{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T04:23:50Z","timestamp":1746073430047},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Recent clinical trial data suggest that protease-activated receptor-1 (PAR-1) antagonists may increase the risk of intracranial hemorrhage. Our objective was to investigate the qualitative and quantitative risks of intracranial hemorrhage in patients receiving PAR-1 antagonist therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from 1966 to May 2012, were searched to identify relevant studies. We included randomized controlled trials that included a comparison of PAR-1 antagonist with placebo and in which the total number of patients and intracranial hemorrhage events were reported separately for active treatment and control groups. Summary incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using random-effects models. Between-study heterogeneity was assessed using the\n              <jats:italic>I<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              statistic.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              In 9 PAR-1 antagonist trials with 42000 patients with a history of thrombotic vascular disease or acute coronary syndrome, PAR-1 antagonist treatment was associated with increased risk of intracranial hemorrhage (0.59% vs 0.30%; relative risk, 1.98; 95% CI, 1.46\u20132.68;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.00001; number needed to harm, 345). There was no heterogeneity across trials (\n              <jats:italic>P<\/jats:italic>\n              =0.84;\n              <jats:italic>I<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =0%), PAR-1 antagonist agent (\n              <jats:italic>P<\/jats:italic>\n              =0.52), treatment duration (\n              <jats:italic>P<\/jats:italic>\n              =0.38), or trial-qualifying event (\n              <jats:italic>P<\/jats:italic>\n              =0.59). Risk of death from any cause or a cardiovascular cause did not differ between active treatment and control groups.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>In a pooled analysis of data from 9 trials, PAR-1 antagonist therapy was associated with an increased risk for intracranial hemorrhage.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.112.670604","type":"journal-article","created":{"date-parts":[[2012,11,17]],"date-time":"2012-11-17T02:20:39Z","timestamp":1353118839000},"page":"3189-3195","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Risk of Intracranial Hemorrhage With Protease-Activated Receptor-1 Antagonists"],"prefix":"10.1161","volume":"43","author":[{"given":"Meng","family":"Lee","sequence":"first","affiliation":[{"name":"From the Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi (M.L.) and Linkuo (H.-C.W.), Taiwan; Stroke Center, Geffen School of Medicine, University of California, Los Angeles, CA (J.L.S.); Department of Neurology, Ilsan Paik Hospital, Inje University, South Korea (K.-S.H.); and Department of Neurosciences, Medical University of South Carolina, Charleston, SC (B.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Saver","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi (M.L.) and Linkuo (H.-C.W.), Taiwan; Stroke Center, Geffen School of Medicine, University of California, Los Angeles, CA (J.L.S.); Department of Neurology, Ilsan Paik Hospital, Inje University, South Korea (K.-S.H.); and Department of Neurosciences, Medical University of South Carolina, Charleston, SC (B.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keun-Sik","family":"Hong","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi (M.L.) and Linkuo (H.-C.W.), Taiwan; Stroke Center, Geffen School of Medicine, University of California, Los Angeles, CA (J.L.S.); Department of Neurology, Ilsan Paik Hospital, Inje University, South Korea (K.-S.H.); and Department of Neurosciences, Medical University of South Carolina, Charleston, SC (B.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Chuan","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi (M.L.) and Linkuo (H.-C.W.), Taiwan; Stroke Center, Geffen School of Medicine, University of California, Los Angeles, CA (J.L.S.); Department of Neurology, Ilsan Paik Hospital, Inje University, South Korea (K.-S.H.); and Department of Neurosciences, Medical University of South Carolina, Charleston, SC (B.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Ovbiagele","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi (M.L.) and Linkuo (H.-C.W.), Taiwan; Stroke Center, Geffen School of Medicine, University of California, Los Angeles, CA (J.L.S.); Department of Neurology, Ilsan Paik Hospital, Inje University, South Korea (K.-S.H.); and Department of Neurosciences, Medical University of South Carolina, Charleston, SC (B.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.021733"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01377.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp504"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2008.09.025"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6042"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11189"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16721-4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200933"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.110.000786"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-4-200908180-00135"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(95)00134-4"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470712184"},{"key":"e_1_3_3_16_2","first-page":"719","article-title":"Statistical aspects of the analysis of data from retrospective studies of disease.","volume":"22","author":"MANTEL N","year":"1959","unstructured":"MANTEL N, HAENSZEL W. 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