DOI: 10.1161/CIRCULATIONAHA.114.014791
Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE): 1-Year Outcomes Running title: Wang et al.; One year outcomes of the CHANCE trial Yilong Wang, MD, PhD1,2,3,4*; Yuesong Pan, MD1,2,3,4*; Xingquan Zhao, MD, PhD1,2,3,4; Hao Li, PhD1,2,3,4; David Wang, DO5; S. Claiborne Johnston, MD, PhD6; Liping Liu, MD, PhD1,2,3,4; Xia Meng, MD, PhD1,2,3,4; Anxin Wang, MD1,2,3,4; Chunxue Wang, MD, PhD1,2,3,4; Yongjun Wang, MD1,2,3,4, on behalf of the CHANCE investigators** 1 2
Dept of Neurology, Beijing Tiantan Hospital, Capital Medical University, Be Beijing, eijin ingg, in g, C China; hina hi na;; na
China National Clinical Research Center for Neurological Diseases, Beijing, China; 3Center of Stroke, Beijin Beijing ingg Institute for Brain Disorders, Beijing, China; 4Beijin Beijing ng Key Laboratory of
Translational Tran Tr anslationa an nal Medicine for Cerebrovascular Disease, na Diseeasse, Beiji Beijing, j ng, Ch China; hina; 5INI Stroke Network, OSF H Healthcare ealthcare Syste System, em, U University niiverssity ity off IIllinois llin ll noiis Co College olllegee ooff Me Medic Medicine, cinne, Pe Peoria, IL IL; L; 6De Dell M Medical edicaal S ed School, ch hoo ol University Univ Un i errsi iv sity y off Texas Teexaas att Austin, Ausstiin, Austin, Austi ust n, TX TX *contributed equ equally q ally y **A complete list of the CHANCE investigators can be found in the Supplemental Material Address for Correspondence: Yongjun Wang, MD Beijing Tiantan Hospital No.6 Tiantanxili Dongcheng District, Beijing, China, 100050 Tel: 0086-010-67098350 Fax: 0086-010-67013383 E-mail: [email protected] Journal Subject Codes: Stroke treatment - surgical:[81] Transient ischemic attacks, Stroke treatment - medical:[71] Anti platelets
1 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on May 10, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014791
Abstract
Background—The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combine treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage compared with aspirin alone, but provided insufficient data to establish whether the benefit persisted over longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. Methods and Results—The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin n ttherapy hera he rapy ra py (loading loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for aspirin 90 days, day ays, s, plus plu luss 75 mgof mgof aspirin per day for the first firs rsst 21 2 days) or to the asp piri r n alone group (75 mg primary outcome stroke hemorrhagic) pper er day for 90 ddays). a s). Th ay Thee pr prim im maryy ou outc tcom tc me wa was st tro oke eevent vent n ((ischemic nt issch c em emic icc orr he emo morrrha hagi g c) dduring urin ur ingg 1 in year Differences between were Cox proportional ye ear ffollow-up. ollow--up u . Di Differ ren nces of ooutcomes utco com co mess be etw tween ggroups roup upss w up erre re aassessed sses ss esse es s d uusing sin ng Co C x pr prop porrtionnall hazard haza ha zard ard model. mod odel el. Stroke el Stro St roke ro ke occurred occ ccur urre rre redd in 275(10.6%) 275 75(1 (100.6% (1 6%)) patients 6% pati pa tien ti ents en ts in in the the clopidogrel-aspirin clop cl opid op idog id ogre og rell-as re aspi as piri pi rinn group, ri grou gr oupp, as as compared with 362(14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65 to 0.93; P=0.006). Moderate-or-severe hemorrhage occurred in 7(0.3%) patients in the clopidogrel-aspirin group and 9 (0.4%) in the aspirin group (P = 0.44). Conclusions—The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted over the duration of 1 year of follow-up. Clinical Trial Registration Information— www.clinicaltrials.gov. Identifier: NCT00979589.
Key words: clopidogrel, outcome, stroke, transient ischemic attack
2 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on May 10, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014791
Introduction The early risk of recurrence of stroke following index transient ischemic attack (TIA) or minor ischemic stroke is very high, even in patients treated with aspirin.1,2,3 The Clopidogrel in Highrisk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial was designed to assess whether the combination treatment of clopidogrel and aspirin taken soon after a TIA or minor stroke could reduce the early risk of stroke.4 The original study termination of the CHANCE trial was 90 days from randomization, and the results showed that clopidogrel-aspirin treatment decreases the 90-day risk of stroke (hazard ratio=0.68, 95%CI: 0.57-0.81, P
Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE): 1-Year Outcomes Running title: Wang et al.; One year outcomes of the CHANCE trial Yilong Wang, MD, PhD1,2,3,4*; Yuesong Pan, MD1,2,3,4*; Xingquan Zhao, MD, PhD1,2,3,4; Hao Li, PhD1,2,3,4; David Wang, DO5; S. Claiborne Johnston, MD, PhD6; Liping Liu, MD, PhD1,2,3,4; Xia Meng, MD, PhD1,2,3,4; Anxin Wang, MD1,2,3,4; Chunxue Wang, MD, PhD1,2,3,4; Yongjun Wang, MD1,2,3,4, on behalf of the CHANCE investigators** 1 2
Dept of Neurology, Beijing Tiantan Hospital, Capital Medical University, Be Beijing, eijin ingg, in g, C China; hina hi na;; na
China National Clinical Research Center for Neurological Diseases, Beijing, China; 3Center of Stroke, Beijin Beijing ingg Institute for Brain Disorders, Beijing, China; 4Beijin Beijing ng Key Laboratory of
Translational Tran Tr anslationa an nal Medicine for Cerebrovascular Disease, na Diseeasse, Beiji Beijing, j ng, Ch China; hina; 5INI Stroke Network, OSF H Healthcare ealthcare Syste System, em, U University niiverssity ity off IIllinois llin ll noiis Co College olllegee ooff Me Medic Medicine, cinne, Pe Peoria, IL IL; L; 6De Dell M Medical edicaal S ed School, ch hoo ol University Univ Un i errsi iv sity y off Texas Teexaas att Austin, Ausstiin, Austin, Austi ust n, TX TX *contributed equ equally q ally y **A complete list of the CHANCE investigators can be found in the Supplemental Material Address for Correspondence: Yongjun Wang, MD Beijing Tiantan Hospital No.6 Tiantanxili Dongcheng District, Beijing, China, 100050 Tel: 0086-010-67098350 Fax: 0086-010-67013383 E-mail: [email protected] Journal Subject Codes: Stroke treatment - surgical:[81] Transient ischemic attacks, Stroke treatment - medical:[71] Anti platelets
1 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on May 10, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014791
Abstract
Background—The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combine treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage compared with aspirin alone, but provided insufficient data to establish whether the benefit persisted over longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. Methods and Results—The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin n ttherapy hera he rapy ra py (loading loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for aspirin 90 days, day ays, s, plus plu luss 75 mgof mgof aspirin per day for the first firs rsst 21 2 days) or to the asp piri r n alone group (75 mg primary outcome stroke hemorrhagic) pper er day for 90 ddays). a s). Th ay Thee pr prim im maryy ou outc tcom tc me wa was st tro oke eevent vent n ((ischemic nt issch c em emic icc orr he emo morrrha hagi g c) dduring urin ur ingg 1 in year Differences between were Cox proportional ye ear ffollow-up. ollow--up u . Di Differ ren nces of ooutcomes utco com co mess be etw tween ggroups roup upss w up erre re aassessed sses ss esse es s d uusing sin ng Co C x pr prop porrtionnall hazard haza ha zard ard model. mod odel el. Stroke el Stro St roke ro ke occurred occ ccur urre rre redd in 275(10.6%) 275 75(1 (100.6% (1 6%)) patients 6% pati pa tien ti ents en ts in in the the clopidogrel-aspirin clop cl opid op idog id ogre og rell-as re aspi as piri pi rinn group, ri grou gr oupp, as as compared with 362(14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65 to 0.93; P=0.006). Moderate-or-severe hemorrhage occurred in 7(0.3%) patients in the clopidogrel-aspirin group and 9 (0.4%) in the aspirin group (P = 0.44). Conclusions—The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted over the duration of 1 year of follow-up. Clinical Trial Registration Information— www.clinicaltrials.gov. Identifier: NCT00979589.
Key words: clopidogrel, outcome, stroke, transient ischemic attack
2 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on May 10, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014791
Introduction The early risk of recurrence of stroke following index transient ischemic attack (TIA) or minor ischemic stroke is very high, even in patients treated with aspirin.1,2,3 The Clopidogrel in Highrisk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial was designed to assess whether the combination treatment of clopidogrel and aspirin taken soon after a TIA or minor stroke could reduce the early risk of stroke.4 The original study termination of the CHANCE trial was 90 days from randomization, and the results showed that clopidogrel-aspirin treatment decreases the 90-day risk of stroke (hazard ratio=0.68, 95%CI: 0.57-0.81, P
