TY - JOUR

T1 - Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source

AU - Hart, Robert G

AU - Sharma, Mukul

AU - Mundl, Hardi

AU - Kasner, Scott E

AU - Bangdiwala, Shrikant I

AU - Berkowitz, Scott D

AU - Swaminathan, Balakumar

AU - Lavados, Pablo

AU - Wang, Yongjun

AU - Wang, Yilong

AU - Davalos, Antonio

AU - Shamalov, Nikolay

AU - Mikulik, Robert

AU - Cunha, Luis

AU - Lindgren, Arne

AU - Arauz, Antonio

AU - Lang, Wilfried

AU - Czlonkowska, Anna

AU - Eckstein, Jens

AU - Gagliardi, Rubens J

AU - Amarenco, Pierre

AU - Ameriso, Sebastian F

AU - Tatlisumak, Turgut

AU - Veltkamp, Roland

AU - Hankey, Graeme J

AU - Toni, Danilo

AU - Bereczki, Daniel

AU - Uchiyama, Shinichiro

AU - Ntaios, George

AU - Yoon, Byung-Woo

AU - Brouns, Raf

AU - Endres, Matthias

AU - Muir, Keith W

AU - Bornstein, Natan

AU - Ozturk, Serefnur

AU - O'Donnell, Martin J

AU - De Vries Basson, Matthys M

AU - Pare, Guillaume

AU - Pater, Calin

AU - Kirsch, Bodo

AU - Sheridan, Patrick

AU - Peters, Gary

AU - Weitz, Jeffrey I

AU - Peacock, W Frank

AU - Shoamanesh, Ashkan

AU - Benavente, Oscar R

AU - Joyner, Campbell

AU - Themeles, Ellison

AU - Connolly, Stuart J

AU - NAVIGATE ESUS Investigators

AU - Amarenco, P.

AU - Ameriso, S.F.

AU - Arauzo, A.

AU - Andersen, G.

AU - Christensen, H.

AU - Christensen, T.

AU - Damgaard, D.

AU - Iversen, H.

AU - Hansen, C. Krarup

AU - Kruuse, C.

AU - Martinussen, M.

AU - Modrau, B.

AU - Murtuzova, A.

AU - Ovesen, C.

AU - Papina, M.

AU - Svaneborg, N.

AU - Von Weitzel-Mudersbach, P.

AU - Xiong, W.

AU - Zhang, C.

AU - Zweifler, R.

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin.METHODS: We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding.RESULTS: A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001).CONCLUSIONS: Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

AB - BACKGROUND: Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin.METHODS: We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding.RESULTS: A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001).CONCLUSIONS: Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

KW - Aged

KW - Aspirin/adverse effects

KW - Brain Ischemia/prevention & control

KW - Factor Xa Inhibitors/adverse effects

KW - Female

KW - Hemorrhage/chemically induced

KW - Humans

KW - Intracranial Embolism/drug therapy

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Platelet Aggregation Inhibitors/adverse effects

KW - Rivaroxaban/adverse effects

KW - Secondary Prevention/methods

KW - Stroke/etiology

U2 - 10.1056/NEJMoa1802686

DO - 10.1056/NEJMoa1802686

M3 - Journal article

C2 - 29766772

VL - 378

SP - 2191

EP - 2201

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -