aspirin and Cerebral Hemorrhage studies

Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
acetylsalicylate : A benzoate that is the conjugate base of acetylsalicylic acid, arising from deprotonation of the carboxy group.
acetylsalicylic acid : A member of the class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group. A non-steroidal anti-inflammatory drug with cyclooxygenase inhibitor activity.

Cerebral Hemorrhage: Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.

Research Excerpts

Excerpt	Relevance	Reference
"In a randomized controlled trial in Alzheimer's disease (AD), we found a higher number of intracerebral hemorrhages (ICHs) in patients randomized to aspirin treatment."	10.24	Aspirin in Alzheimer's disease: increased risk of intracerebral hemorrhage: cause for concern? ( Bentham, P; De Haan, RJ; Gray, R; Nederkoorn, PJ; Richard, E; Thoonsen, H; van Geloven, N; Van Gool, WA, 2010)
"To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin."	9.69	Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial. ( Cloud, GC; Donnan, GA; Eaton, CB; Fitzgerald, SM; Lockery, J; McNeil, JJ; Murray, AM; Nelson, MR; Newman, AB; Reid, CM; Shah, RC; Thao, LTP; Tran, C; Williamson, JD; Wolfe, R; Woods, RL, 2023)
"In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo."	9.41	Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack. ( Amarenco, P; Aunes, M; Denison, H; Evans, SR; Himmelmann, A; Jahreskog, M; James, S; Johnston, SC; Knutsson, M; Ladenvall, P; Molina, CA; Nylander, S; Röther, J; Wang, Y, 2021)
" In the AVERROES trial, we performed serial brain magnetic resonance imaging (MRI) scans in a subgroup to explore the effect of apixaban, compared with aspirin, on clinical and covert brain infarction and on microbleeds in patients with atrial fibrillation."	9.22	Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study. ( Avezum, A; Connolly, S; Dias, R; Diener, HC; Eikelboom, JW; Flaker, G; Gladstone, DJ; Hart, RG; Lewis, G; O'Donnell, MJ; Sharma, M; Smith, EE; Yusuf, S; Zhu, J, 2016)
"Dual clopidogrel-aspirin therapy was associated with a marked reduction in new strokes compared with the therapy of aspirin alone in patients with normal renal function (hazard ratio, 0."	9.22	Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack: CHANCE Substudy (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events). ( Johnston, SC; Li, H; Liu, L; Meng, X; Pan, Y; Wang, C; Wang, D; Wang, Y; Wu, Y; Zhao, X; Zhou, Y, 2016)
"We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined)."	9.20	Quality of anticoagulation control in preventing adverse events in patients with heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial substudy. ( Anker, SD; Buchsbaum, R; Di Tullio, MR; Estol, CJ; Freudenberger, RS; Graham, S; Homma, S; Labovitz, AJ; Levin, B; Lip, GY; Lok, DJ; Mann, DL; Mohr, JP; Ponikowski, P; Pullicino, PM; Qian, M; Sacco, RL; Teerlink, JR; Thompson, JL; Ye, S, 2015)
"To study whether Clopidogrel-Aspirin combined treatment for high risk transient ischaemic attack (TIA) or minor stroke results in increased number of lesions associated with anti-thrombotic cerebral haemorrhage or cerebral micro-bleeds (CMB) than aspirin alone treatment."	9.20	Combined clopidogrel-aspirin treatment for high risk TIA or minor stroke does not increase cerebral microbleeds. ( Wang, P; Wang, Y; Wang, Z; Xin, H; Xu, C, 2015)
"Ancillary analysis of the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial, comparing aspirin and apixaban, focused on sex differences."	9.19	Modification of outcomes with aspirin or apixaban in relation to female and male sex in patients with atrial fibrillation: a secondary analysis of the AVERROES study. ( Connolly, S; Eikelboom, J; Hart, RG; Lip, GY; Shestakovska, O; Yusuf, S, 2014)
"It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm."	9.16	Warfarin and aspirin in patients with heart failure and sinus rhythm. ( Ammon, SE; Anker, SD; Buchsbaum, R; del Valle, ML; Di Tullio, MR; Estol, CJ; Freudenberger, RS; Gabriel, AP; Graham, S; Homma, S; Labovitz, AJ; Levin, B; Lip, GY; Lok, DJ; Mann, DL; Massie, BM; Mejia, V; Mohr, JP; Ponikowski, P; Pullicino, PM; Sacco, RL; Sanford, AR; Teerlink, JR; Thompson, JL, 2012)
"Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy."	9.16	Bleeding during treatment with aspirin versus apixaban in patients with atrial fibrillation unsuitable for warfarin: the apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K ( Budaj, A; Connolly, SJ; Eikelboom, JW; Flaker, GC; Hart, RG; Husted, S; Kaatz, S; Lip, GY; Shestakovska, O; Yusuf, S, 2012)
"In ACTIVE-W, oral anticoagulation (OAC) was more efficacious than combined clopidogrel plus aspirin (C+A) in preventing vascular events in patients with atrial fibrillation."	9.13	Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin in patients with atrial fibrillation according to stroke risk: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE-W). ( Connolly, SJ; De Caterina, R; Flaker, G; Hart, RG; Healey, JS; Hohnloser, SH; Pfeffer, MA; Pogue, J; Yusuf, S, 2008)
"In total, 1510 patients with recent cerebral infarction (1 week to 6 months after onset) were randomly assigned to receive either sarpogrelate (100 mg TID) or aspirin (81 mg/d)."	9.13	Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A randomized, double-blind, aspirin-controlled trial. ( Fukuuchi, Y; Gotoh, F; Handa, S; Hayashi, K; Hirai, S; Kobayashi, S; Kondo, K; Nishimaru, K; Otomo, E; Sawada, T; Shinohara, Y; Terashi, A; Tohgi, H; Uchiyama, S; Yamaguchi, T, 2008)
"Most patients who have had a stroke are given aspirin; however, aspirin-related cerebral haemorrhage is a complication that is currently of concern, particularly in China where there is a high incidence of cerebral haemorrhage in secondary prevention programmes and within the community."	9.13	Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study. ( Cheng, Y; Ding, M; Fan, D; Gao, X; Hong, Z; Huang, Y; Li, Y; Li, Z; Lu, C; Wong, K; Wu, J; Xiao, J; Xu, E; Yao, C; Zeng, J; Zhang, W, 2008)
" Orbofiban, despite no significant excess risk of ICH, was not effective in preventing ischemic stroke or TIA."	9.12	Risk factors for stroke after acute coronary syndromes in the Orbofiban in Patients with Unstable Coronary Syndromes--Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study. ( Cannon, CP; Feske, SK; Murphy, S; Schwamm, LH; Smith, EE, 2006)
"We performed a combination of prespecified and exploratory subgroup analyses to detect any treatment differences among various baseline subgroups in the Warfarin-Aspirin Recurrent Stroke Study (WARSS) cohort."	9.12	Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study. ( Levin, B; Mohr, JP; Murphy, A; Prabhakaran, S; Sacco, RL; Sciacca, RR; Thompson, JL, 2006)
"While previous meta-analysis have investigated the efficacy of cilostazol in the secondary prevention of ischemic stroke, they were criticized for their methodology, which confused the acute and chronic phases of stroke."	8.90	The efficacy and safety of cilostazol for the secondary prevention of ischemic stroke in acute and chronic phases in Asian population--an updated meta-analysis. ( Chen, S; Malaguit, J; Pu, J; Shi, L; Xu, L; Zhang, J, 2014)
"Individual patient data of patients who received aspirin or placebo after cerebral ischemia were obtained from 9 clinical trials."	8.82	Risk of intracerebral hemorrhage in patients with arterial versus cardiac origin of cerebral ischemia on aspirin or placebo: analysis of individual patient data from 9 trials. ( Algra, A; Ariesen, MJ; Koudstaal, PJ; Rothwell, PM; van Walraven, C, 2004)
"In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage."	8.82	Risk of hemorrhagic stroke with aspirin use: an update. ( Gorelick, PB; Weisman, SM, 2005)
" This work aimed to explore the dynamic changes in hematoma morphology and volume in aspirin-related intracerebral hemorrhage (ARICH)."	8.31	Clinical characteristics and dynamic evaluation of hematoma morphology in patients with aspirin-related intracerebral hemorrhage. ( Huang, W; Xu, LR; Zhao, Y, 2023)
"Hematoma growth (HG) affects the prognosis of patients with spontaneous intracranial hematoma (ICH), but there is still a lack of evidence about the effects of aspirin (acetylsalicylic acid, ASA) on HG in patients with severe ICH."	8.12	Aspirin does not affect hematoma growth in severe spontaneous intracranial hematoma. ( Cao, Y; Guo, R; Jiang, P; Liu, Q; Liu, Y; Mo, S; Wang, K; Wang, S; Wu, J; Yang, J; Yang, S; Yang, Y; Zhang, J, 2022)
"Several clinical trials reported that clopidogrel was superior to aspirin in secondary stroke prevention by reducing the risk of major adverse cardiovascular events (MACE)."	7.91	Aspirin better than clopidogrel on major adverse cardiovascular events reduction after ischemic stroke: A retrospective nationwide cohort study. ( Chan, L; Chen, YC; Hsu, CY; Hu, CJ; Lin, CL; Muo, CH; Vidyanti, AN; Wu, D, 2019)
" A target for therapy might be hematoma expansion, which occurs in a significant proportion of patients, and can be exacerbated by antiplatelet medications, such as aspirin."	7.81	Aspirin Response Test role in platelet transfusion following intracerebral hemorrhage. ( Bornstein, NM; Chablani, P; Engel-Haber, E; Hammer, MD; Horev, A; Jadhav, A; Jovin, TG; Reddy, V, 2015)
"Japanese guidelines recommend aspirin 160-300 mg/day, starting within 48 h, for patients with acute cerebral infarction."	7.80	Enteric-coated aspirin versus other antiplatelet drugs in acute non-cardioembolic ischemic stroke: post-marketing study in Japan. ( Inuyama, L; Mizuno, O; Sakaguchi, T; Takahashi, S; Yamada, T, 2014)
"To analyze the potential impact of aspirin therapy for long-term secondary prevention after stroke of undetermined etiology in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH)."	7.80	Aspirin for secondary prevention after stroke of unknown etiology in resource-limited settings. ( Berkowitz, AL; Bianchi, MT; Chou, SH; Westover, MB, 2014)
"The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths."	7.79	Stroke in heart failure in sinus rhythm: the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. ( Anker, SD; Di Tullio, MR; Diek, M; Freudenberger, RS; Graham, S; Haddad, H; Homma, S; Labovitz, AJ; Lok, DJ; Mann, DL; Mohr, JP; Ponikowski, P; Pullicino, PM; Qian, M; Sacco, RL; Sanford, AR; Teerlink, JR; Thompson, JL, 2013)
"Treatment with cilostazol for 7 days before ischemia significantly suppressed the risk and severity of cerebral hemorrhage after injection of tissue-type plasminogen activator, although treatment with aspirin had no such protective effect compared with nontreated mice."	7.78	Cilostazol reduces the risk of hemorrhagic infarction after administration of tissue-type plasminogen activator in a murine stroke model. ( Kasahara, Y; Matsuyama, T; Nakagomi, T; Stern, D; Taguchi, A, 2012)
" We tested the hypothesis that combined pre-treatment with aspirin and clopidogrel is a risk factor for thrombolysis-related symptomatic intracerebral hemorrhage (sICH)."	7.75	Combined anti-platelet therapy with aspirin and clopidogrel: risk factor for thrombolysis-related intracerebral hemorrhage in acute ischemic stroke? ( Dzialowski, I; Gahn, G; Hermann, A; Koch, R, 2009)
"The relationship between nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and hemorrhagic stroke (HS) remains unclear."	7.74	Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke risk: the Acute Brain Bleeding Analysis study. ( Choi, NK; Jeong, SW; Park, BJ; Yoon, BW; Yu, KH, 2008)
"We observed poor short-term outcomes and increased mortality, probably attributable to rapid enlargement of hematomas, in the subjects with ICH who had been taking regularly moderate doses of aspirin (median 250 mg) immediately before the onset of the stroke."	7.73	Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. ( Ahonen, M; Hillbom, M; Juvela, S; Pyhtinen, J; Saloheimo, P; Savolainen, ER, 2006)
"Millions of people around the world regularly consume aspirin, but its value in determining stroke severity is still not clear."	7.73	Does prior aspirin use reduce stroke mortality? ( Demirkaya, M; Karlikaya, G; Orken, C; Tireli, H; Varlbas, F, 2006)
"The authors measured the presence and extent of asymptomatic microbleeds on gradient-recalled-echo MRI in 21 aspirin users who developed intracerebral hemorrhage and 21 aspirin users without history of intracerebral hemorrhage."	7.72	Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral hemorrhages. ( Chan, YL; Gao, S; Lam, WW; Liu, JY; Wong, KS, 2003)
"Epistaxis is a risk factor for ICH in middle-aged and elderly people, both independently and combined with the use of aspirin."	7.71	Use of aspirin, epistaxis, and untreated hypertension as risk factors for primary intracerebral hemorrhage in middle-aged and elderly people. ( Hillbom, M; Juvela, S; Saloheimo, P, 2001)
"To identify the clinical and radiologic features of intracerebral hemorrhage (ICH) in aspirin users."	7.70	Aspirin-associated intracerebral hemorrhage: clinical and radiologic features. ( Chan, YL; Kay, R; Lam, WW; Mok, V; Tang, A; Wong, KS; Woo, J, 2000)
" The objective of our study was to investigate the possible neuroprotective effects of sodium salicylate in vivo in rats with kainic acid-induced seizures, a model for temporal lobe epilepsy in human patients."	7.70	The aspirin metabolite sodium salicylate causes focal cerebral hemorrhage and cell death in rats with kainic acid-induced seizures. ( Mamelak, AN; Najbauer, J; Schuman, EM, 2000)
"Low dose Aspirin in pregnancy reduces the incidence of intra uterine growth retardation (IUGR) and pregnancy induced hypertension (PIH) in women at risk for these complications."	7.68	Low dose aspirin in pregnancy: a clinical and biochemical study of effects on the newborn. ( Foschini, M; Frusca, T; Soregaroli, M; Tarantini, M; Valcamonico, A, 1993)
"Covert brain infarcts are associated with important neurological morbidity."	7.11	Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy. ( Ameriso, SF; Bereczki, D; Berkowitz, SD; Damgaard, D; Engelter, ST; Fiebach, JB; Gagliardi, RJ; Hart, RG; Kasner, SE; Mikulik, R; Muir, KW; Mundl, H; O'Donnell, MJ; Pearce, LA; Perera, KS; Puig, J; Saad, F; Shamalov, N; Sharma, M; Shoamanesh, A; Smith, EE; Toni, DS; Veltkamp, RC; Yoon, BW, 2022)
" When used long term, aspirin has significant adverse effects and is poorly tolerated."	6.40	Use and safety of aspirin in the chemoprevention of colorectal cancer. ( Singh, AK; Trotman, BW, 1998)
"Thirty-six randomized control trials of aspirin compared with another dosage of aspirin or with placebo."	6.39	Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis. ( Cappelleri, JC; Chalmers, TC; Kupelnick, B; Lau, J, 1995)
"In a randomized controlled trial in Alzheimer's disease (AD), we found a higher number of intracerebral hemorrhages (ICHs) in patients randomized to aspirin treatment."	6.24	Aspirin in Alzheimer's disease: increased risk of intracerebral hemorrhage: cause for concern? ( Bentham, P; De Haan, RJ; Gray, R; Nederkoorn, PJ; Richard, E; Thoonsen, H; van Geloven, N; Van Gool, WA, 2010)
"To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups."	6.19	Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. ( Chen, ZM; Collins, R; Counsell, C; Liu, LS; Pan, HC; Peto, R; Sandercock, P; Warlow, C; Xie, JX, 2000)
"To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin."	5.69	Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial. ( Cloud, GC; Donnan, GA; Eaton, CB; Fitzgerald, SM; Lockery, J; McNeil, JJ; Murray, AM; Nelson, MR; Newman, AB; Reid, CM; Shah, RC; Thao, LTP; Tran, C; Williamson, JD; Wolfe, R; Woods, RL, 2023)
"Intracerebral hemorrhage was significantly increased in those with the combination of aspirin and severe hypertension (p = 0."	5.46	Reduction of intracerebral hemorrhage in hemodialysis patients after reducing aspirin use: A quality-assurance observational study. ( Antoun, L; Aoun, M; Chelala, D; Koubar, SH; Makki, M; Tamim, H, 2017)
"In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1."	5.43	Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial. ( Anker, SD; Buchsbaum, R; Di Tullio, MR; Estol, CJ; Freudenberger, RS; Graham, S; Homma, S; Labovitz, AJ; Levin, B; Lip, GY; Lok, DJ; Mann, DL; Mohr, JP; Ponikowski, P; Pullicino, PM; Qian, M; Sacco, RL; Teerlink, JR; Thompson, JL, 2016)
"In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo."	5.41	Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack. ( Amarenco, P; Aunes, M; Denison, H; Evans, SR; Himmelmann, A; Jahreskog, M; James, S; Johnston, SC; Knutsson, M; Ladenvall, P; Molina, CA; Nylander, S; Röther, J; Wang, Y, 2021)
"Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes."	5.41	Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial. ( Berkowitz, SD; Connolly, SJ; Field, TS; Hart, RG; Kasner, SE; Liu, YY; Lutsep, H; Martí-Fàbregas, J; Mikulik, R; Muir, KW; Mundl, H; Ntaios, G; O'Donnell, MJ; Olavarria, V; Santo, GC; Sharma, M; Shoamanesh, A; Smith, EE; Uchiyama, S; Veltkamp, R, 2021)
"Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS."	5.41	Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial. ( Hoshino, H; Houkin, K; Ishida, N; Isobe, M; Kimura, K; Matsumoto, M; Minematsu, K; Naritomi, H; Okada, Y; Omae, K; Origasa, H; Sakai, N; Tanaka, K; Terayama, Y; Tomimoto, H; Tominaga, T; Toyoda, K; Uchiyama, S; Yamaguchi, K; Yamaguchi, T; Yasuda, S, 2021)
"Hypertension is the most important modifiable risk factor for intracerebral hemorrhage (ICH), but blood pressure (BP) management during the acute phase of ICH is still controversial."	5.38	The effect of admission blood pressure on the prognosis of patients with intracerebral hemorrhage that occurred during treatment with aspirin, warfarin, or no drugs. ( Asil, T; Balci, K; Celik, Y; Ir, N; Tekinaslan, I; Unlu, E; Utku, U, 2012)
"Although intracerebral hemorrhage (ICH) has been described in patients with CADASIL, the cause of such ICH is still unknown."	5.35	Aspirin-associated intracerebral hemorrhage in a patient with CADASIL. ( Choi, JC; Kang, JH; Kang, SY; Lee, JS; Oh, JH, 2008)
"(2) Aspirin has been tested in several placebo-controlled trials and has a positive risk-benefit balance, preventing about 5 deaths per 1000 patients with ischaemic stroke."	5.33	Ischaemic stroke: acute-phase drug therapy. Mostly aspirin and heparin. ( , 2005)
"In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke."	5.27	Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial. ( Ahn, SH; Heo, SH; Hong, KS; Hwang, YH; Jung, JM; Kang, DW; Kim, BJ; Kim, YJ; Kwon, JH; Kwon, SU; Lee, EJ; Lee, J; Lee, JH; Lee, JS; Navarro, JC; Park, JH; Park, JM; Rha, JH; Seo, WK; Sohn, SI; Wong, LKS; Yu, S, 2018)
" In the AVERROES trial, we performed serial brain magnetic resonance imaging (MRI) scans in a subgroup to explore the effect of apixaban, compared with aspirin, on clinical and covert brain infarction and on microbleeds in patients with atrial fibrillation."	5.22	Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study. ( Avezum, A; Connolly, S; Dias, R; Diener, HC; Eikelboom, JW; Flaker, G; Gladstone, DJ; Hart, RG; Lewis, G; O'Donnell, MJ; Sharma, M; Smith, EE; Yusuf, S; Zhu, J, 2016)
"Dual clopidogrel-aspirin therapy was associated with a marked reduction in new strokes compared with the therapy of aspirin alone in patients with normal renal function (hazard ratio, 0."	5.22	Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack: CHANCE Substudy (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events). ( Johnston, SC; Li, H; Liu, L; Meng, X; Pan, Y; Wang, C; Wang, D; Wang, Y; Wu, Y; Zhao, X; Zhou, Y, 2016)
"We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined)."	5.20	Quality of anticoagulation control in preventing adverse events in patients with heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial substudy. ( Anker, SD; Buchsbaum, R; Di Tullio, MR; Estol, CJ; Freudenberger, RS; Graham, S; Homma, S; Labovitz, AJ; Levin, B; Lip, GY; Lok, DJ; Mann, DL; Mohr, JP; Ponikowski, P; Pullicino, PM; Qian, M; Sacco, RL; Teerlink, JR; Thompson, JL; Ye, S, 2015)
"PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage was designed to compare cilostazol and aspirin and to assess the effect of adding probucol, a lipid-lowering and anti-oxidative agent, in patients at high risk of haemorrhagic stroke."	5.20	Rationale and design of the PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO) study: A randomized controlled trial. ( Hong, KS; Kim, BJ; Kwon, SU; Lee, JY, 2015)
"To study whether Clopidogrel-Aspirin combined treatment for high risk transient ischaemic attack (TIA) or minor stroke results in increased number of lesions associated with anti-thrombotic cerebral haemorrhage or cerebral micro-bleeds (CMB) than aspirin alone treatment."	5.20	Combined clopidogrel-aspirin treatment for high risk TIA or minor stroke does not increase cerebral microbleeds. ( Wang, P; Wang, Y; Wang, Z; Xin, H; Xu, C, 2015)
"Ancillary analysis of the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial, comparing aspirin and apixaban, focused on sex differences."	5.19	Modification of outcomes with aspirin or apixaban in relation to female and male sex in patients with atrial fibrillation: a secondary analysis of the AVERROES study. ( Connolly, S; Eikelboom, J; Hart, RG; Lip, GY; Shestakovska, O; Yusuf, S, 2014)
"We identified 9 independent risk factors for SICH: baseline National Institutes of Health Stroke Scale, serum glucose, systolic blood pressure, age, body weight, stroke onset to treatment time, aspirin or combined aspirin and clopidogrel, and history of hypertension."	5.16	Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score. ( Ahmed, N; Egido, JA; Ford, GA; Lees, KR; Mazya, M; Mikulik, R; Toni, D; Wahlgren, N, 2012)
"We analyzed MRI of 133 patients admitted consecutively for intra- and extracranial stenting for symptomatic large artery atherosclerosis who received aspirin and clopidogrel."	5.16	Risk of intracerebral hemorrhage in patients with cerebral microbleeds undergoing endovascular intervention. ( Abrigo, J; Ahuja, AT; Leung, TW; Ng, N; Siu, DY; Soo, YO; Wong, LK; Yu, S, 2012)
"It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm."	5.16	Warfarin and aspirin in patients with heart failure and sinus rhythm. ( Ammon, SE; Anker, SD; Buchsbaum, R; del Valle, ML; Di Tullio, MR; Estol, CJ; Freudenberger, RS; Gabriel, AP; Graham, S; Homma, S; Labovitz, AJ; Levin, B; Lip, GY; Lok, DJ; Mann, DL; Massie, BM; Mejia, V; Mohr, JP; Ponikowski, P; Pullicino, PM; Sacco, RL; Sanford, AR; Teerlink, JR; Thompson, JL, 2012)
"Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy."	5.16	Bleeding during treatment with aspirin versus apixaban in patients with atrial fibrillation unsuitable for warfarin: the apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K ( Budaj, A; Connolly, SJ; Eikelboom, JW; Flaker, GC; Hart, RG; Husted, S; Kaatz, S; Lip, GY; Shestakovska, O; Yusuf, S, 2012)
"TAIST was a randomized controlled trial assessing 10 days of treatment with tinzaparin versus aspirin in 1489 patients with acute ischemic stroke (<48 hr) with admission BP of	5.14	The relationship between baseline blood pressure and computed tomography findings in acute stroke: data from the tinzaparin in acute ischaemic stroke trial (TAIST). ( Bath, PM; Christensen, H; De Deyn, PP; England, T; Geeganage, C; Gray, LJ; Leys, D; Moulin, T; O'Neill, D; Ringelstein, EB; Sare, GM; Woimant, F, 2009)
"The analyses used data from the Tinzapararin in Acute Ischaemic Stroke Trial, a randomized controlled trial assessing tinzaparin (low molecular weight heparin) versus aspirin in 1484 patients with acute ischemic stroke."	5.14	Asymptomatic hemorrhagic transformation of infarction and its relationship with functional outcome and stroke subtype: assessment from the Tinzaparin in Acute Ischaemic Stroke Trial. ( Bath, PM; Christensen, H; De Deyn, P; England, TJ; Geeganage, C; Leys, D; Moulin, T; O'Neill, D; Ringelstein, EB; Sare, GM; Woimant, F, 2010)
"We extended the follow-up of 2473 patients from the Dutch TIA Trial (recruitment March 1986 to March 1989, all treated with aspirin; CIAO) and 186 Dutch participants of the European Atrial Fibrillation Trial (recruitment June 1988 to May 1992, 26% on anticoagulants during the trial; CIAF)."	5.13	Long-term occurrence of death and cardiovascular events in patients with transient ischaemic attack or minor ischaemic stroke: comparison between arterial and cardiac source of the index event. ( Algra, A; Gorter, JW; Kappelle, LJ; Koudstaal, PJ; van Gijn, J; van Wijk, I, 2008)
"In ACTIVE-W, oral anticoagulation (OAC) was more efficacious than combined clopidogrel plus aspirin (C+A) in preventing vascular events in patients with atrial fibrillation."	5.13	Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin in patients with atrial fibrillation according to stroke risk: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE-W). ( Connolly, SJ; De Caterina, R; Flaker, G; Hart, RG; Healey, JS; Hohnloser, SH; Pfeffer, MA; Pogue, J; Yusuf, S, 2008)
"In total, 1510 patients with recent cerebral infarction (1 week to 6 months after onset) were randomly assigned to receive either sarpogrelate (100 mg TID) or aspirin (81 mg/d)."	5.13	Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A randomized, double-blind, aspirin-controlled trial. ( Fukuuchi, Y; Gotoh, F; Handa, S; Hayashi, K; Hirai, S; Kobayashi, S; Kondo, K; Nishimaru, K; Otomo, E; Sawada, T; Shinohara, Y; Terashi, A; Tohgi, H; Uchiyama, S; Yamaguchi, T, 2008)
"Most patients who have had a stroke are given aspirin; however, aspirin-related cerebral haemorrhage is a complication that is currently of concern, particularly in China where there is a high incidence of cerebral haemorrhage in secondary prevention programmes and within the community."	5.13	Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study. ( Cheng, Y; Ding, M; Fan, D; Gao, X; Hong, Z; Huang, Y; Li, Y; Li, Z; Lu, C; Wong, K; Wu, J; Xiao, J; Xu, E; Yao, C; Zeng, J; Zhang, W, 2008)
" Orbofiban, despite no significant excess risk of ICH, was not effective in preventing ischemic stroke or TIA."	5.12	Risk factors for stroke after acute coronary syndromes in the Orbofiban in Patients with Unstable Coronary Syndromes--Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study. ( Cannon, CP; Feske, SK; Murphy, S; Schwamm, LH; Smith, EE, 2006)
"We performed a combination of prespecified and exploratory subgroup analyses to detect any treatment differences among various baseline subgroups in the Warfarin-Aspirin Recurrent Stroke Study (WARSS) cohort."	5.12	Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study. ( Levin, B; Mohr, JP; Murphy, A; Prabhakaran, S; Sacco, RL; Sciacca, RR; Thompson, JL, 2006)
"Immediately after TIA or minor stroke, patients are at high risk of stroke, which might be reduced by using clopidogrel in addition to aspirin."	5.12	Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. ( Buchan, AM; Demchuk, AM; Eliasziw, M; Hill, MD; Kennedy, J; Ryckborst, KJ, 2007)
"In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0."	4.90	Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis. ( Arrich, J; Gouya, G; Gurbel, PA; Huber, K; Pirker-Kees, A; Siller-Matula, JM; Verheugt, FW; Wolzt, M, 2014)
"While previous meta-analysis have investigated the efficacy of cilostazol in the secondary prevention of ischemic stroke, they were criticized for their methodology, which confused the acute and chronic phases of stroke."	4.90	The efficacy and safety of cilostazol for the secondary prevention of ischemic stroke in acute and chronic phases in Asian population--an updated meta-analysis. ( Chen, S; Malaguit, J; Pu, J; Shi, L; Xu, L; Zhang, J, 2014)
" Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1."	4.88	Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials. ( Benavente, OR; Hart, RG; Palacio, S; Pearce, LA, 2012)
" Increasing independent survival by even a small proportion through early use of aspirin in the majority with ischaemic stroke, avoiding aspirin in those with haemorrhagic stroke, and appropriate early management of those who have not had a stroke, reduced costs and increased QALYs."	4.82	What is the best imaging strategy for acute stroke? ( Cairns, J; Dennis, MS; Keir, SL; Lewis, S; Sandercock, PA; Seymour, J; Wardlaw, JM, 2004)
"Individual patient data of patients who received aspirin or placebo after cerebral ischemia were obtained from 9 clinical trials."	4.82	Risk of intracerebral hemorrhage in patients with arterial versus cardiac origin of cerebral ischemia on aspirin or placebo: analysis of individual patient data from 9 trials. ( Algra, A; Ariesen, MJ; Koudstaal, PJ; Rothwell, PM; van Walraven, C, 2004)
"In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage."	4.82	Risk of hemorrhagic stroke with aspirin use: an update. ( Gorelick, PB; Weisman, SM, 2005)
"Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke."	4.80	Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. ( He, J; Klag, MJ; Vu, B; Whelton, PK, 1998)
"Our study aimed to explore the effectiveness and safety of intravenous t-PA compared with dual antiplatelet therapy (DAPT) and aspirin alone for minor stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤5 and large vessel occlusion (LVO)."	4.31	Intravenous thrombolysis versus antiplatelet therapy in minor stroke patients with large vessel occlusion. ( Duan, C; Feng, X; Gu, H; Hao, M; Meng, X; Wang, S; Wang, Y; Xiong, Y; Yang, KX; Zhao, X, 2023)
"Aspirin is widely used as secondary prophylaxis for acute ischemic stroke."	4.31	In-Hospital Aspirin Dose as a Risk Factor for Hemorrhagic Transformation in Patients Not Treated With Thrombolysis. ( Clares de Andrade, JB; de Abreu, GQ; de Carvalho, JJF; Lima, FO; Maia Barros, LC; Mohr, JP; Pontes-Neto, OM; Silva, GS, 2023)
" This work aimed to explore the dynamic changes in hematoma morphology and volume in aspirin-related intracerebral hemorrhage (ARICH)."	4.31	Clinical characteristics and dynamic evaluation of hematoma morphology in patients with aspirin-related intracerebral hemorrhage. ( Huang, W; Xu, LR; Zhao, Y, 2023)
"Hematoma growth (HG) affects the prognosis of patients with spontaneous intracranial hematoma (ICH), but there is still a lack of evidence about the effects of aspirin (acetylsalicylic acid, ASA) on HG in patients with severe ICH."	4.12	Aspirin does not affect hematoma growth in severe spontaneous intracranial hematoma. ( Cao, Y; Guo, R; Jiang, P; Liu, Q; Liu, Y; Mo, S; Wang, K; Wang, S; Wu, J; Yang, J; Yang, S; Yang, Y; Zhang, J, 2022)
"In patients with acute intracerebral hemorrhage, hematoma appearances on CT are associated with biomarkers of platelet activity and clopidogrel use prior to admission."	4.12	Antiplatelet Medications and Biomarkers of Hemostasis May Explain the Association of Hematoma Appearance and Subsequent Hematoma Expansion After Intracerebral Hemorrhage. ( Kwaan, H; Lindholm, PF; Luo, Y; Metcalf-Doetsch, W; Naidech, AM; Shin, HJ; Tang, M, 2022)
"Several clinical trials reported that clopidogrel was superior to aspirin in secondary stroke prevention by reducing the risk of major adverse cardiovascular events (MACE)."	3.91	Aspirin better than clopidogrel on major adverse cardiovascular events reduction after ischemic stroke: A retrospective nationwide cohort study. ( Chan, L; Chen, YC; Hsu, CY; Hu, CJ; Lin, CL; Muo, CH; Vidyanti, AN; Wu, D, 2019)
" After multivariate logistic regression, 10 variables remained independent predictors of sICH to compose the STARTING-SICH (systolic blood pressure, age, onset-to-treatment time for thrombolysis, National Institutes of Health Stroke Scale score, glucose, aspirin alone, aspirin plus clopidogrel, anticoagulant with INR ≤1."	3.88	STARTING-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis for Stroke. ( Bonetti, B; Bovi, P; Cappellari, M; Forlivesi, S; Toni, D; Turcato, G; Zivelonghi, C, 2018)
"We used nationwide population-based registries to identify all first-time hospitalizations for stroke and subsequent mortality in patients treated with aspirin and clopidogrel in Denmark during 2004-2012."	3.88	Pre-admission use of platelet inhibitors and short-term stroke mortality: a population-based cohort study. ( Christiansen, CF; Grove, EL; Henderson, VW; Horváth-Puhó, E; Schmidt, M; Sørensen, HT; Würtz, M, 2018)
" A target for therapy might be hematoma expansion, which occurs in a significant proportion of patients, and can be exacerbated by antiplatelet medications, such as aspirin."	3.81	Aspirin Response Test role in platelet transfusion following intracerebral hemorrhage. ( Bornstein, NM; Chablani, P; Engel-Haber, E; Hammer, MD; Horev, A; Jadhav, A; Jovin, TG; Reddy, V, 2015)
"In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke."	3.81	Comparison of antiplatelet regimens in secondary stroke prevention: a nationwide cohort study. ( Carlson, N; Christiansen, CB; Gerds, TA; Gislason, G; Jørgensen, ME; Kristensen, SL; Numé, AK; Olesen, JB; Pallisgaard, J; Torp-Pedersen, C, 2015)
"Japanese guidelines recommend aspirin 160-300 mg/day, starting within 48 h, for patients with acute cerebral infarction."	3.80	Enteric-coated aspirin versus other antiplatelet drugs in acute non-cardioembolic ischemic stroke: post-marketing study in Japan. ( Inuyama, L; Mizuno, O; Sakaguchi, T; Takahashi, S; Yamada, T, 2014)
"To analyze the potential impact of aspirin therapy for long-term secondary prevention after stroke of undetermined etiology in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH)."	3.80	Aspirin for secondary prevention after stroke of unknown etiology in resource-limited settings. ( Berkowitz, AL; Bianchi, MT; Chou, SH; Westover, MB, 2014)
"The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths."	3.79	Stroke in heart failure in sinus rhythm: the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. ( Anker, SD; Di Tullio, MR; Diek, M; Freudenberger, RS; Graham, S; Haddad, H; Homma, S; Labovitz, AJ; Lok, DJ; Mann, DL; Mohr, JP; Ponikowski, P; Pullicino, PM; Qian, M; Sacco, RL; Sanford, AR; Teerlink, JR; Thompson, JL, 2013)
"Treatment with cilostazol for 7 days before ischemia significantly suppressed the risk and severity of cerebral hemorrhage after injection of tissue-type plasminogen activator, although treatment with aspirin had no such protective effect compared with nontreated mice."	3.78	Cilostazol reduces the risk of hemorrhagic infarction after administration of tissue-type plasminogen activator in a murine stroke model. ( Kasahara, Y; Matsuyama, T; Nakagomi, T; Stern, D; Taguchi, A, 2012)
"There was a clear impact of aspirin treatment on CMBs associated with intracerebral hemorrhage in Chinese patients."	3.77	Aspirin treatment increases the risk of cerebral microbleeds. ( Gao, Y; Ge, L; Guo, D; Han, X; Niu, G; Wu, H; Wu, Q; Zhang, Y, 2011)
" We tested the hypothesis that combined pre-treatment with aspirin and clopidogrel is a risk factor for thrombolysis-related symptomatic intracerebral hemorrhage (sICH)."	3.75	Combined anti-platelet therapy with aspirin and clopidogrel: risk factor for thrombolysis-related intracerebral hemorrhage in acute ischemic stroke? ( Dzialowski, I; Gahn, G; Hermann, A; Koch, R, 2009)
"The relationship between nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and hemorrhagic stroke (HS) remains unclear."	3.74	Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke risk: the Acute Brain Bleeding Analysis study. ( Choi, NK; Jeong, SW; Park, BJ; Yoon, BW; Yu, KH, 2008)
"We observed poor short-term outcomes and increased mortality, probably attributable to rapid enlargement of hematomas, in the subjects with ICH who had been taking regularly moderate doses of aspirin (median 250 mg) immediately before the onset of the stroke."	3.73	Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. ( Ahonen, M; Hillbom, M; Juvela, S; Pyhtinen, J; Saloheimo, P; Savolainen, ER, 2006)
"Millions of people around the world regularly consume aspirin, but its value in determining stroke severity is still not clear."	3.73	Does prior aspirin use reduce stroke mortality? ( Demirkaya, M; Karlikaya, G; Orken, C; Tireli, H; Varlbas, F, 2006)
"The authors measured the presence and extent of asymptomatic microbleeds on gradient-recalled-echo MRI in 21 aspirin users who developed intracerebral hemorrhage and 21 aspirin users without history of intracerebral hemorrhage."	3.72	Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral hemorrhages. ( Chan, YL; Gao, S; Lam, WW; Liu, JY; Wong, KS, 2003)
"Warfarin increases both the likelihood and the mortality of intracerebral hemorrhage (ICH), particularly in patients with a history of prior ICH."	3.72	Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. ( Eckman, MH; Greenberg, SM; Knudsen, KA; Rosand, J; Singer, DE, 2003)
"Epistaxis is a risk factor for ICH in middle-aged and elderly people, both independently and combined with the use of aspirin."	3.71	Use of aspirin, epistaxis, and untreated hypertension as risk factors for primary intracerebral hemorrhage in middle-aged and elderly people. ( Hillbom, M; Juvela, S; Saloheimo, P, 2001)
" The findings also suggest that older patients and those who have used aspirin before stroke are at higher risk of a severe HT on rtPA."	3.71	Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). ( Bluhmki, E; Larrue, V; Müller, A; von Kummer R, R, 2001)
" He received 325 mg of aspirin daily for at least 6 years, suffered an AMI, and was successfully reperfused with alteplase, but after 44 hours developed a large hemorrhagic stroke resulting in paraplegia."	3.70	Depressed platelet status in an elderly patient with hemorrhagic stroke after thrombolysis for acute myocardial infarction. GUSTO-III Investigators. ( Bahr, RD; Dalesandro, MR; Grabletz, LB; Gumbs, CI; Gurbel, PA; Ohman, EM; Serebruany, VL; Shustov, AR; Topol, EJ, 1998)
"To identify the clinical and radiologic features of intracerebral hemorrhage (ICH) in aspirin users."	3.70	Aspirin-associated intracerebral hemorrhage: clinical and radiologic features. ( Chan, YL; Kay, R; Lam, WW; Mok, V; Tang, A; Wong, KS; Woo, J, 2000)
" The objective of our study was to investigate the possible neuroprotective effects of sodium salicylate in vivo in rats with kainic acid-induced seizures, a model for temporal lobe epilepsy in human patients."	3.70	The aspirin metabolite sodium salicylate causes focal cerebral hemorrhage and cell death in rats with kainic acid-induced seizures. ( Mamelak, AN; Najbauer, J; Schuman, EM, 2000)
"Low dose Aspirin in pregnancy reduces the incidence of intra uterine growth retardation (IUGR) and pregnancy induced hypertension (PIH) in women at risk for these complications."	3.68	Low dose aspirin in pregnancy: a clinical and biochemical study of effects on the newborn. ( Foschini, M; Frusca, T; Soregaroli, M; Tarantini, M; Valcamonico, A, 1993)
"We studied the incidence of cerebral hemorrhage in an animal model of embolic stroke to determine the safety of aspirin, heparin, and tissue plasminogen activator therapies."	3.68	Cerebral hemorrhagic risk of aspirin or heparin therapy with thrombolytic treatment in rabbits. ( Clark, WM; Lyden, PD; Madden, KP; Zivin, JA, 1991)
" On day 2 post partum, mothers were questioned regarding maternal risk factors, including the use of either aspirin or acetaminophen during the last week of pregnancy."	3.66	Neonatal intracranial hemorrhage and maternal use of aspirin. ( Braithwaite, WR; Guggenheim, MA; Johnson, ML; Peterson, RG; Rumack, BH; Rumack, CM, 1981)
"Among patients with minor nondisabling acute ischemic stroke presenting within 4."	3.30	Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial. ( Chen, HS; Cui, Y; Dong, YL; Guo, LY; Han, J; Huang, SM; Jiang, CH; Li, J; Li, JY; Li, YS; Li, Z; Lin, YZ; Lu, J; Ma, GB; Nguyen, TN; Piao, XY; Shen, LY; Wan, LS; Wang, DL; Wang, EQ; Wang, J; Wang, LX; Wang, RX; Wang, WZ; Xia, L; Yang, KH; Yang, QC; Zhang, H; Zhang, L; Zhou, ZH, 2023)
"Covert brain infarcts are associated with important neurological morbidity."	3.11	Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy. ( Ameriso, SF; Bereczki, D; Berkowitz, SD; Damgaard, D; Engelter, ST; Fiebach, JB; Gagliardi, RJ; Hart, RG; Kasner, SE; Mikulik, R; Muir, KW; Mundl, H; O'Donnell, MJ; Pearce, LA; Perera, KS; Puig, J; Saad, F; Shamalov, N; Sharma, M; Shoamanesh, A; Smith, EE; Toni, DS; Veltkamp, RC; Yoon, BW, 2022)
"Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies."	2.84	Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment interactions. ( Anderson, DC; Bazan, C; Benavente, OR; Catanese, L; Hart, RG; Kase, CS; Marti-Fabregas, J; McClure, LA; Pearce, LA; Sharma, M; Shoamanesh, A, 2017)
"Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3."	2.74	Bleeding increases the risk of ischemic events in patients with peripheral arterial disease. ( Algra, A; Eikelboom, BC; Lawson, JA; Moll, FL; Tangelder, MJ; van Hattum, ES, 2009)
"The term embolic stroke of undetermined source (ESUS) was coined to describe ischemic strokes in which the radiographic features demonstrate territorial infarcts resembling those seen in patients with confirmed sources of embolism but without a clear source of embolism detected."	2.72	Reexamination of the Embolic Stroke of Undetermined Source Concept. ( Albers, GW; Bernstein, R; Brachmann, J; Camm, AJ; Fromm, P; Goto, S; Granger, CB; Hohnloser, SH; Hylek, E; Kowey, P; Krieger, D; Passman, R; Pines, JM, 2021)
"Aspirin use at entry was also associated with a 4-fold (95% CI, 1."	2.69	Aspirin use and incident stroke in the cardiovascular health study. CHS Collaborative Research Group. ( Beauchamp, NJ; Hart, RG; Kronmal, RA; Manolio, TA; Newman, A; Talbert, RL, 1998)
"Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed."	2.69	Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators. ( Alberts, MJ; Berdan, LG; Califf, RM; Deckers, J; Graffagnino, C; Granger, CB; Harrington, RA; Laskowitz, DT; Lincoff, AM; MacAulay, CM; Mahaffey, KW; Miller, JM; Simoons, ML; Sloan, MA; Topol, EJ, 1999)
"Patients with 50 to 99% stenosis of an intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or basilar) were identified by reviewing the results of consecutive angiograms performed at participating centers between 1985 and 1991."	2.68	The Warfarin-Aspirin Symptomatic Intracranial Disease Study. ( Brown, MB; Chimowitz, MI; Furlan, AJ; Kokkinos, J; Levine, SR; Pessin, MS; Sila, CA; Silliman, S; Strong, J; Weichel, E, 1995)
" This paper reviews the pattern of adverse reactions to AAS and their relationship to the dosage of ASS evaluated."	2.68	[Secondary prevention of ischemic strokes: effect of dosage of aspirin]. ( Alvarez-Sabín, J; Calvo, G; Morros, R, 1997)
"Various strategies are emerging for dosing antiplatelet therapies in preparation for pipeline stent embolization in adults."	2.55	Optimal pediatric dosing of anti-platelet agents for pipeline stent embolization -a case report and review of the literature. ( Cobb, MIH; Fernando Gonzalez, L; Hauck, EF; Smith, TP; Zomorodi, AR, 2017)
"Performance in patients with cerebral ischemia was poor."	2.53	Prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy: a systematic review and external validation study. ( Algra, A; Greving, JP; Hilkens, NA, 2016)
"The authors present a case of delayed acute subdural hematoma and review all reported cases in the literature."	2.53	Case Report and Review of Literature of Delayed Acute Subdural Hematoma. ( Baisden, JL; Doan, N; Nguyen, HS; Shabani, S, 2016)
"Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear."	2.49	Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials. ( Clarke, A; Connock, M; Freeman, K; Grove, A; Gurung, B; Gurung, T; Johnson, S; Morrow, S; Ngianga-Bakwin, K; Stranges, S; Sutcliffe, P, 2013)
" In addition, the discussion here reviews select acute ischemic stroke intravenous thrombolytic studies, such as the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study and European Cooperative Acute Stroke Studies, select neuroprotectant and endovascular clot retrieval device studies, and large cooperative databases, such as the Virtual International Stroke Trials Archive and Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry, to explore relationships between baseline stroke severity and other possible factors associated with efficacy and safety outcomes."	2.48	How baseline severity affects efficacy and safety outcomes in acute ischemic stroke intervention trials. ( Gorelick, PB, 2012)
"In acute intracerebral hemorrhage the beneficial effect of recombinant coagulation factor VII found in a small study could not be proved in a large phase III trial."	2.45	[Pharmacotherapy of stroke]. ( Bereczki, D, 2009)
"Approximately 7000 intracerebral hemorrhages (ICHs) annually in the US are caused by use of antithrombotic therapies."	2.43	Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. ( Hart, RG; Pearce, LA; Tonarelli, SB, 2005)
"Fibrinolysis is the reference treatment for most myocardial infarctions with ST-segment elevation; alternatives are angioplasty, with or without stent."	2.43	New anticoagulants in ischemic heart disease. ( Verheugt, FW, 2005)
"Hypertension that complicates preeclampsia in pregnancy is a disorder that requires special consideration in both prevention and pharmacologic treatment."	2.43	Pathophysiology and medical management of systemic hypertension in preeclampsia. ( Frishman, WH; Schlocker, SJ; Tejani, N; Veresh, M, 2006)
"Aspirin has an essential place formally demonstrated in ISIS 2."	2.41	[Fibrinolysis in myocardial infarction with EKG elevation. Optimization of myocardial reperfusion by treatment with antithrombotic agents]. ( Coste, P; Jaïs, C; Labèque, JN; Lafitte, S; Perron, JM; Roudaut, R; Zabsonré, P, 2001)
" When used long term, aspirin has significant adverse effects and is poorly tolerated."	2.40	Use and safety of aspirin in the chemoprevention of colorectal cancer. ( Singh, AK; Trotman, BW, 1998)
"Thirty-six randomized control trials of aspirin compared with another dosage of aspirin or with placebo."	2.39	Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis. ( Cappelleri, JC; Chalmers, TC; Kupelnick, B; Lau, J, 1995)
"Spontaneous (nontraumatic) intracerebral hemorrhage (ICH) is the most severe complication of antithrombotic drug use."	1.62	Trends in Incidence of Intracerebral Hemorrhage and Association With Antithrombotic Drug Use in Denmark, 2005-2018. ( Al-Shahi Salman, R; Christensen, H; Gaist, D; García Rodríguez, LA; Hald, SM; Hallas, J; Hellfritzsch, M; Möller, S; Pottegård, A; Sharma, M, 2021)
"Antiplatelet use on the risk of intracerebral hemorrhage (ICH) in patients with Alzheimer's disease (AD) has not yet been completely elucidated."	1.56	The Impact of Antiplatelet Use on the Risk of Intracerebral Hemorrhage in Patients with Alzheimer's Disease: A Nationwide Cohort Study. ( Chang, YM; Chen, CH; Chien, CY; Lee, TL; Lin, SH; Lin, TY; Liu, CH; Sung, PS; Tsai, KJ, 2020)
"Among those developing intracranial hemorrhage, limited data are available to guide clinicians with antithrombotic reinitiation."	1.56	Warfarin Reinitiation After Intracranial Hemorrhage: A Case Series of Heart Valve Patients. ( Bungard, TJ; Butcher, K; Hodgson, M; Schultz, K; Wan, A, 2020)
" We used femtosecond laser ablation to rupture arterioles in the cortex of both young (2-5 months old) and aged (18-29 months old) mice dosed on aspirin in their drinking water and measured the extent of penetration of both red blood cells and blood plasma into the surrounding tissue."	1.51	Aspirin treatment does not increase microhemorrhage size in young or aged mice. ( Brophy, M; Chan, S; Nishimura, N; Schaffer, CB, 2019)
"The WMHs and MB were associated with CMBs in patients taking aspirin or clopidogrel for >1 year, and long-term use increased the risks of CMB and bleeding."	1.51	Cerebral microbleeds in patients with ischemic cerebrovascular disease taking aspirin or clopidogrel. ( Ban, C; Ge, L; Liang, J; Ouyang, X; Wu, H; Wu, Q; Yu, H, 2019)
"Post-LVAD strokes are an important cause of morbidity and reduced quality of life."	1.48	Cerebrovascular Accidents During Mechanical Circulatory Support: New Predictors of Ischemic and Hemorrhagic Strokes and Outcome. ( Ahmed, FS; Akbik, F; Feske, SK; Givertz, MM; Izzy, S; Renault, S; Rubin, DB; Smallwood, JA; Sylvester, KW; Vaitkevicius, H, 2018)
"Intracerebral hemorrhage was significantly increased in those with the combination of aspirin and severe hypertension (p = 0."	1.46	Reduction of intracerebral hemorrhage in hemodialysis patients after reducing aspirin use: A quality-assurance observational study. ( Antoun, L; Aoun, M; Chelala, D; Koubar, SH; Makki, M; Tamim, H, 2017)
" No duration of use or dose-response association was apparent."	1.46	Low-dose aspirin and risk of intracranial bleeds: An observational study in UK general practice. ( Bromley, S; Cea Soriano, L; Gaist, D; García Rodríguez, LA; Soriano-Gabarró, M, 2017)
"In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted hazard ratio, 1."	1.43	Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial. ( Anker, SD; Buchsbaum, R; Di Tullio, MR; Estol, CJ; Freudenberger, RS; Graham, S; Homma, S; Labovitz, AJ; Levin, B; Lip, GY; Lok, DJ; Mann, DL; Mohr, JP; Ponikowski, P; Pullicino, PM; Qian, M; Sacco, RL; Teerlink, JR; Thompson, JL, 2016)
"Aspirin (53."	1.43	Antithrombotic Medication Use and Misuse Among Patients with Intracranial Hemorrhage: A 16-Year, Lebanese, Single-Center Experience. ( Fahed, E; Ghauche, J; Maarrawi, J; Menassa-Moussa, L; Moussa, R; Nohra, G; Okais, N; Rahme, R; Rizk, T; Samaha, E, 2016)
" All patients received low-molecular-weight heparin in prophylactic dosage starting 24 hours after aneurysm treatment."	1.42	Ventriculostomy-Related Hemorrhage After Treatment of Acutely Ruptured Aneurysms: The Influence of Anticoagulation and Antiplatelet Treatment. ( Bruder, M; El-Fiki, A; Güresir, E; Konczalla, J; Lescher, S; Schuss, P; Seifert, V; Vatter, H, 2015)
"Patients with a history of cerebral hemorrhage were excluded."	1.40	Associations of durations of antiplatelet use and vascular risk factors with the presence of cerebral microbleeds. ( Hattori, N; Okuma, Y; Tanaka, R; Tanaka, Y; Ueno, Y; Urabe, T; Yamashiro, K, 2014)
"We sought to determine the prevalence of acute respiratory distress syndrome after intracerebral hemorrhage, characterize risk factors for its development, and assess its impact on patient outcomes."	1.39	Acute respiratory distress syndrome after spontaneous intracerebral hemorrhage*. ( Avery, L; Bajwa, E; Camargo, CA; Chang, Y; Duran-Mendicuti, MA; Elmer, J; Goldstein, JN; Greenberg, SM; Hess, DR; Hou, P; Okechukwu, I; Pallin, DJ; Pontes-Neto, O; Rosand, J; Schreiber, H; Wilcox, SR, 2013)
"Hypertension is the most important modifiable risk factor for intracerebral hemorrhage (ICH), but blood pressure (BP) management during the acute phase of ICH is still controversial."	1.38	The effect of admission blood pressure on the prognosis of patients with intracerebral hemorrhage that occurred during treatment with aspirin, warfarin, or no drugs. ( Asil, T; Balci, K; Celik, Y; Ir, N; Tekinaslan, I; Unlu, E; Utku, U, 2012)
"Delayed intracerebral hemorrhage (DIH) was observed more often in the routine antiplatelet group (2/9 cases, 22."	1.37	Delayed intracranial hemorrhage associated with antiplatelet therapy in stent-assisted coil embolized cerebral aneurysms. ( Chai, WN; He, ZH; Sun, XC; Wu, HT; Zhang, XD; Zhu, J, 2011)
"Cilostazol is an antiplatelet drug often used in Asia; however, it is rarely used in the western hemisphere, particularly for stroke patients."	1.37	Cilostazol: a drug particularly effective for Asians? ( Kim, JS; Shinohara, Y, 2011)
"We assessed the safety of thrombolysis under APs in 11,865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR)."	1.36	Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset. ( Ahmed, N; Diedler, J; Ford, GA; Lees, KR; Luijckx, GJ; Overgaard, K; Ringleb, P; Soinne, L; Sykora, M; Uyttenboogaart, M; Wahlgren, N, 2010)
"The underlying disease was paroxysmal nocturnal hemoglobinuria (PNH), a stem cell defect characterized by episodes of complement-induced hemolysis and thromboembolic events."	1.36	[Between thrombosis and bleeding - a case of paroxysmal nocturnal hemoglobinuria]. ( Reinhart, WH, 2010)
"Although intracerebral hemorrhage (ICH) has been described in patients with CADASIL, the cause of such ICH is still unknown."	1.35	Aspirin-associated intracerebral hemorrhage in a patient with CADASIL. ( Choi, JC; Kang, JH; Kang, SY; Lee, JS; Oh, JH, 2008)
"Aspirin was not associated with increased early mortality."	1.35	Effect of aspirin and warfarin on early survival after intracerebral haemorrhage. ( Brown, AJ; Fletcher, VJ; Frampton, CM; Hanger, HC; Sainsbury, R; Wilkinson, TJ, 2008)
"(2) Aspirin has been tested in several placebo-controlled trials and has a positive risk-benefit balance, preventing about 5 deaths per 1000 patients with ischaemic stroke."	1.33	Ischaemic stroke: acute-phase drug therapy. Mostly aspirin and heparin. ( , 2005)
"Two hundred and sixty-one cerebral aneurysms were treated in 247 patients by endovascular coil embolization from January 2001 to September 2004."	1.33	Intravenous administration of acetylsalicylic acid during endovascular treatment of cerebral aneurysms reduces the rate of thromboembolic events. ( Buhk, JH; Fiehler, J; Goebell, E; Grzyska, U; Kucinski, T; Ries, T; Zeumer, H, 2006)
"Two of the intracerebral hemorrhages occurred in the site where asymptomatic MBs were found at baseline."	1.32	Cerebral microbleeds as a risk factor for subsequent intracerebral hemorrhages among patients with acute ischemic stroke. ( Fan, YH; Lam, WW; Mok, VC; Wong, KS; Zhang, L, 2003)
"Stroke is a devastating complication in patients with prosthetic valves, but characterization of its late occurrence from a large cohort is lacking."	1.32	Late incidence and determinants of stroke after aortic and mitral valve replacement. ( Bédard, PJ; Goldstein, WG; Hendry, PJ; Masters, RG; Mesana, TG; Pipe, AL; Rubens, FD; Ruel, M, 2004)
"Hypertension was a more common risk factor in AS patients (69% AS patients vs."	1.32	Risk factors and in-hospital outcomes in stroke and myocardial infarction patients. ( Ivanusa, M; Ivanusa, Z, 2004)
"Aspirin treatment is recognized as an advantageous adjunct to thrombolytic agents in myocardial infarct patients."	1.29	Intravenous aspirin causes a paradoxical attenuation of cerebrovascular thrombolysis. ( Bednar, MM; Bennett, WF; Errett, CJ; Gross, CE; Thibodeaux, H; Thomas, GR, 1995)
"At autopsy, cerebral amyloid angiopathy (CAA) was found."	1.29	Fatal hemorrhage during anticoagulation of cardioembolic infarction: role of cerebral amyloid angiopathy. ( Bogousslavsky, J; Janzer, R; Melo, TP; Regli, F, 1993)
"Chronic subdural hematoma appears to be a suitable model for the evaluation of risk factors in the development of hemorrhage."	1.28	Aspirin as a risk factor for hemorrhage in patients with head injuries. ( Gratzl, O; Marbet, G; Radü, EW; Reymond, MA, 1992)
"Evidence of disseminated intravascular coagulation was found in 13 (62%) of the 21 cases at diagnosis."	1.28	Acute promyelocytic leukemia: impact of hemorrhagic complications on response to induction chemotherapy and survival. ( Hess, CE; Humphries, JE; Stewart, FM, 1990)
"A patient is reported who sustained a cerebral infarction from carotid artery disease and was treated with aspirin."	1.27	Aspirin, anticoagulants, and hemorrhagic conversion of ischemic infarction: hypothesis and implications. ( Fisher, M, 1986)
"Anticoagulant treatment after cerebral infarcts is still debated due to the imperfectly evaluated risk of hemorrhagic transformation."	1.27	[Late hemorrhagic transformation of cerebellar infarction under anticoagulant treatment]. ( Cambier, J; Charlier, P; Masson, C; Masson, M, 1985)

Research

Studies (279)

Authors

Clinical Trials (32)

Trial Overview

Trial Outcomes

Bleeding Event That Fulfils Serious Adverse Event Criteria and is Categorised as GUSTO Moderate/Severe

Timeframe	Studies, this research(%)	All Research%
pre-1990	24 (8.60)	18.7374
1990's	60 (21.51)	18.2507
2000's	88 (31.54)	29.6817
2010's	86 (30.82)	24.3611
2020's	21 (7.53)	2.80

Authors	Studies
Johnston, SC	2
Amarenco, P	1
Aunes, M	1
Denison, H	1
Evans, SR	1
Himmelmann, A	2
Jahreskog, M	1
James, S	1
Knutsson, M	1
Ladenvall, P	1
Molina, CA	2
Nylander, S	1
Röther, J	1
Wang, Y	5
Cheng, Y	3
Shao, T	1
Huang, L	1
Xu, H	1
Shao, P	1
Yang, D	1
Ge, W	1
Xu, Y	1
Zhang, M	2
Yang, J	1
Mo, S	1
Wang, K	1
Liu, Q	1
Wu, J	3
Yang, S	1
Guo, R	1
Yang, Y	1
Zhang, J	2
Liu, Y	1
Jiang, P	1
Cao, Y	1
Wang, S	2
Tang, M	1
Shin, HJ	1
Metcalf-Doetsch, W	1
Luo, Y	1
Lindholm, PF	2
Kwaan, H	1
Naidech, AM	6
Sharma, M	5
Smith, EE	5
Pearce, LA	5
Perera, KS	1
Kasner, SE	2
Yoon, BW	2
Ameriso, SF	1
Puig, J	1
Damgaard, D	1
Fiebach, JB	1
Muir, KW	2
Veltkamp, RC	1
Toni, DS	1
Shamalov, N	1
Gagliardi, RJ	1
Mikulik, R	3
Engelter, ST	1
Bereczki, D	2
O'Donnell, MJ	3
Saad, F	1
Shoamanesh, A	4
Berkowitz, SD	2
Mundl, H	2
Hart, RG	11
Duan, C	1
Xiong, Y	1
Gu, H	1
Yang, KX	1
Hao, M	1
Feng, X	1
Zhao, X	2
Meng, X	2
Clares de Andrade, JB	1
Mohr, JP	8
Lima, FO	1
de Carvalho, JJF	1
Maia Barros, LC	1
Pontes-Neto, OM	1
de Abreu, GQ	1
Silva, GS	1
Chen, HS	1
Cui, Y	1
Zhou, ZH	1
Zhang, H	1
Wang, LX	1
Wang, WZ	1
Shen, LY	1
Guo, LY	1
Wang, EQ	1
Wang, RX	1
Han, J	1
Dong, YL	1
Li, J	1
Lin, YZ	1
Yang, QC	1
Zhang, L	2
Li, JY	1
Wang, J	1
Xia, L	1
Ma, GB	1
Lu, J	1
Jiang, CH	1
Huang, SM	1
Wan, LS	1
Piao, XY	1
Li, Z	2
Li, YS	1
Yang, KH	1
Wang, DL	1
Nguyen, TN	1
Xu, LR	1
Zhao, Y	1
Huang, W	1
Cloud, GC	1
Williamson, JD	1
Thao, LTP	1
Tran, C	1
Eaton, CB	1
Wolfe, R	2
Nelson, MR	1
Reid, CM	1
Newman, AB	1
Lockery, J	1
Fitzgerald, SM	1
Murray, AM	1
Shah, RC	1
Woods, RL	2
Donnan, GA	4
McNeil, JJ	3
Cruz-Flores, S	1
Vidyanti, AN	1
Chan, L	1
Lin, CL	1
Muo, CH	1
Hsu, CY	1
Chen, YC	1
Wu, D	1
Hu, CJ	1
Murias, E	1
Vega, P	1
Lopez-Cancio, E	1
Peña, J	1
Morales, E	1
Benavente, L	1
González, M	1
Larrosa, D	1
Rico, M	1
Riesco, N	1
Cadenas, M	1
Jimenez, JM	1
Chaviano, J	1
Saiz, A	1
Calleja, S	1
Arias, F	1
Lee, TL	1
Liu, CH	1
Chang, YM	1
Lin, TY	1
Chien, CY	1
Chen, CH	1
Tsai, KJ	1
Lin, SH	1
Sung, PS	1
Wan, A	1
Butcher, K	1
Hodgson, M	1
Schultz, K	1
Bungard, TJ	1
Kim, BJ	3
Kwon, SU	3
Park, JH	2
Kim, YJ	2
Hong, KS	3
Wong, LKS	2
Yu, S	3
Hwang, YH	2
Lee, JS	3
Lee, J	2
Rha, JH	2
Heo, SH	2
Ahn, SH	2
Seo, WK	2
Park, JM	2
Lee, JH	2
Kwon, JH	2
Sohn, SI	2
Jung, JM	2
Navarro, JC	2
Kim, HY	1
Kim, EG	1
Kim, S	1
Cha, JK	1
Park, MS	1
Nam, HS	1
Kang, DW	2
Gomez-Paz, S	1
Salem, MM	1
Maragkos, GA	1
Ascanio, LC	1
Enriquez-Marulanda, A	1
Lee, M	1
Kicielinski, KP	1
Moore, JM	1
Thomas, AJ	1
Ogilvy, CS	1
Connolly, SJ	3
Martí-Fàbregas, J	3
Liu, YY	1
Uchiyama, S	3
Veltkamp, R	1
Ntaios, G	1
Field, TS	1
Santo, GC	1
Olavarria, V	1
Lutsep, H	1
Hald, SM	1
Möller, S	1
García Rodríguez, LA	3
Al-Shahi Salman, R	2
Christensen, H	3
Hellfritzsch, M	1
Pottegård, A	1
Hallas, J	1
Gaist, D	2
Aoki, J	1
Iguchi, Y	1
Urabe, T	2
Yamagami, H	1
Todo, K	1
Fujimoto, S	2
Idomari, K	1
Kaneko, N	1
Iwanaga, T	1
Terasaki, T	1
Tanaka, R	2
Yamamoto, N	1
Tsujino, A	1
Nomura, K	1
Abe, K	1
Uno, M	1
Okada, Y	3
Matsuoka, H	1
Yamagata, S	1
Yamamoto, Y	1
Yonehara, T	1
Inoue, T	2
Yagita, Y	1
Kimura, K	2
Albers, GW	2
Bernstein, R	1
Brachmann, J	1
Camm, AJ	2
Fromm, P	1
Goto, S	1
Granger, CB	2
Hohnloser, SH	2
Hylek, E	1
Krieger, D	1
Passman, R	1
Pines, JM	1
Kowey, P	1
Hoshino, H	1
Toyoda, K	2
Omae, K	1
Ishida, N	1
Sakai, N	1
Tanaka, K	1
Origasa, H	1
Naritomi, H	1
Houkin, K	1
Yamaguchi, K	1
Isobe, M	1
Minematsu, K	2
Matsumoto, M	1
Tominaga, T	1
Tomimoto, H	1
Terayama, Y	1
Yasuda, S	1
Yamaguchi, T	2
Bazan, C	1
Catanese, L	1
McClure, LA	1
Anderson, DC	1
Kase, CS	4
Benavente, OR	3
Aoun, M	1
Koubar, SH	1
Antoun, L	1
Tamim, H	1
Makki, M	1
Chelala, D	1
Cea Soriano, L	1
Soriano-Gabarró, M	1
Bromley, S	1
Cappellari, M	1
Turcato, G	1
Forlivesi, S	1
Zivelonghi, C	1
Bovi, P	1
Bonetti, B	1
Toni, D	2
Bruder, M	2
Won, SY	1
Wagner, M	1
Brawanski, N	1
Dinc, N	1
Kashefiolasl, S	1
Seifert, V	2
Konczalla, J	2
Kumar, S	1
de Lusignan, S	1
McGovern, A	1
Correa, A	1
Hriskova, M	1
Gatenby, P	1
Jones, S	1
Goldsmith, D	1
Würtz, M	1
Schmidt, M	1
Grove, EL	1
Horváth-Puhó, E	1
Henderson, VW	1
Christiansen, CF	1
Sørensen, HT	1
Raza, SA	1
Durm, LB	1
Mahmoud, GA	1
Rahman, H	1
Henriquez, L	1
Davis, B	1
Nahab, F	1
Izzy, S	1
Rubin, DB	1
Ahmed, FS	1
Akbik, F	1
Renault, S	1
Sylvester, KW	1
Vaitkevicius, H	1
Smallwood, JA	1
Givertz, MM	1
Feske, SK	2
Lee, EJ	1
Saber, H	1
Kherallah, RY	1
Hadied, MO	1
Kazemlou, S	1
Chamiraju, P	1
Narayanan, S	1
Majmundar, N	1
Sarris, C	1
Shastri, D	1
Doran, J	1
Gandhi, C	1
Assina, R	1
Chan, S	1
Brophy, M	1
Nishimura, N	1
Schaffer, CB	1
Ge, L	2
Ouyang, X	1
Ban, C	1
Yu, H	1
Wu, Q	2
Wu, H	2
Liang, J	1
Bouasquevisque, DS	1
Yamashiro, K	1
Okuma, Y	1
Ueno, Y	1
Tanaka, Y	1
Hattori, N	1
Elmer, J	1
Hou, P	1
Wilcox, SR	1
Chang, Y	1
Schreiber, H	1
Okechukwu, I	1
Pontes-Neto, O	1
Bajwa, E	1
Hess, DR	1
Avery, L	1
Duran-Mendicuti, MA	1
Camargo, CA	1
Greenberg, SM	2
Rosand, J	4
Pallin, DJ	1
Goldstein, JN	1
Beynon, C	1
Sakowitz, OW	1
Unterberg, AW	1
Homma, S	5
Thompson, JL	6
Sanford, AR	3
Mann, DL	5
Sacco, RL	6
Levin, B	5
Pullicino, PM	5
Freudenberger, RS	5
Teerlink, JR	5
Graham, S	5
Massie, BM	2
Labovitz, AJ	5
Di Tullio, MR	5
Gabriel, AP	2
Lip, GY	8
Estol, CJ	4
Lok, DJ	5
Ponikowski, P	5
Anker, SD	5
Qian, M	3
Haddad, H	1
Diek, M	1
Cordonnier, C	1
Leys, D	3
Sutcliffe, P	1
Connock, M	1
Gurung, T	1
Freeman, K	1
Johnson, S	1
Ngianga-Bakwin, K	1
Grove, A	1
Gurung, B	1
Morrow, S	1
Stranges, S	1
Clarke, A	1
Zhao, R	1
Feng, XY	1
Shen, XL	1
Su, JJ	1
Liu, JR	1
Gouya, G	1
Arrich, J	1
Wolzt, M	1
Huber, K	1
Verheugt, FW	3
Gurbel, PA	2
Pirker-Kees, A	1
Siller-Matula, JM	1
Takahashi, S	1
Mizuno, O	1
Sakaguchi, T	1
Yamada, T	1
Inuyama, L	1
Loidi Pascual, L	1
Valcayo Peñalba, A	1
Yerani Ruiz de Azúa Ciria, A	1
Yanguas Bayona, I	1
Eikelboom, J	1
Yusuf, S	4
Shestakovska, O	2
Connolly, S	2
Chalouhi, N	1
Zanaty, M	1
Jabbour, PM	1
Starke, RM	1
Tjoumakaris, SI	1
Rosenwasser, RH	1
Gonzalez, LF	1
Berkowitz, AL	1
Westover, MB	1
Bianchi, MT	1
Chou, SH	1
Paraskevas, KI	1
Veith, FJ	1
Selim, MH	1
Falcone, GJ	1
Dennis, MS	2
Zheng, H	1
Chen, C	1
Hu, Z	1
Yang, L	1
Shi, L	1
Pu, J	1
Xu, L	1
Malaguit, J	1
Chen, S	1
Martin-Yuste, V	1
Alvarez-Contreras, L	1
Sabaté, M	1
Kelbaek, H	1
Saunamäki, K	1
Jørgensen, E	1
Kocka, V	1
Ye, S	1
Buchsbaum, R	3
Lee, JY	1
Blann, AD	1
Skjøth, F	1
Rasmussen, LH	1
Larsen, TB	1
Engel-Haber, E	1
Horev, A	1
Chablani, P	1
Bornstein, NM	1
Jadhav, A	1
Jovin, TG	1
Reddy, V	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Randomised, Double-Blind, Placebo-Controlled, International, Multicentre, Phase III Study to Investigate the Efficacy and Safety of Ticagrelor and ASA Compared With ASA in the Prevention of Stroke and Death in Patients With Acute Ischaemic Stroke or Tra[NCT03354429]	Phase 3	11,016 participants (Actual)	Interventional	2018-01-22	Completed
Multicenter, Randomized, Double-blind, Double-dummy, Active-comparator, Event-driven, Superiority Phase III Study of Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With a Recent Embolic Stroke of Undetermined Source (ESUS),[NCT02313909]	Phase 3	7,213 participants (Actual)	Interventional	2014-12-23	Terminated (stopped due to Study halted early due to no efficacy improvement over aspirin at an interim analysis and very little chance of showing overall benefit if study were completed)
A Multicenter, Double Blind, Factorial Design, Phase IV Trial to Compare the Efficacy and Safety of Cilostazol Long-term Treatment With Aspirin in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage for the Prevention of Cerebral Hemorrhage and[NCT01013532]	Phase 4	1,600 participants (Anticipated)	Interventional	2009-06-30	Active, not recruiting
Low-dose Aspirin Therapy in Patients With Non-Cardioembolic Ischemic Stroke and Microbleeds[NCT04504864]	Phase 4	400 participants (Anticipated)	Interventional	2020-10-01	Recruiting
Antithrombotic Drug Use in Patients With Ischemic Stroke and Microbleeds[NCT05032053]		3,000 participants (Anticipated)	Observational [Patient Registry]	2022-03-01	Recruiting
Cilostazol Stroke Prevention Study for Antiplatelet Combination[NCT01995370]	Phase 4	1,884 participants (Actual)	Interventional	2013-12-13	Completed
A Pharmacoepidemiological Study on the Risk of Bleeding in New Users of Low-dose Aspirin (ASA) in The Health Improvement Network (THIN), UK[NCT02550717]		398,158 participants (Actual)	Observational	2015-09-01	Completed
Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial[NCT00041938]	Phase 3	2,305 participants (Actual)	Interventional	2002-10-31	Completed
Improving Outcome in Subarachnoid Hemorrhage wIth Nadroparine[NCT04507178]	Phase 2	100 participants (Anticipated)	Interventional	2022-02-02	Recruiting
Randomized,Double-blind Trial Comparing the Effects of a 3-month Clopidogrel Regimen,Combined With ASA During the First 21days,Versus ASA Alone for the Acute Treatment of TIA or Minor Stroke[NCT00979589]	Phase 3	5,100 participants (Actual)	Interventional	2009-12-31	Completed
China Research for Severe Spontaneous Intracerebral Hemorrhage（CRISIH）[NCT05975398]		450 participants (Anticipated)	Observational [Patient Registry]	2022-07-01	Recruiting
Effect and Safety of Surgical Intervention for Severe Spontaneous Intracerebral Hemorrhage Patients on Long-term Oral Antiplatelet Treatment[NCT05766865]		450 participants (Actual)	Observational	2019-07-10	Completed
Antithrombotic Therapy After Left Atrial Appendage Occlusion: Double Antiplatelet Therapy vs Apixaban[NCT05632445]	Phase 4	160 participants (Actual)	Interventional	2019-05-01	Completed
A Randomized Controlled Trial of Influenza Vaccine to Prevent Adverse Vascular Events: A Pilot Study[NCT01945268]	Phase 4	107 participants (Actual)	Interventional	2015-04-30	Completed
Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial[NCT04696120]	Phase 2	200 participants (Anticipated)	Interventional	2021-03-02	Not yet recruiting
A Randomized Controlled Trial of Influenza Vaccine to Prevent Adverse Vascular Events[NCT02762851]	Phase 4	5,000 participants (Anticipated)	Interventional	2016-06-30	Recruiting
Secondary Prevention of Small Subcortical Strokes (SPS3) Trial[NCT00059306]	Phase 3	3,020 participants (Actual)	Interventional	2003-02-28	Completed
Cilostazol Stroke Prevention Study-a Randomized, Double Blind, Double Dummy, Parallel Comparative, Multicenter Clinical Trial[NCT00202020]	Phase 3	720 participants	Interventional	2004-05-31	Completed
Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment: A Randomized Double-blind Trial[NCT00496769]	Phase 3	6,421 participants (Actual)	Interventional	2007-08-31	Completed
Effects of Task-oriented Progressive Resistance Strength Training and Balance Exercises in Functional Performance on Lower Limb in Individuals With Stroke[NCT04820660]		18 participants (Actual)	Interventional	2019-03-01	Completed
Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial[NCT00991029]	Phase 3	4,881 participants (Actual)	Interventional	2010-05-28	Terminated (stopped due to The trial was halted by the DSMB.)
Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence (FASTER)[NCT00109382]	Phase 2/Phase 3	500 participants (Anticipated)	Interventional	2003-05-31	Completed
Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke (ATAMIS): a Parallel Randomized, Open-label, Multicenter, Prospective Study[NCT02869009]	Phase 3	3,000 participants (Actual)	Interventional	2016-11-30	Completed
A REAl-life Study on Short-term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack[NCT05476081]		1,067 participants (Anticipated)	Observational [Patient Registry]	2021-02-03	Recruiting
Phase II, Randomized, Crossover, Single Blind, Safety Trial of DABIGATRAN Versus ASA for Preventing Ischaemic Brain Lesions in Patients Affected by CADASIL[NCT01361763]	Phase 2	50 participants (Anticipated)	Interventional	2011-06-30	Recruiting
Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A Randomized, Double-Blind, Aspirin-Controlled Trial[NCT00129805]	Phase 3	1,510 participants (Actual)	Interventional	2001-01-31	Completed
[NCT00000500]	Phase 3	0 participants	Interventional	1981-09-30	Completed
MRI Evaluation of Nidus Occlusion After Gamma Knife Radiosurgery of Cerebral Arteriovenous Malformations - A Prospective Preliminary Study[NCT03995823]		50 participants (Anticipated)	Observational	2019-07-01	Recruiting
Acute Ischaemic STROKE: From LABoratory to(2) the Patient's BED. Retrospective Study of Blood Biomarkers and Neuroimaging as Predictors of Cerebral Edema, Extension of Ischemic Injury and Functional Outcome[NCT05725694]		200 participants (Anticipated)	Observational	2015-10-01	Enrolling by invitation
WilL LOWer Dose Aspirin be More Effective Following ACS? (WILLOW-ACS)[NCT02741817]	Phase 4	20 participants (Actual)	Interventional	2016-06-26	Completed
Prevalence of Aspirin Resistance in Ischemic Stroke Patients at Assiut University Hospital[NCT05151263]		133 participants (Anticipated)	Observational	2023-11-01	Not yet recruiting
The Impact of Aspirin Dose Modification on the Innate Immune Response - Will Lower Dose Aspirin Therapy Reduce the Response to Endotoxin[NCT03869268]	Phase 4	72 participants (Actual)	Interventional	2019-04-24	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Participants with bleeding event that fulfils serious adverse event criteria and is categorised as GUSTO Moderate/Severe. GUSTO is a bleeding scale (GUSTO = Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries). GUSTO Severe bleeding is defined as any of the following: (1) fatal bleeding, (2) intracranial bleeding, or (3) bleeding that caused haemodynamic compromise requiring intervention. GUSTO Moderate bleeding is a bleeding requiring transfusion of whole blood or packed red blood cells without haemodynamic compromise (NCT03354429)
Timeframe: From randomisation (day 1) to visit 3 (day 30-34)

Bleeding Event That Fulfils Serious Adverse Event Criteria and is Categorised as GUSTO Severe

Intervention	Participants (Count of Participants)
TICAGRELOR	36
PLACEBO	11

Participants with bleeding event that fulfils serious adverse event criteria and is categorised as GUSTO Severe. GUSTO is a bleeding scale (GUSTO = Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries). GUSTO Severe bleeding is defined as any of the following: (1) fatal bleeding, (2) intracranial bleeding, or (3) bleeding that caused haemodynamic compromise requiring intervention (NCT03354429)
Timeframe: From randomisation (day 1) to visit 3 (day 30-34)

Composite of Subsequent Stroke or Death

Intervention	Participants (Count of Participants)
TICAGRELOR	28
PLACEBO	7

Participants with subsequent stroke or death (NCT03354429)
Timeframe: From randomisation (day 1) to visit 3 (day 30-34)

ICH or Fatal Bleeding Event

Intervention	Participants (Count of Participants)
TICAGRELOR	303
PLACEBO	362

Participants with ICH or fatal bleeding event (NCT03354429)
Timeframe: From randomisation (day 1) to visit 3 (day 30-34)

Ischaemic Stroke

Intervention	Participants (Count of Participants)
TICAGRELOR	22
PLACEBO	6

Number of participants with ischaemic stroke (NCT03354429)
Timeframe: From randomisation (day 1) to visit 3 (day 30-34)

Number of Participants With Modified Rankin Scale (mRS) Score >1 at Visit 3

Intervention	Participants (Count of Participants)
TICAGRELOR	276
PLACEBO	345

The modified Rankin Scale (mRS) is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death.0 - No symptoms,1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead. (NCT03354429)
Timeframe: Visit 3 (day 30-34)

Premature Permanent Discontinuation of IP Due to Bleeding

Intervention	Participants (Count of Participants)
TICAGRELOR	1282
PLACEBO	1284

Participants with premature permanent discontinuation of IP due to bleeding (NCT03354429)
Timeframe: From randomisation (day 1) to visit 3 (day 30-34)

Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated)

Intervention	Participants (Count of Participants)
TICAGRELOR	152
PLACEBO	32

Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (>=) 2 grams per decilitre (g/dL) (20 grams per liter [g/L]; 1.24 millimoles per liter [mmol/L]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred. (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Incidence Rate of All-Cause Mortality

Intervention	event/100 participant-years (Number)
Rivaroxaban 15 mg OD	1.82
Acetylsalicylic Acid 100 mg OD	0.67

All-cause mortality includes all deaths of participants due to any cause. (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction

Intervention	event/100 participant-years (Number)
Rivaroxaban 15 mg OD	1.88
Acetylsalicylic Acid 100 mg OD	1.50

Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. Cardiovascular death includes death due to hemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging. (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Incidence Rate of Clinically Relevant Non-Major Bleeding Events

Intervention	event/100 participant-years (Number)
Rivaroxaban 15 mg OD	6.20
Acetylsalicylic Acid 100 mg OD	5.85

Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Incidence Rate of Intracranial Hemorrhage

Intervention	event/100 participant-years (Number)
Rivaroxaban 15 mg OD	3.52
Acetylsalicylic Acid 100 mg OD	2.32

Intracranial hemorrhage included all bleeding events that occurred in intracerebral, sub arachnoidal as well as subdural or epidural sites. The below table displays results for all randomized participants and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Incidence Rate of Life-Threatening Bleeding Events

Intervention	event/100 participant-years (Number)
Rivaroxaban 15 mg OD	0.70
Acetylsalicylic Acid 100 mg OD	0.35

Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Incidence Rate of the Composite Efficacy Outcome (Adjudicated)

Intervention	event/100 participant-years (Number)
Rivaroxaban 15 mg OD	1.02
Acetylsalicylic Acid 100 mg OD	0.43

Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred. (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke, Cardiovascular (CV) Death, Myocardial Infarction

Intervention	event/100 participant-years (Number)
Rivaroxaban 15 mg OD	5.14
Acetylsalicylic Acid 100 mg OD	4.78

"Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to moderate disability (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from moderately severe disability (unable to walk or to attend to own bodily needs without assistance)through to death. CV death includes death due to hemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging." (NCT02313909)
Timeframe: From randomization until the efficacy cut-off date (median 326 days)

Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death

Intervention	event/100 participant-years (Number)
	Stroke	Ischemic stroke	Disabling stroke	CV death(includes death due to hemorrhage)	Myocardial infarction
Acetylsalicylic Acid 100 mg OD	4.71	4.56	0.84	0.66	0.67
Rivaroxaban 15 mg OD	5.11	4.71	1.20	0.99	0.49

The time, in years, from randomization to the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years

Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome

Intervention	events per 100 patient-years (Number)
Aspirin	7.93
Warfarin	7.47

Time, in years, from randomization to death component of secondary composite outcome. This measure counts only deaths that were not preceded by heart failure hospitalization, myocardial infarction, ischemic stroke, or intracerebral hemorrhage. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of death component of secondary composite outcome, up to 6 years

Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.

Intervention	events per 100 patient years (Number)
Aspirin	4.41
Warfarin	4.43

Time, in years, from date of randomization to date of heart failure hospitalization, up to 6 years. Includes hospitalizations for heart failure during follow-up that were not preceded by myocardial infarction. Event rate per 100 patient years = 100*(number of subjects with heart failure hospitalization)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years

Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome

Intervention	events per 100 patient years (Number)
Aspirin	5.67
Warfarin	6.79

Time, in years, from date of randomization to date of intracerebral hemorrhage component of secondary composite outcome. Includes only intracerebral hemorrhages not preceded by myocardial infarction or heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years

Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome

Intervention	events per 100 patient years (Number)
Aspirin	0.06
Warfarin	0.11

Ischemic stroke component of secondary composite endpoint. Includes only ischemic strokes that were not preceded by a myocardial infarction or heart failure hospitalization. The number of ischemic strokes that are components of the secondary outcome does not therefore match the number of ischemic strokes that are components of the primary outcome. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years

Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome

Intervention	events per 100 patient years (Number)
Aspirin	1.14
Warfarin	0.57

Time, in years, from date of randomization to date of myocardial infarction, up to 6 years. Includes only myocardial infarctions that occurred during follow-up, before any heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with myocardial infarction)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years

Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.

Intervention	events per 100 patient years (Number)
Aspirin	0.87
Warfarin	0.80

"The time, in years, from date of randomization to the date of the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to 6 years.~Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25." (NCT00041938)
Timeframe: From randomization to the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years.

Event Rate Per 100 Patient-years for Death

Intervention	events per 100 patient-years (Number)
Aspirin	12.15
Warfarin	12.70

Time, in years, from date of randomization to date of death component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of death component of primary composite outcome, up to 6 years

Event Rate Per 100 Patient-years for Intracerebral Hemorrhage

Intervention	events per 100 patient-years (Number)
Aspirin	6.52
Warfarin	6.63

Time, in years, from date of randomization to date of intracerebral hemorrhage component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years

Event Rate Per 100 Patient-years for Ischemic Stroke

Intervention	rate per 100 patient years (Number)
Aspirin	0.05
Warfarin	0.12

Time, in years, from date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years

Rate Per 100 Patient Years of Major Hemorrhage

Intervention	rate per 100 patient years (Number)
Aspirin	1.36
Warfarin	0.72

Rate/100 patient-years of major hemorrhage. Includes all major hemorrhages in any patient. Major hemorrhage was defined as intracerebral, epidural, subdural, subarachnoid, spinal intramedullary, or retinal hemorrhage; any other bleeding causing a decline in the hemoglobin level of more than 2 g per deciliter in 48 hours; or bleeding requiring transfusion of 2 or more units of whole blood, hospitalization, or surgical intervention. Event rate per 100 patient years = 100*(number of major hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization until end of scheduled follow-up, up to 6 years

Rate Per 100 Patient-years of Minor Hemorrhage.

Intervention	events per 100 patient years (Number)
Aspirin	0.87
Warfarin	1.78

Rate per 100 patient years of minor hemorrhage. Includes all minor hemorrhages. Minor hemorrhage was defined as any non-major hemorrhage. Event rate per 100 patient years = 100*(number of minor hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25. (NCT00041938)
Timeframe: From date of randomization until the end of scheduled follow-up, up to 6 years

Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period

Intervention	events per 100 patient-years (Number)
Aspirin	7.34
Warfarin	11.6

Event rate=percent of participants with an event divided by the total participants in the arm. (NCT00496769)
Timeframe: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)

Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period

Intervention	Percentage of events per year (Number)
Apixaban, 2.5 or 5 mg Twice Daily	4.21
Acetylsalicylic Acid, 81-324 mg Once Daily	6.35

Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.) (NCT00496769)
Timeframe: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)

Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period

Intervention	Percentage of events (Number)
Apixaban, 2.5 or 5 mg Twice Daily	1.62
Acetylsalicylic Acid, 81-324 mg Once Daily	3.63

Event rate=percent of participants with an event divided by the total participants in the arm. (NCT00496769)
Timeframe: Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)

Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death

Intervention	Percentage of events per year (Number)
Apixaban, 2.5 or 5 mg Twice Daily	10.85
Acetylsalicylic Acid, 81-324 mg Once Daily	8.32

Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period

Intervention	Percentage of events per year (Number)
	All-cause death (n=111, 140)	Net clinical benefit (n=163, 220)	Vascular death (n=84, 96)
Acetylsalicylic Acid, 81-324 mg Once Daily	4.42	7.13	3.03
Apixaban, 2.5 or 5 mg Twice Daily	3.51	5.23	2.65

Event rate=percent of participants with an event divided by the total participants in the arm. (NCT00496769)
Timeframe: First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality

Intervention	Percentage of events per year (Number)
	Major bleeding	Major or CRNM bleeding	All bleeding
Acetylsalicylic Acid, 81-324 mg Once Daily	0.92	3.24	8.32
Apixaban, 2.5 or 5 mg Twice Daily	1.41	4.46	10.85

BL=baseline, LLN=lower limit of normal, ULN=upper limit of normal. Hemoglobin (g/dL), low: BL>2 or value ≤8; hematocrit(%), low: <0.75*BL; erythrocytes (*10^6 cells/μL), low: <0.75*BL; platelet count (*10^9 cells/L),low: <100*10^9 cells/L; leukocytes (*10^3 cells/μL), low if <0.8*BL and BLULN or <0.75*LLN when BL is missing or LLN ≤BL≤ ULN, high if >1.2*BL and BL>ULN or >ULN when BL and BL1.25*ULN when BL is missing or LLN≤BL≤ULN; neutrophils (absolute), low: <1.0*10^3 cells/μL; eosinophils (absolute), high: >0.750*10^3 cells/μL; basophils (absolute), high: >0.4*10^3 cells/μL; monocytes (absolute), high: 2*10^3 cells/μL; lymphocytes (absolute), low if <0.75*10^3 cells/μL, high if >7.50*10^3 cells/μL; ALP (U/L), high: 2*ULN; AST (U/L), high: 3*ULN; AST (U/L), high: 3*ULN; bilirubin, total (mg/dL), high: >2*ULN; bilirubin, direct (mg/dL), high: 1.5*ULN; BUN (mg/dL), high:>2*ULN; creatinine (mg/dL), high: >1.5*ULN. (NCT00496769)
Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)

Intervention	Participants (Number)
	Hemoglobin, low (n=1956, 1893)	Hemoglobin, high (n=1956, 1893)	Hematocrit, low (n=1728, 1687)	Hematocrit, high (n=1728, 1687)	Erythrocytes, low (n=1728, 1687)	Erythrocytes, high (n=1728, 1687)	Platelet count, low (n=2148, 2098)	Platelet count, high (n=2148, 2098)	Leukocytes, low (n=1738, 1698)	Leukocytes, high (n=1738, 1698)	Neutrophils (absolute), low (n=2170, 2138)	Neutrophils (absolute), high (n=2170, 2138)	Eosinophils (absolute), low (n=2170, 2138)	Eosinophils (absolute), high (n=2170, 2138)	Basophils (absolute), low (n=2170, 2138)	Basophils (absolute), high (n=2170, 2138)	Monocytes (absolute), low (n=2170, 2138)	Monocytes (absolute), high (n=2170, 2138)	Lymphocytes (absolute), low (n=2170, 2138)	Lymphocytes (absolute), high (n=2170, 2138)	Alkaline phosphatase (ALP), low (n=2781, 2758)	ALP, high (n=2781, 2758)	Aspartate phosphatase (AST), low (n=2779, 2753)	AST, high (n=2779, 2753)	Alanine aminotransferase (ALT), low (n=2779, 2753)	ALT, high (n=2779, 2753)	Bilirubin (total), low (n=2781, 2758)	Bilirubin (total), high (n=2781, 2758)	Bilirubin (direct), low (n=2773, 2750)	Bilirubin (direct), high (n=2773, 2750)	Blood urea nitrogen (BUN), low (n=2201, 2172)	BUN, high (n=2201, 2172)	Creatinine, low (n=2209, 2178)	Creatinine, high (n=2209, 2178)
Acetylsalicylic Acid, 81-324 mg Once Daily	120	0	9	0	12	0	10	0	14	18	1	0	0	68	0	0	0	2	62	5	0	27	0	33	0	31	0	43	0	248	0	50	0	71
Apixaban, 2.5 or 5 mg Twice Daily	131	0	13	0	12	0	7	0	12	14	2	0	0	48	0	0	0	0	52	4	0	34	0	28	0	23	0	30	0	241	0	42	0	67

LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Sodium, serum (mEq/L):low if <0.95*BL and BLULN or <0.95*LLN when BL missing or LLN ≤BL≤ULN, high if >1.05*BL and BL>ULN or >ULN and BL1.05*ULN when BL missing or LLN≤BL≤ULN; potassium(mEq/L):low if <0.90*BL and BLULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL and BL>ULN or>ULN and BL1.10*ULN when BL missing or LLN≤BL≤ULN; chloride(mEq/L):low if <0.90*BL and BLULN or <0.90*LLN if BL missing or LLN≤BL ≤ULN, high if >1.10*BL and BL>ULN or >ULN and BL1.10* ULN if BL missing or LLN≤BL≤ULN; calcium(mg/dL):low if <0.75*BL and BLULN or <0.80*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL and BL>ULN or >ULN if BL1.20*ULN if BL missing or LLN≤BL≤ULN ; bicarbonate(mEq/L):low if <0.75*BL when BLULN or <0.75*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL when BL>ULN or >ULN (NCT00496769)
Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)

Intervention	Participants (Number)
	Sodium (serum), low (n=1768, 1740)	Sodium (serum), high (n=1768, 1740)	Potassium (serum), low (n=1763, 1737)	Potassium (serum), high (n=1763, 1737)	Chloride (serum), low (n=1768, 1740)	Chloride (serum), high (n=1768, 1740)	Calcium (total), low (n=106, 109)	Calcium (total), high (n=106, 109)	Bicarbonate, low (n=1664, 1619)	Bicarbonate, high (n=1664, 1619)
Acetylsalicylic Acid, 81-324 mg Once Daily	6	2	8	28	3	1	0	0	0	0
Apixaban, 2.5 or 5 mg Twice Daily	2	1	6	20	0	0	0	0	0	0

ULN=upper limit of normal; LLN=lower limit of normal; BL=baseline. Creatine kinase (U/L), high:>5*ULN; protein, total(g/L):low if <0.90*BL when BLULN or <0.90*LLN when BL is missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN when BL1.10*ULN if BL missing or LLN≤BL≤ULN.Protein,total(g/L): low if <0.90*BL if BLULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN if BL1.10*ULN if BL or LLN≤BL≤ULN; glucose, serum fasting (mg/dL): low if <0.8*BL if BLULN or <0.8*LLN when BL missing or LLN≤BL≤ULN, high if >2*BL when BL>ULN or >ULN when BL1.5*ULN if BL missing or LLN≤BL≤ULN; uric acid (mg/dL), high: >2*BL and BL>ULN or>1.5*ULN when BL missing or BL≤ULN; glucose, urine, high; protein, urine, high; blood, urine, high; leukocyte esterase, urine, high; RBC count, urine (Hpf), high; WBC count, urine (Hpf), high: ≥2 if BL=missing,=0 or =0.5 or if ≥3 if BL=1, or if ≥4 and BL≥2. (NCT00496769)
Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome

Intervention	Participants (Number)
	Creatine kinase, low (n=2780, 2758)	Creatine kinase, high (n=2780, 2758)	Protein (total), low (n=103, 109)	Protein (total), high (n=103, 109)	Uric acid, low (n=386, 390)	Uric acid, high (n=386, 390)	Glucose (urine), low (n=2, 3)	Glucose (urine), high (n=2, 3)	Protein (urine), low (n=3, 5)	Protein (urine), high (n=3, 5)	Blood (urine), low (n=3, 5)	Blood (urine), high (n=3, 5)	Leukocyte esterase (urine), low (n=3,5)	Leukocyte esterase (urine), high (n=3,5)	Red blood cells (RBC) (urine), low (n=2,2)	RBC (urine), high (n=2,2)	White blood cells (urine), low (n=2,2)	WBC (urine), high (n=2,2)
Acetylsalicylic Acid, 81-324 mg Once Daily	0	25	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Apixaban, 2.5 or 5 mg Twice Daily	0	13	0	0	0	1	0	0	0	1	0	1	0	0	0	1	0	0

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. (NCT00496769)
Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Composite of Ischemic Stroke, Myocardial Infarction, Death From Ischemic Vascular Causes, or Major Hemorrhage

Intervention	Participants (Number)
	AEs	SAEs	Bleeding AEs	Discontinuations due to AE	Deaths
Acetylsalicylic Acid, 81-324 mg Once Daily	1925	804	259	362	115
Apixaban, 2.5 or 5 mg Twice Daily	1833	657	281	266	91

Secondary efficacy outcome: Number of participants with ischemic stroke, myocardial infarction, death from ischemic vascular causes, or major hemorrhage (NCT00991029)
Timeframe: Up to 90 days

Composite of Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes

Intervention	Participants (Count of Participants)
Clopidogrel	141
Placebo	167

Primary efficacy outcome: Number of Participants with Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes (NCT00991029)
Timeframe: Up to 90 days

Death From Any Cause

Intervention	Participants (Count of Participants)
Clopidogrel	121
Placebo	160

Other safety outcome: Number of Participants with Death from any cause (NCT00991029)
Timeframe: up to 90 days

Death From Ischemic Vascular Causes

Intervention	Participants (Count of Participants)
Clopidogrel	18
Placebo	12

Secondary efficacy outcome: Number of participants with Death from ischemic vascular causes (NCT00991029)
Timeframe: Up to 90 days

Hemorrhagic Stroke

Intervention	Participants (Count of Participants)
Clopidogrel	6
Placebo	4

Other safety outcome: Number of participants with Hemorrhagic stroke (NCT00991029)
Timeframe: up to 90 days

Ischemic or Hemorrhagic Stroke

Intervention	Participants (Count of Participants)
Clopidogrel	5
Placebo	3

Secondary efficacy outcome: Number of participants with Ischemic or hemorrhagic stroke (NCT00991029)
Timeframe: Up to 90 days

Ischemic Stroke

Intervention	Participants (Count of Participants)
Clopidogrel	116
Placebo	156

Secondary efficacy outcome:Number of participants with Ischemic stroke (NCT00991029)
Timeframe: Up to 90 days

Major Hemorrhage

Intervention	Participants (Count of Participants)
Clopidogrel	112
Placebo	155

Primary safety outcome: Number of Participants with major hemorrhage (NCT00991029)
Timeframe: Up to 90 days

Major Hemorrhage Other Than Intracranial Hemorrhage

Intervention	Participants (Count of Participants)
Clopidogrel	23
Placebo	10

Other safety outcome: Number of Participants with Major hemorrhage other than intracranial hemorrhage (NCT00991029)
Timeframe: up to 90 days

Minor Hemorrhage

Intervention	Participants (Count of Participants)
Clopidogrel	17
Placebo	7

Other safety outcome:Number of Participants with Minor hemorrhage (NCT00991029)
Timeframe: up to 90 days

Myocardial Infarction

Intervention	Participants (Count of Participants)
Clopidogrel	40
Placebo	13

Secondary efficacy outcome: Number of participants with Myocardial infarction (NCT00991029)
Timeframe: Up to 90 days

Other Symptomatic Intracranial Hemorrhage

Other safety outcome: Number of participants with other symptomatic intracranial hemorrhage (NCT00991029)
Timeframe: up to 90 days

Symptomatic Intracerebral Hemorrhage

Other safety outcome: Number of participants with Symptomatic intracerebral hemorrhage (NCT00991029)
Timeframe: up to 90 days

Article	Year
Reexamination of the Embolic Stroke of Undetermined Source Concept. Stroke, 2021, Volume: 52, Issue:8 Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Clinical Trials as Topic; Dual An	2021
Antiplatelet therapy and the risk of ischemic and hemorrhagic complications associated with Pipeline embolization of cerebral aneurysms: a systematic review and pooled analysis. Journal of neurointerventional surgery, 2019, Volume: 11, Issue:4 Topics: Adult; Aged; Aspirin; Blood Vessel Prosthesis; Brain Ischemia; Cerebral Hemorrhage; Embolization, Th	2019
Antiplatelet Therapy in Cerebral Small Vessel Disease. Current neurology and neuroscience reports, 2019, 07-27, Volume: 19, Issue:9 Topics: Aspirin; Cerebral Hemorrhage; Cerebral Small Vessel Diseases; Clopidogrel; Drug Therapy, Combination	2019
Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials. PloS one, 2013, Volume: 8, Issue:12 Topics: Aspirin; Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Humans; Male; Neoplasms; Platelet	2013
Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis. Stroke, 2014, Volume: 45, Issue:2 Topics: Adenosine; Aged; Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Clopidogrel; Cohort Studie	2014
Intracerebral hemorrhage after pipeline embolization: Management of antiplatelet agents and the case for point-of-care testing--case reports and review of literature. Clinical neurology and neurosurgery, 2014, Volume: 124 Topics: Aspirin; Cerebral Hemorrhage; Clinical Protocols; Clopidogrel; Drug Administration Schedule; Emboliz	2014
The efficacy and safety of cilostazol for the secondary prevention of ischemic stroke in acute and chronic phases in Asian population--an updated meta-analysis. BMC neurology, 2014, Dec-20, Volume: 14 Topics: Acute Disease; Asian People; Aspirin; Cerebral Hemorrhage; Cerebral Infarction; Chronic Disease; Cil	2014
Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation. An indirect comparison analysis. Thrombosis and haemostasis, 2015, Volume: 114, Issue:2 Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrhage; Clopidogrel; Drug	2015
Prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy: a systematic review and external validation study. Journal of thrombosis and haemostasis : JTH, 2016, Volume: 14, Issue:1 Topics: Algorithms; Anticoagulants; Aspirin; Brain Ischemia; Calibration; Cerebral Hemorrhage; Dipyridamole;	2016
Case Report and Review of Literature of Delayed Acute Subdural Hematoma. World neurosurgery, 2016, Volume: 96 Topics: Accidental Falls; Aged; Aspirin; Cerebral Hemorrhage; Decompressive Craniectomy; Female; Glasgow Com	2016
Optimal pediatric dosing of anti-platelet agents for pipeline stent embolization -a case report and review of the literature. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2017, Volume: 33, Issue:4 Topics: Adolescent; Aspirin; Bone Neoplasms; Cerebral Hemorrhage; Clopidogrel; Embolization, Therapeutic; Fe	2017
Aspirin in cardiology--benefits and risks. International journal of clinical practice, 2009, Volume: 63, Issue:3 Topics: Adult; Aged; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Female; Gastrointestinal Diseases; Humans	2009
P2X(1) receptor inhibition and soluble CD39 administration as novel approaches to widen the cardiovascular therapeutic window. Trends in cardiovascular medicine, 2009, Volume: 19, Issue:1 Topics: Adenosine Triphosphate; Antigens, CD; Apyrase; Aspirin; Biomedical Research; Cardiovascular Diseases	2009
[Pharmacotherapy of stroke]. Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology, 2009, Volume: 11, Issue:1 Topics: Acute Disease; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Hungary; N	2009
[Acetylsalicylic acid in the primary and secondary prevention of vascular disease]. Der Internist, 2010, Volume: 51, Issue:10 Topics: Aspirin; Cerebral Hemorrhage; Germany; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregati	2010
Aspirin in Alzheimer's disease: increased risk of intracerebral hemorrhage: cause for concern? Stroke, 2010, Volume: 41, Issue:11 Topics: Aged; Alzheimer Disease; Aspirin; Cerebral Hemorrhage; Humans; Incidence; Middle Aged; Platelet Aggr	2010
Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials. Stroke, 2012, Volume: 43, Issue:8 Topics: Adult; Aged; Aspirin; Cause of Death; Cerebral Hemorrhage; Clopidogrel; Data Interpretation, Statist	2012
How baseline severity affects efficacy and safety outcomes in acute ischemic stroke intervention trials. Annals of the New York Academy of Sciences, 2012, Volume: 1268 Topics: Acute Disease; Anticoagulants; Aspirin; Brain Damage, Chronic; Brain Ischemia; Cerebral Hemorrhage;	2012
Does inhibiting Sur1 complement rt-PA in cerebral ischemia? Annals of the New York Academy of Sciences, 2012, Volume: 1268 Topics: Animals; Antioxidants; Aspirin; ATP-Binding Cassette Transporters; Brain Ischemia; Cells, Cultured;	2012
Stroke management. Clinical evidence, 2002, Issue:7 Topics: Aspirin; Cerebral Hemorrhage; Cerebral Infarction; Combined Modality Therapy; Humans; Neuroprotectiv	2002
Stroke management. Clinical evidence, 2002, Issue:8 Topics: Aspirin; Cerebral Hemorrhage; Cerebral Infarction; Combined Modality Therapy; Humans; Neuroprotectiv	2002
Stroke management. Clinical evidence, 2003, Issue:9 Topics: Anticoagulants; Antihypertensive Agents; Aspirin; Cerebral Hemorrhage; Humans; Neuroprotective Agent	2003
Are anticoagulants better than antiplatelet agents for treatment of acute ischemic stroke? American family physician, 2003, Oct-01, Volume: 68, Issue:7 Topics: Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Evidence-Based Medicine; Humans; Plate	2003
What is the best imaging strategy for acute stroke? Health technology assessment (Winchester, England), 2004, Volume: 8, Issue:1 Topics: Aged; Aspirin; Brain; Cerebral Hemorrhage; Costs and Cost Analysis; Decision Support Techniques; Hum	2004
Risk of intracerebral hemorrhage in patients with arterial versus cardiac origin of cerebral ischemia on aspirin or placebo: analysis of individual patient data from 9 trials. Stroke, 2004, Volume: 35, Issue:3 Topics: Anti-Inflammatory Agents, Non-Steroidal; Arterial Occlusive Diseases; Aspirin; Atrial Fibrillation;	2004
Antithrombotic therapies for stroke prevention in atrial fibrillation. Minerva cardioangiologica, 2004, Volume: 52, Issue:2 Topics: Aged; Ambulatory Care Facilities; Anticoagulants; Aspirin; Atrial Fibrillation; Azetidines; Benzylam	2004
Management problems of spontaneous ICH. Hospital medicine (London, England : 1998), 2005, Volume: 66, Issue:4 Topics: Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Hospitalization; Humans; Magnetic Reso	2005
Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke, 2005, Volume: 36, Issue:7 Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Blood Pressur	2005
Risk of hemorrhagic stroke with aspirin use: an update. Stroke, 2005, Volume: 36, Issue:8 Topics: Adult; Aged; Aged, 80 and over; Angiography; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Brain	2005
Aspirin for the primary prevention of cardiovascular disease: a comprehensive review. Comprehensive therapy, 2005,Fall, Volume: 31, Issue:3 Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cardiovascular Diseases; Cerebral Hemorrhage; Dose	2005
New anticoagulants in ischemic heart disease. Presse medicale (Paris, France : 1983), 2005, Oct-22, Volume: 34, Issue:18 Topics: Anticoagulants; Aspirin; Azetidines; Benzylamines; Cerebral Hemorrhage; Coronary Thrombosis; Drug Th	2005
Best evidence topic report. Aspirin and the risk of intracranial complications following head injury. Emergency medicine journal : EMJ, 2005, Volume: 22, Issue:12 Topics: Aspirin; Cerebral Hemorrhage; Craniocerebral Trauma; Emergencies; Evidence-Based Medicine; Humans; P	2005
Advances in intracerebral hemorrhage management. Stroke, 2006, Volume: 37, Issue:2 Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cerebral Hemorrhage; Clinical Tria	2006
Pathophysiology and medical management of systemic hypertension in preeclampsia. Current hypertension reports, 2006, Volume: 8, Issue:6 Topics: Adrenergic beta-Antagonists; Aspirin; Calcium; Calcium Channel Blockers; Cerebral Hemorrhage; Female	2006
Clinical practice. Acute ischemic stroke. The New England journal of medicine, 2007, Aug-09, Volume: 357, Issue:6 Topics: Acute Disease; Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Contraindications; Diag	2007
Haemorrhagic stroke during anti-platelet therapy. European journal of anaesthesiology. Supplement, 2008, Volume: 42 Topics: Acute Coronary Syndrome; Aspirin; Cerebral Hemorrhage; Clinical Trials as Topic; Humans; Intracrania	2008
Cardiogenic cerebral embolism. Comprehensive therapy, 1984, Volume: 10, Issue:9 Topics: Anticoagulants; Aspirin; Cardiac Surgical Procedures; Cerebral Hemorrhage; Cerebral Infarction; Dipy	1984
Perinatal intracranial hemorrhage due to maternal salicylate ingestion. Clinical pediatrics, 1995, Volume: 34, Issue:3 Topics: Aspirin; Cerebral Hemorrhage; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; P	1995
Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis. The Online journal of current clinical trials, 1995, Mar-14, Volume: Doc No 174 Topics: Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Gastroint	1995
Aspirin and other nonsteroidal anti-inflammatory agents in the prevention of colorectal cancer. Important advances in oncology, 1996 Topics: Adenocarcinoma; Adenoma; Adenomatous Polyposis Coli; Adult; Animals; Anti-Inflammatory Agents, Non-S	1996
[Antithrombotic therapy of atrial fibrillation]. Archives des maladies du coeur et des vaisseaux, 1996, Volume: 89, Issue:11 Suppl Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Diso	1996
[Secondary prevention following cerebral ischemia: is monotherapy with acetylsalicylic acid still first choice?]. Nederlands tijdschrift voor geneeskunde, 1998, Feb-07, Volume: 142, Issue:6 Topics: Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Cerebrovascular Disorders; Clopidogrel	1998
Use and safety of aspirin in the chemoprevention of colorectal cancer. Journal of the Association for Academic Minority Physicians : the official publication of the Association for Academic Minority Physicians, 1998, Volume: 9, Issue:2 Topics: Aspirin; Cerebral Hemorrhage; Colorectal Neoplasms; Cyclooxygenase Inhibitors; Humans; Incidence; Pe	1998
Antithrombotic therapy in atrial fibrillation. Chest, 1998, Volume: 114, Issue:5 Suppl Topics: Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebrovascular Disorders; Electric Countershock;	1998
Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA, 1998, Dec-09, Volume: 280, Issue:22 Topics: Aspirin; Brain Ischemia; Cerebral Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation In	1998
Aspirin: real benefits, but real risks, too. Harvard heart letter : from Harvard Medical School, 1999, Volume: 9, Issue:9 Topics: Aspirin; Cardiovascular Diseases; Cerebral Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk	1999
[Neurological complications with analgesics]. Ryoikibetsu shokogun shirizu, 1999, Issue:27 Pt 2 Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cerebral Hemorrhage; Headache; Humans;	1999
Aspirin and heparin in acute ischaemic stroke in older patients. Drugs & aging, 1999, Volume: 15, Issue:1 Topics: Acute Disease; Aged; Anticoagulants; Aspirin; Brain Ischemia; Cerebral Hemorrhage; Cerebrovascular D	1999
Antithrombotic management of atrial fibrillation for stroke prevention in older people. Clinics in geriatric medicine, 1999, Volume: 15, Issue:4 Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Contraindications; Fibrinol	1999
Thrombolysis and percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction. Zeitschrift fur Kardiologie, 2000, Volume: 89 Suppl 4 Topics: Angioplasty, Balloon, Coronary; Antithrombins; Aspirin; Cerebral Hemorrhage; Clinical Trials, Phase	2000
Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke, 2000, Volume: 31, Issue:6 Topics: Acute Disease; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Cerebral Hemorrha	2000
[Fibrinolysis in myocardial infarction with EKG elevation. Optimization of myocardial reperfusion by treatment with antithrombotic agents]. Archives des maladies du coeur et des vaisseaux, 2001, Volume: 94, Issue:11 Suppl Topics: Aspirin; Cerebral Hemorrhage; Drug Costs; Electrocardiography; Fibrinolytic Agents; Hirudin Therapy;	2001
[Heparin or aspirin in the treatment of acute cerebral infarction?]. La Revue du praticien, 2001, Dec-01, Volume: 51, Issue:19 Topics: Aspirin; Cerebral Hemorrhage; Cerebral Infarction; Fibrinolytic Agents; Heparin; Humans; Patient Sel	2001
Haemorrhagic aspects of thrombolytic therapy. European heart journal, 1990, Volume: 11 Suppl F Topics: Anistreplase; Aspirin; Cerebral Hemorrhage; Heparin; Humans; Incidence; Myocardial Infarction; Strep	1990
Aspirin in stroke prevention. An overview. Stroke, 1990, Volume: 21, Issue:12 Suppl Topics: Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Female; Humans; Male	1990
[Antithrombotic drugs]. Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics, 1989, Volume: 26, Issue:2 Topics: Adult; Aged; Aged, 80 and over; Aging; Aspirin; Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Mi	1989
The potential danger of aspirin to patients with intracranial bleeding. Journal of medicine, 1973, Volume: 4, Issue:6 Topics: Aspirin; Blood Platelets; Cerebral Hemorrhage; Hemostasis; Humans; Platelet Adhesiveness	1973

aspirin and Cerebral Hemorrhage

Research Excerpts

Research

Studies (279)

Authors

Clinical Trials (32)

Trial Overview

Trial Outcomes

Bleeding Event That Fulfils Serious Adverse Event Criteria and is Categorised as GUSTO Moderate/Severe

Bleeding Event That Fulfils Serious Adverse Event Criteria and is Categorised as GUSTO Severe

Composite of Subsequent Stroke or Death

ICH or Fatal Bleeding Event

Ischaemic Stroke

Number of Participants With Modified Rankin Scale (mRS) Score >1 at Visit 3

Premature Permanent Discontinuation of IP Due to Bleeding

Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated)

Incidence Rate of All-Cause Mortality

Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction

Incidence Rate of Clinically Relevant Non-Major Bleeding Events

Incidence Rate of Intracranial Hemorrhage

Incidence Rate of Life-Threatening Bleeding Events

Incidence Rate of the Composite Efficacy Outcome (Adjudicated)

Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke, Cardiovascular (CV) Death, Myocardial Infarction

Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death

Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome

Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.

Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome

Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome

Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome

Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.

Event Rate Per 100 Patient-years for Death

Event Rate Per 100 Patient-years for Intracerebral Hemorrhage

Event Rate Per 100 Patient-years for Ischemic Stroke

Rate Per 100 Patient Years of Major Hemorrhage

Rate Per 100 Patient-years of Minor Hemorrhage.

Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period

Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period

Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period

Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death

Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)

Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome

Composite of Ischemic Stroke, Myocardial Infarction, Death From Ischemic Vascular Causes, or Major Hemorrhage

Composite of Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes

Death From Any Cause

Death From Ischemic Vascular Causes

Hemorrhagic Stroke

Ischemic or Hemorrhagic Stroke

Ischemic Stroke

Major Hemorrhage

Major Hemorrhage Other Than Intracranial Hemorrhage

Minor Hemorrhage

Myocardial Infarction

Other Symptomatic Intracranial Hemorrhage

Symptomatic Intracerebral Hemorrhage

Reviews

Trials

Other Studies