TY - JOUR
T1 - Association of recent use of non–Vitamin K antagonist oral anticoagulants with intracranial hemorrhage among patients with acute ischemic stroke treated with alteplase
AU - Kam, Wayneho
AU - Holmes, Da Juanicia N.
AU - Hernandez, Adrian F.
AU - Saver, Jeffrey L.
AU - Fonarow, Gregg C.
AU - Smith, Eric E.
AU - Bhatt, Deepak L.
AU - Schwamm, Lee H.
AU - Reeves, Mathew J.
AU - Matsouaka, Roland A.
AU - Khan, Yosef M.
AU - Unverdorben, Martin
AU - Birmingham, Mary C.
AU - Lyden, Patrick D.
AU - Asimos, Andrew W.
AU - Altschul, Dorothea
AU - Schoonover, Timothy L.
AU - Jumaa, Mouhammad A.
AU - Nomura, Jason T.
AU - Suri, Muhammad Fareed K.
AU - Moore, S. Arthur
AU - Lafranchise, Eugene F.
AU - Olson, Dai Wai
AU - Peterson, Eric D.
AU - Xian, Ying
N1 - Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/2/22
Y1 - 2022/2/22
N2 - IMPORTANCE Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non–vitamin K antagonist oral anticoagulants (NOACs). OBJECTIVE To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines–Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. EXPOSURES Prestroke treatment with NOACs within 7 days prior to alteplase treatment. MAIN OUTCOMES AND MEASURES The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. RESULTS Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], −0.51% [95% CI, −1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, −1.20% [95% CI, −2.39% to −0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.
AB - IMPORTANCE Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non–vitamin K antagonist oral anticoagulants (NOACs). OBJECTIVE To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines–Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. EXPOSURES Prestroke treatment with NOACs within 7 days prior to alteplase treatment. MAIN OUTCOMES AND MEASURES The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. RESULTS Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], −0.51% [95% CI, −1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, −1.20% [95% CI, −2.39% to −0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.
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U2 - 10.1001/jama.2022.0948
DO - 10.1001/jama.2022.0948
M3 - Article
C2 - 35143601
AN - SCOPUS:85124766178
SN - 0098-7484
VL - 327
SP - 760
EP - 771
JO - JAMA
JF - JAMA
IS - 8
ER -