Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack

Stefan K. James, Robert F. Storey, Nardev S. Khurmi, Steen Husted, M. Keltai, Kenneth W. Mahaffey, Juan Maya, Joao Morais, Renato D. Lopes, Jose C. Nicolau, Prem Pais, Dimitar Raev, Jose L. Lopez-Sendon, Susanna R. Stevens, Richard C. Becker

Research output: Contribution to journalArticle

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Abstract

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality. Clinical Trial Registration-URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Original languageEnglish
Pages (from-to)2914-2921
Number of pages8
JournalCirculation
Volume125
Issue number23
DOIs
Publication statusPublished - Jun 12 2012

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clopidogrel
Transient Ischemic Attack
Acute Coronary Syndrome
Stroke
Hemorrhage
Confidence Intervals
Ticagrelor
Mortality
Intracranial Hemorrhages

Keywords

  • acute coronary syndrome
  • antiplatelet drugs
  • cardiovascular diseases
  • stroke
  • ticagrelor

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack. / James, Stefan K.; Storey, Robert F.; Khurmi, Nardev S.; Husted, Steen; Keltai, M.; Mahaffey, Kenneth W.; Maya, Juan; Morais, Joao; Lopes, Renato D.; Nicolau, Jose C.; Pais, Prem; Raev, Dimitar; Lopez-Sendon, Jose L.; Stevens, Susanna R.; Becker, Richard C.

In: Circulation, Vol. 125, No. 23, 12.06.2012, p. 2914-2921.

Research output: Contribution to journalArticle

James, SK, Storey, RF, Khurmi, NS, Husted, S, Keltai, M, Mahaffey, KW, Maya, J, Morais, J, Lopes, RD, Nicolau, JC, Pais, P, Raev, D, Lopez-Sendon, JL, Stevens, SR & Becker, RC 2012, 'Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack', Circulation, vol. 125, no. 23, pp. 2914-2921. https://doi.org/10.1161/CIRCULATIONAHA.111.082727
James, Stefan K. ; Storey, Robert F. ; Khurmi, Nardev S. ; Husted, Steen ; Keltai, M. ; Mahaffey, Kenneth W. ; Maya, Juan ; Morais, Joao ; Lopes, Renato D. ; Nicolau, Jose C. ; Pais, Prem ; Raev, Dimitar ; Lopez-Sendon, Jose L. ; Stevens, Susanna R. ; Becker, Richard C. / Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack. In: Circulation. 2012 ; Vol. 125, No. 23. pp. 2914-2921.
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abstract = "Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2{\%}) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5{\%} versus 6.0{\%}), death (10.5{\%} versus 4.9{\%}), stroke (3.4{\%} versus 1.2{\%}), and intracranial bleeding (0.8{\%} versus 0.2{\%}) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0{\%} versus 20.8{\%} (hazard ratio, 0.87; 95{\%} confidence interval, 0.66-1.13; interaction P=0.84) and 7.9{\%} versus 13.0{\%} (hazard ratio, 0.62; 95{\%} confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6{\%} versus 14.9{\%} (hazard ratio, 0.99; 95{\%} confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality. Clinical Trial Registration-URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.",
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T1 - Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack

AU - James, Stefan K.

AU - Storey, Robert F.

AU - Khurmi, Nardev S.

AU - Husted, Steen

AU - Keltai, M.

AU - Mahaffey, Kenneth W.

AU - Maya, Juan

AU - Morais, Joao

AU - Lopes, Renato D.

AU - Nicolau, Jose C.

AU - Pais, Prem

AU - Raev, Dimitar

AU - Lopez-Sendon, Jose L.

AU - Stevens, Susanna R.

AU - Becker, Richard C.

PY - 2012/6/12

Y1 - 2012/6/12

N2 - Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality. Clinical Trial Registration-URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

AB - Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality. Clinical Trial Registration-URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

KW - acute coronary syndrome

KW - antiplatelet drugs

KW - cardiovascular diseases

KW - stroke

KW - ticagrelor

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