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Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA
Clinical question: Is the combination of aspirin and clopidogrel effective in reducing stroke recurrence?
Background: The risk of recurrent stroke varies from 3% to 15% in the 3 months after a minor ischemic stroke (NIH Stroke Scale score of 3 or less) or high-risk transient ischemic attack (ABCD2 score of 4 or less). Dual-antiplatelet therapy with aspirin and clopidogrel reduces recurrent coronary syndrome; therefore, this strategy can prevent recurrent stroke.
Study design: Prospective, randomized, double-blind, multicenter, placebo-controlled trial.
Setting: 269 sites in 10 countries, mostly in the United States, from May 28, 2010, to Dec. 19, 2017.
Synopsis: The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled 4,881 patients older than 18 years of age randomized to a loading dose of 600 mg of clopidogrel followed by 75 mg per day or placebo, and aspirin 162 mg daily for 5 days followed by 81 mg daily. The primary outcome was the risk of major ischemic events, including ischemic stroke, myocardial infarction, or death from ischemic vascular causes. Major ischemic events were observed in 5.0% receiving dual therapy and in 6.5% of those receiving aspirin alone (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95; P = .02) with most occurring within a week after the initial stroke. Major hemorrhage occurred in only 23 patients (0.9%), most of which were extracranial and nonfatal. One of the main limitations is the difficulty in objectively diagnosing TIAs, accounting for 43% of the patients in the study.
Bottom line: Dual-antiplatelet therapy with aspirin and clopidogrel is beneficial, mainly in the first week after a minor stroke or high-risk TIA with low risk of major bleeding.
Citation: Johnston SC et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-25.
Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver.
Clinical question: Is the combination of aspirin and clopidogrel effective in reducing stroke recurrence?
Background: The risk of recurrent stroke varies from 3% to 15% in the 3 months after a minor ischemic stroke (NIH Stroke Scale score of 3 or less) or high-risk transient ischemic attack (ABCD2 score of 4 or less). Dual-antiplatelet therapy with aspirin and clopidogrel reduces recurrent coronary syndrome; therefore, this strategy can prevent recurrent stroke.
Study design: Prospective, randomized, double-blind, multicenter, placebo-controlled trial.
Setting: 269 sites in 10 countries, mostly in the United States, from May 28, 2010, to Dec. 19, 2017.
Synopsis: The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled 4,881 patients older than 18 years of age randomized to a loading dose of 600 mg of clopidogrel followed by 75 mg per day or placebo, and aspirin 162 mg daily for 5 days followed by 81 mg daily. The primary outcome was the risk of major ischemic events, including ischemic stroke, myocardial infarction, or death from ischemic vascular causes. Major ischemic events were observed in 5.0% receiving dual therapy and in 6.5% of those receiving aspirin alone (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95; P = .02) with most occurring within a week after the initial stroke. Major hemorrhage occurred in only 23 patients (0.9%), most of which were extracranial and nonfatal. One of the main limitations is the difficulty in objectively diagnosing TIAs, accounting for 43% of the patients in the study.
Bottom line: Dual-antiplatelet therapy with aspirin and clopidogrel is beneficial, mainly in the first week after a minor stroke or high-risk TIA with low risk of major bleeding.
Citation: Johnston SC et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-25.
Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver.
Clinical question: Is the combination of aspirin and clopidogrel effective in reducing stroke recurrence?
Background: The risk of recurrent stroke varies from 3% to 15% in the 3 months after a minor ischemic stroke (NIH Stroke Scale score of 3 or less) or high-risk transient ischemic attack (ABCD2 score of 4 or less). Dual-antiplatelet therapy with aspirin and clopidogrel reduces recurrent coronary syndrome; therefore, this strategy can prevent recurrent stroke.
Study design: Prospective, randomized, double-blind, multicenter, placebo-controlled trial.
Setting: 269 sites in 10 countries, mostly in the United States, from May 28, 2010, to Dec. 19, 2017.
Synopsis: The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled 4,881 patients older than 18 years of age randomized to a loading dose of 600 mg of clopidogrel followed by 75 mg per day or placebo, and aspirin 162 mg daily for 5 days followed by 81 mg daily. The primary outcome was the risk of major ischemic events, including ischemic stroke, myocardial infarction, or death from ischemic vascular causes. Major ischemic events were observed in 5.0% receiving dual therapy and in 6.5% of those receiving aspirin alone (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95; P = .02) with most occurring within a week after the initial stroke. Major hemorrhage occurred in only 23 patients (0.9%), most of which were extracranial and nonfatal. One of the main limitations is the difficulty in objectively diagnosing TIAs, accounting for 43% of the patients in the study.
Bottom line: Dual-antiplatelet therapy with aspirin and clopidogrel is beneficial, mainly in the first week after a minor stroke or high-risk TIA with low risk of major bleeding.
Citation: Johnston SC et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-25.
Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver.
Rivaroxaban for stroke prevention after embolic stroke
Clinical question: Does rivaroxaban prevent recurrent ischemic stroke in patients with embolic stroke from undetermined source?
Background: Embolic stroke of undetermined source (ESUS) represents approximately 20% of ischemic strokes. Rivaroxaban inhibits factor Xa and is shown to be effective for secondary stroke prevention in patients with nonvalvular atrial fibrillation. Strategies to prevent cryptogenic stroke caused by mechanisms other than cardioembolic sources are lacking.
Study design: International, double-blind, event-driven, randomized, phase III trial.
Setting: 459 hospitals in 31 countries, during 2014-2017.
Synopsis: 7,213 patients with ESUS were randomized to receive either 15 mg of rivaroxaban once daily or aspirin 100 mg once daily. The primary outcome was established as the first recurrent stroke of any type or systemic embolism. The primary safety endpoint was major bleeding.
Recurrent stroke was observed in 158 in the rivaroxaban group and 156 in the aspirin group, mostly ischemic. The trial was terminated early because of a higher incidence of intracranial hemorrhage and major bleeding among patients assigned to rivaroxaban at an annual rate of 1.8%, compared with 0.7% (hazard ratio, 2.72; 95% confidence interval, 1.68-4.39; P less than .001). Although the study utilized strict criteria to define ESUS, it is feasible that the lack of benefit may be due to heterogeneous arterial, cardiogenic, and paradoxical emboli with diverse composition and poor response to rivaroxaban.
Bottom line: Rivaroxaban does not confer protection from recurrent stroke in patients with embolic stroke of unknown origin and increases risk for intracranial hemorrhage and major bleeding.
Citation: Hart RG et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-201.
Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver
Clinical question: Does rivaroxaban prevent recurrent ischemic stroke in patients with embolic stroke from undetermined source?
Background: Embolic stroke of undetermined source (ESUS) represents approximately 20% of ischemic strokes. Rivaroxaban inhibits factor Xa and is shown to be effective for secondary stroke prevention in patients with nonvalvular atrial fibrillation. Strategies to prevent cryptogenic stroke caused by mechanisms other than cardioembolic sources are lacking.
Study design: International, double-blind, event-driven, randomized, phase III trial.
Setting: 459 hospitals in 31 countries, during 2014-2017.
Synopsis: 7,213 patients with ESUS were randomized to receive either 15 mg of rivaroxaban once daily or aspirin 100 mg once daily. The primary outcome was established as the first recurrent stroke of any type or systemic embolism. The primary safety endpoint was major bleeding.
Recurrent stroke was observed in 158 in the rivaroxaban group and 156 in the aspirin group, mostly ischemic. The trial was terminated early because of a higher incidence of intracranial hemorrhage and major bleeding among patients assigned to rivaroxaban at an annual rate of 1.8%, compared with 0.7% (hazard ratio, 2.72; 95% confidence interval, 1.68-4.39; P less than .001). Although the study utilized strict criteria to define ESUS, it is feasible that the lack of benefit may be due to heterogeneous arterial, cardiogenic, and paradoxical emboli with diverse composition and poor response to rivaroxaban.
Bottom line: Rivaroxaban does not confer protection from recurrent stroke in patients with embolic stroke of unknown origin and increases risk for intracranial hemorrhage and major bleeding.
Citation: Hart RG et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-201.
Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver
Clinical question: Does rivaroxaban prevent recurrent ischemic stroke in patients with embolic stroke from undetermined source?
Background: Embolic stroke of undetermined source (ESUS) represents approximately 20% of ischemic strokes. Rivaroxaban inhibits factor Xa and is shown to be effective for secondary stroke prevention in patients with nonvalvular atrial fibrillation. Strategies to prevent cryptogenic stroke caused by mechanisms other than cardioembolic sources are lacking.
Study design: International, double-blind, event-driven, randomized, phase III trial.
Setting: 459 hospitals in 31 countries, during 2014-2017.
Synopsis: 7,213 patients with ESUS were randomized to receive either 15 mg of rivaroxaban once daily or aspirin 100 mg once daily. The primary outcome was established as the first recurrent stroke of any type or systemic embolism. The primary safety endpoint was major bleeding.
Recurrent stroke was observed in 158 in the rivaroxaban group and 156 in the aspirin group, mostly ischemic. The trial was terminated early because of a higher incidence of intracranial hemorrhage and major bleeding among patients assigned to rivaroxaban at an annual rate of 1.8%, compared with 0.7% (hazard ratio, 2.72; 95% confidence interval, 1.68-4.39; P less than .001). Although the study utilized strict criteria to define ESUS, it is feasible that the lack of benefit may be due to heterogeneous arterial, cardiogenic, and paradoxical emboli with diverse composition and poor response to rivaroxaban.
Bottom line: Rivaroxaban does not confer protection from recurrent stroke in patients with embolic stroke of unknown origin and increases risk for intracranial hemorrhage and major bleeding.
Citation: Hart RG et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-201.
Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver