, 95%CI = 0.45-0.89; OR = 0.90, 95%CI = 0.83-0.97). No significant difference was found between cilostazol and clopidogrel in intracranial hemorrhage. Weighted regression suggested cilostazol was hierarchically the optimum treatment in consideration of both efficacy and safety, followed by clopidogrel. CONCLUSIONS Cilostazol and clopidogrel are probably promising options for secondary prevention of ischemic stroke or TIA. Both of them reduce stroke recurrence similarly compared with aspirin or dipyridamole, and reduce composite events compared with aspirin. Further studies are needed to confirm this finding.

UI MeSH Term Description Entries
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D002546 Ischemic Attack, Transient Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6) Brain Stem Ischemia, Transient,Cerebral Ischemia, Transient,Crescendo Transient Ischemic Attacks,Transient Ischemic Attack,Anterior Circulation Transient Ischemic Attack,Brain Stem Transient Ischemic Attack,Brain TIA,Brainstem Ischemia, Transient,Brainstem Transient Ischemic Attack,Carotid Circulation Transient Ischemic Attack,Posterior Circulation Transient Ischemic Attack,TIA (Transient Ischemic Attack),Transient Ischemic Attack, Anterior Circulation,Transient Ischemic Attack, Brain Stem,Transient Ischemic Attack, Brainstem,Transient Ischemic Attack, Carotid Circulation,Transient Ischemic Attack, Posterior Circulation,Transient Ischemic Attack, Vertebrobasilar Circulation,Transient Ischemic Attacks, Crescendo,Vertebrobasilar Circulation Transient Ischemic Attack,Attack, Transient Ischemic,Attacks, Transient Ischemic,Brainstem Ischemias, Transient,Cerebral Ischemias, Transient,Ischemia, Transient Brainstem,Ischemia, Transient Cerebral,Ischemias, Transient Brainstem,Ischemias, Transient Cerebral,Ischemic Attacks, Transient,TIA, Brain,TIAs (Transient Ischemic Attack),Transient Brainstem Ischemia,Transient Cerebral Ischemia,Transient Cerebral Ischemias,Transient Ischemic Attacks
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071076 Network Meta-Analysis Meta-analysis of randomized trials in which estimates of comparative treatment effects are visualized and interpreted from a network of interventions that may or may not have been evaluated directly against each other. Common considerations in network meta-analysis include conceptual and statistical heterogeneity and incoherence. Mixed Treatment Meta-Analysis,Multiple Treatment Comparison Meta-Analysis,Meta-Analyses, Mixed Treatment,Meta-Analyses, Network,Meta-Analysis, Mixed Treatment,Meta-Analysis, Network,Mixed Treatment Meta Analysis,Mixed Treatment Meta-Analyses,Multiple Treatment Comparison Meta Analysis,Network Meta Analysis,Network Meta-Analyses
D055502 Secondary Prevention The prevention of recurrences or exacerbations of a disease or complications of its therapy. Disease Prevention, Secondary,Early Therapy,Relapse Prevention,Secondary Disease Prevention,Disease Preventions, Secondary,Early Therapies,Prevention, Relapse,Prevention, Secondary,Prevention, Secondary Disease,Preventions, Relapse,Preventions, Secondary,Preventions, Secondary Disease,Relapse Preventions,Secondary Disease Preventions,Secondary Preventions,Therapies, Early,Therapy, Early
D020521 Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810) Apoplexy,Cerebral Stroke,Cerebrovascular Accident,Cerebrovascular Apoplexy,Vascular Accident, Brain,CVA (Cerebrovascular Accident),Cerebrovascular Accident, Acute,Cerebrovascular Stroke,Stroke, Acute,Acute Cerebrovascular Accident,Acute Cerebrovascular Accidents,Acute Stroke,Acute Strokes,Apoplexy, Cerebrovascular,Brain Vascular Accident,Brain Vascular Accidents,CVAs (Cerebrovascular Accident),Cerebral Strokes,Cerebrovascular Accidents,Cerebrovascular Accidents, Acute,Cerebrovascular Strokes,Stroke, Cerebral,Stroke, Cerebrovascular,Strokes,Strokes, Acute,Strokes, Cerebral,Strokes, Cerebrovascular,Vascular Accidents, Brain

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