Risk for major bleeding in patients receiving ticagrelor compared with aspirin after transient ischemic attack or acute ischemic stroke in the SOCRATES study (acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes)

J.D. Easton, M. Aunes, G.W. Albers, P. Amarenco, S. Bokelund-Singh, H. Denison, S.R. Evans, P. Held, M. Jahreskog, J. Jonasson, K. Minematsu, C.A. Molina, Y. Wang, K.S.L. Wong, S.C. Johnston, Simona Marcheselli

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. © 2017 American Heart Association, Inc.
Original languageEnglish
Pages (from-to)907-916
Number of pages10
JournalCirculation
Volume136
Issue number10
DOIs
Publication statusPublished - 2017

Fingerprint

Transient Ischemic Attack
Aspirin
Stroke
Hemorrhage
Intracranial Hemorrhages
Safety
Ticagrelor
Therapeutics
Myocardial Infarction
Brain Infarction
Cerebral Infarction
Coronary Vessels
Blood Platelets
Confidence Intervals

Keywords

  • Aspirin
  • Hemorrhage
  • Ischemic attack
  • Platelet aggregation inhibitors
  • Stroke
  • Transient
  • acetylsalicylic acid
  • ticagrelor
  • adenosine
  • purinergic P2Y receptor antagonist
  • aged
  • aneurysm clipping
  • angioplasty
  • anticoagulant therapy
  • aortic aneurysm
  • Article
  • brain artery aneurysm
  • brain hemorrhage
  • carotid artery stenting
  • clinical trial
  • decompressive craniectomy
  • drug safety
  • female
  • gastrointestinal hemorrhage
  • human
  • internal carotid artery
  • loading drug dose
  • major clinical study
  • male
  • monotherapy
  • patient safety
  • percutaneous coronary intervention
  • priority journal
  • risk assessment
  • thorax surgery
  • thrombectomy
  • transient ischemic attack
  • treatment outcome
  • analogs and derivatives
  • bleeding
  • chemically induced
  • complication
  • Ischemic Attack, Transient
  • risk
  • Adenosine
  • Aged
  • Female
  • Humans
  • Male
  • Purinergic P2Y Receptor Antagonists
  • Risk
  • Treatment Outcome

Cite this

Risk for major bleeding in patients receiving ticagrelor compared with aspirin after transient ischemic attack or acute ischemic stroke in the SOCRATES study (acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes). / Easton, J.D.; Aunes, M.; Albers, G.W.; Amarenco, P.; Bokelund-Singh, S.; Denison, H.; Evans, S.R.; Held, P.; Jahreskog, M.; Jonasson, J.; Minematsu, K.; Molina, C.A.; Wang, Y.; Wong, K.S.L.; Johnston, S.C.; Marcheselli, Simona.

In: Circulation, Vol. 136, No. 10, 2017, p. 907-916.

Research output: Contribution to journalArticle

Easton, JD, Aunes, M, Albers, GW, Amarenco, P, Bokelund-Singh, S, Denison, H, Evans, SR, Held, P, Jahreskog, M, Jonasson, J, Minematsu, K, Molina, CA, Wang, Y, Wong, KSL, Johnston, SC & Marcheselli, S 2017, 'Risk for major bleeding in patients receiving ticagrelor compared with aspirin after transient ischemic attack or acute ischemic stroke in the SOCRATES study (acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes)', Circulation, vol. 136, no. 10, pp. 907-916. https://doi.org/10.1161/CIRCULATIONAHA.117.028566
Easton, J.D. ; Aunes, M. ; Albers, G.W. ; Amarenco, P. ; Bokelund-Singh, S. ; Denison, H. ; Evans, S.R. ; Held, P. ; Jahreskog, M. ; Jonasson, J. ; Minematsu, K. ; Molina, C.A. ; Wang, Y. ; Wong, K.S.L. ; Johnston, S.C. ; Marcheselli, Simona. / Risk for major bleeding in patients receiving ticagrelor compared with aspirin after transient ischemic attack or acute ischemic stroke in the SOCRATES study (acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes). In: Circulation. 2017 ; Vol. 136, No. 10. pp. 907-916.
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title = "Risk for major bleeding in patients receiving ticagrelor compared with aspirin after transient ischemic attack or acute ischemic stroke in the SOCRATES study (acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes)",
abstract = "BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5{\%}) on ticagrelor and 38 patients (0.6{\%}) on aspirin (hazard ratio, 0.83; 95{\%} confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2{\%}) on ticagrelor and 18 patients (0.3{\%}) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. {\circledC} 2017 American Heart Association, Inc.",
keywords = "Aspirin, Hemorrhage, Ischemic attack, Platelet aggregation inhibitors, Stroke, Transient, acetylsalicylic acid, ticagrelor, adenosine, purinergic P2Y receptor antagonist, aged, aneurysm clipping, angioplasty, anticoagulant therapy, aortic aneurysm, Article, brain artery aneurysm, brain hemorrhage, carotid artery stenting, clinical trial, decompressive craniectomy, drug safety, female, gastrointestinal hemorrhage, human, internal carotid artery, loading drug dose, major clinical study, male, monotherapy, patient safety, percutaneous coronary intervention, priority journal, risk assessment, thorax surgery, thrombectomy, transient ischemic attack, treatment outcome, analogs and derivatives, bleeding, chemically induced, complication, Ischemic Attack, Transient, risk, Adenosine, Aged, Female, Humans, Male, Purinergic P2Y Receptor Antagonists, Risk, Treatment Outcome",
author = "J.D. Easton and M. Aunes and G.W. Albers and P. Amarenco and S. Bokelund-Singh and H. Denison and S.R. Evans and P. Held and M. Jahreskog and J. Jonasson and K. Minematsu and C.A. Molina and Y. Wang and K.S.L. Wong and S.C. Johnston and Simona Marcheselli",
note = "Cited By :1 Export Date: 2 March 2018 CODEN: CIRCA Correspondence Address: Johnston, S.C.; Dell Medical School, University of Texas at Austin, 1501 Red River St Stop ZO100, United States; email: clay.johnston@austin.utexas.edu Chemicals/CAS: acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1; ticagrelor, 274693-27-5; adenosine, 58-61-7; Adenosine; Aspirin; Purinergic P2Y Receptor Antagonists; Ticagrelor References: Husted, S., Emanuelsson, H., Heptinstall, S., Sandset, P.M., Wickens, M., Peters, G., Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: A double-blind comparison to clopidogrel with aspirin (2006) Eur Heart J, 27, pp. 1038-1047; Storey, R.F., Husted, S., Harrington, R.A., Heptinstall, S., Wilcox, R.G., Peters, G., Wickens, M., Cannon, C.P., Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes (2007) J Am Coll Cardiol, 50, p. 1852; Armstrong, D., Summers, C., Ewart, L., Nylander, S., Sidaway, J.E., Van Giezen, J.J., Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant inhibition of equilibrative nucleoside transporter 1 (2014) J Cardiovasc Pharmacol Ther, 19, pp. 209-219; James, S., Akerblom, A., Cannon, C.P., Emanuelsson, H., Husted, S., Katus, H., Skene, A., Wallentin, L., Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial (2009) Am Heart J, 157, p. 599; Wallentin, L., Becker, R.C., Budaj, A., Cannon, C.P., Emanuelsson, H., Held, C., Horrow, J., Thors{\'e}n, M., Ticagrelor versus clopidogrel in patients with acute coronary syndromes (2009) N Engl J Med, 361, pp. 1045-1057; Bonaca, M.P., Goto, S., Bhatt, D.L., Steg, P.G., Storey, R.F., Cohen, M., Goodrich, E., Ruda, M., (2016) Circulation, 134, pp. 861-871. , Morrow DA, Braunwald E, Sabatine MS. Prevention of stroke with ticagrelor in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54; Johnston, S.C., Amarenco, P., Albers, G.W., Denison, H., Easton, J.D., Evans, S.R., Held, P., Wong, K.S., And Investigators. Ticagrelor versus aspirin in acute stroke or transient ischemic attack (2016) N Engl J Med, 375, pp. 35-43; Johnston, S.C., Amarenco, P., Albers, G.W., Denison, H., Easton, J.D., Held, P., Jonasson, J., Wong, L.K., Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: Rationale and design (2015) Int J Stroke, 10, pp. 1304-1308; Serebruany, V.L., Steinhubl, S.R., Berger, P.B., Malinin, A.I., Baggish, J.S., Bhatt, D.L., Topol, E.J., Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials (2005) Am J Cardiol, 95, pp. 1218-1222; Diener, H.C., Bogousslavsky, J., Brass, L.M., Cimminiello, C., Csiba, L., Kaste, M., Leys, D., Rupprecht, H.J., Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): Randomised, double-blind, placebo-controlled trial (2004) Lancet, 364, pp. 331-337; Wiviott, S.D., Braunwald, E., Montalescot, G., Ruzyllo, W., Gottlieb, S., Neumann, F.J., Ardissino, D., Antman, E.M., TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes (2007) N Engl J Med, 357, pp. 2001-2015; Mehran, R., Rao, S.V., Bhatt, D.L., Gibson, C.M., Caixeta, A., Eikelboom, J., Kaul, S., White, H., Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the Bleeding Academic Research Consortium (2011) Circulation, 123, pp. 2736-2747; An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction (1993) N Engl J Med, 329, pp. 673-682; Diener, H.C., Bogousslavsky, J., Brass, L.M., Cimminiello, C., Csiba, L., Kaste, M., Leys, D., Rupprecht, H.J., Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke (MATCH): Study design and baseline data (2004) Cerebrovasc Dis, 17, pp. 253-261; (1997) Lancet, 349, pp. 1569-1581; Kennedy, J., Hill, M.D., Ryckborst, K.J., Eliasziw, M., Demchuk, A.M., Buchan, A.M., Fast Assessment of Stroke and Transient Ischaemic Attack to Prevent Early Recurrence (FASTER): A randomised controlled pilot trial (2007) Lancet Neurol, 6, pp. 961-969; Sacco, R.L., Diener, H.C., Yusuf, S., Cotton, D., Ounpuu, S., Lawton, W.A., Palesch, Y., Gu, V., Hermans son K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Vandermaelen C, Voigt T, Weber M, Yoon BW; PRo-FESS Study Group. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke (2008) N Engl J Med, 359, pp. 1238-1251; Wang, Y., Wang, Y., Zhao, X., Liu, L., Wang, D., Wang, C., Wang, C., Johnston, S.C., Clopidogrel with aspirin in acute minor stroke or transient ischemic attack (2013) N Engl J Med, 369, pp. 11-19; Morrow, D.A., Braunwald, E., Bonaca, M.P., Ameriso, S.F., Dalby, A.J., Fish, M.P., Fox, K.A., Murphy, S.A., TRA 2P-TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events (2012) N Engl J Med, 366, pp. 1404-1413",
year = "2017",
doi = "10.1161/CIRCULATIONAHA.117.028566",
language = "English",
volume = "136",
pages = "907--916",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Risk for major bleeding in patients receiving ticagrelor compared with aspirin after transient ischemic attack or acute ischemic stroke in the SOCRATES study (acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes)

AU - Easton, J.D.

AU - Aunes, M.

AU - Albers, G.W.

AU - Amarenco, P.

AU - Bokelund-Singh, S.

AU - Denison, H.

AU - Evans, S.R.

AU - Held, P.

AU - Jahreskog, M.

AU - Jonasson, J.

AU - Minematsu, K.

AU - Molina, C.A.

AU - Wang, Y.

AU - Wong, K.S.L.

AU - Johnston, S.C.

AU - Marcheselli, Simona

N1 - Cited By :1 Export Date: 2 March 2018 CODEN: CIRCA Correspondence Address: Johnston, S.C.; Dell Medical School, University of Texas at Austin, 1501 Red River St Stop ZO100, United States; email: clay.johnston@austin.utexas.edu Chemicals/CAS: acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1; ticagrelor, 274693-27-5; adenosine, 58-61-7; Adenosine; Aspirin; Purinergic P2Y Receptor Antagonists; Ticagrelor References: Husted, S., Emanuelsson, H., Heptinstall, S., Sandset, P.M., Wickens, M., Peters, G., Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: A double-blind comparison to clopidogrel with aspirin (2006) Eur Heart J, 27, pp. 1038-1047; Storey, R.F., Husted, S., Harrington, R.A., Heptinstall, S., Wilcox, R.G., Peters, G., Wickens, M., Cannon, C.P., Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes (2007) J Am Coll Cardiol, 50, p. 1852; Armstrong, D., Summers, C., Ewart, L., Nylander, S., Sidaway, J.E., Van Giezen, J.J., Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant inhibition of equilibrative nucleoside transporter 1 (2014) J Cardiovasc Pharmacol Ther, 19, pp. 209-219; James, S., Akerblom, A., Cannon, C.P., Emanuelsson, H., Husted, S., Katus, H., Skene, A., Wallentin, L., Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial (2009) Am Heart J, 157, p. 599; Wallentin, L., Becker, R.C., Budaj, A., Cannon, C.P., Emanuelsson, H., Held, C., Horrow, J., Thorsén, M., Ticagrelor versus clopidogrel in patients with acute coronary syndromes (2009) N Engl J Med, 361, pp. 1045-1057; Bonaca, M.P., Goto, S., Bhatt, D.L., Steg, P.G., Storey, R.F., Cohen, M., Goodrich, E., Ruda, M., (2016) Circulation, 134, pp. 861-871. , Morrow DA, Braunwald E, Sabatine MS. Prevention of stroke with ticagrelor in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54; Johnston, S.C., Amarenco, P., Albers, G.W., Denison, H., Easton, J.D., Evans, S.R., Held, P., Wong, K.S., And Investigators. Ticagrelor versus aspirin in acute stroke or transient ischemic attack (2016) N Engl J Med, 375, pp. 35-43; Johnston, S.C., Amarenco, P., Albers, G.W., Denison, H., Easton, J.D., Held, P., Jonasson, J., Wong, L.K., Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: Rationale and design (2015) Int J Stroke, 10, pp. 1304-1308; Serebruany, V.L., Steinhubl, S.R., Berger, P.B., Malinin, A.I., Baggish, J.S., Bhatt, D.L., Topol, E.J., Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials (2005) Am J Cardiol, 95, pp. 1218-1222; Diener, H.C., Bogousslavsky, J., Brass, L.M., Cimminiello, C., Csiba, L., Kaste, M., Leys, D., Rupprecht, H.J., Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): Randomised, double-blind, placebo-controlled trial (2004) Lancet, 364, pp. 331-337; Wiviott, S.D., Braunwald, E., Montalescot, G., Ruzyllo, W., Gottlieb, S., Neumann, F.J., Ardissino, D., Antman, E.M., TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes (2007) N Engl J Med, 357, pp. 2001-2015; Mehran, R., Rao, S.V., Bhatt, D.L., Gibson, C.M., Caixeta, A., Eikelboom, J., Kaul, S., White, H., Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the Bleeding Academic Research Consortium (2011) Circulation, 123, pp. 2736-2747; An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction (1993) N Engl J Med, 329, pp. 673-682; Diener, H.C., Bogousslavsky, J., Brass, L.M., Cimminiello, C., Csiba, L., Kaste, M., Leys, D., Rupprecht, H.J., Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke (MATCH): Study design and baseline data (2004) Cerebrovasc Dis, 17, pp. 253-261; (1997) Lancet, 349, pp. 1569-1581; Kennedy, J., Hill, M.D., Ryckborst, K.J., Eliasziw, M., Demchuk, A.M., Buchan, A.M., Fast Assessment of Stroke and Transient Ischaemic Attack to Prevent Early Recurrence (FASTER): A randomised controlled pilot trial (2007) Lancet Neurol, 6, pp. 961-969; Sacco, R.L., Diener, H.C., Yusuf, S., Cotton, D., Ounpuu, S., Lawton, W.A., Palesch, Y., Gu, V., Hermans son K, Hilbrich L, Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Vandermaelen C, Voigt T, Weber M, Yoon BW; PRo-FESS Study Group. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke (2008) N Engl J Med, 359, pp. 1238-1251; Wang, Y., Wang, Y., Zhao, X., Liu, L., Wang, D., Wang, C., Wang, C., Johnston, S.C., Clopidogrel with aspirin in acute minor stroke or transient ischemic attack (2013) N Engl J Med, 369, pp. 11-19; Morrow, D.A., Braunwald, E., Bonaca, M.P., Ameriso, S.F., Dalby, A.J., Fish, M.P., Fox, K.A., Murphy, S.A., TRA 2P-TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events (2012) N Engl J Med, 366, pp. 1404-1413

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. © 2017 American Heart Association, Inc.

AB - BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. © 2017 American Heart Association, Inc.

KW - Aspirin

KW - Hemorrhage

KW - Ischemic attack

KW - Platelet aggregation inhibitors

KW - Stroke

KW - Transient

KW - acetylsalicylic acid

KW - ticagrelor

KW - adenosine

KW - purinergic P2Y receptor antagonist

KW - aged

KW - aneurysm clipping

KW - angioplasty

KW - anticoagulant therapy

KW - aortic aneurysm

KW - Article

KW - brain artery aneurysm

KW - brain hemorrhage

KW - carotid artery stenting

KW - clinical trial

KW - decompressive craniectomy

KW - drug safety

KW - female

KW - gastrointestinal hemorrhage

KW - human

KW - internal carotid artery

KW - loading drug dose

KW - major clinical study

KW - male

KW - monotherapy

KW - patient safety

KW - percutaneous coronary intervention

KW - priority journal

KW - risk assessment

KW - thorax surgery

KW - thrombectomy

KW - transient ischemic attack

KW - treatment outcome

KW - analogs and derivatives

KW - bleeding

KW - chemically induced

KW - complication

KW - Ischemic Attack, Transient

KW - risk

KW - Adenosine

KW - Aged

KW - Female

KW - Humans

KW - Male

KW - Purinergic P2Y Receptor Antagonists

KW - Risk

KW - Treatment Outcome

U2 - 10.1161/CIRCULATIONAHA.117.028566

DO - 10.1161/CIRCULATIONAHA.117.028566

M3 - Article

VL - 136

SP - 907

EP - 916

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 10

ER -