Efficacy and safety of vorapaxar in patients with prior ischemic stroke

David A. Morrow, Mark J. Alberts, Jay P. Mohr, Sebastian F. Ameriso, Marc P. Bonaca, Shinya Goto, Graeme J. Hankey, Sabina A. Murphy, Benjamin M. Scirica, Eugene Braunwald

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background and Purpose-Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the proteaseactivated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods-We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. Results-The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46-4.36). Conclusions-In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.

Original languageEnglish (US)
Pages (from-to)691-698
Number of pages8
JournalStroke
Volume44
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

Stroke
Safety
Myocardial Infarction
Intracranial Hemorrhages
Placebos
Confidence Intervals
vorapaxar
Peripheral Arterial Disease
Platelet Aggregation Inhibitors
Thrombin
Blood Vessels
Therapeutics
Blood Platelets
Randomized Controlled Trials

Keywords

  • Clinical trial
  • Secondary prevention
  • Stroke
  • Thrombin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Morrow, D. A., Alberts, M. J., Mohr, J. P., Ameriso, S. F., Bonaca, M. P., Goto, S., ... Braunwald, E. (2013). Efficacy and safety of vorapaxar in patients with prior ischemic stroke. Stroke, 44(3), 691-698. https://doi.org/10.1161/STROKEAHA.111.000433

Efficacy and safety of vorapaxar in patients with prior ischemic stroke. / Morrow, David A.; Alberts, Mark J.; Mohr, Jay P.; Ameriso, Sebastian F.; Bonaca, Marc P.; Goto, Shinya; Hankey, Graeme J.; Murphy, Sabina A.; Scirica, Benjamin M.; Braunwald, Eugene.

In: Stroke, Vol. 44, No. 3, 03.2013, p. 691-698.

Research output: Contribution to journalArticle

Morrow, DA, Alberts, MJ, Mohr, JP, Ameriso, SF, Bonaca, MP, Goto, S, Hankey, GJ, Murphy, SA, Scirica, BM & Braunwald, E 2013, 'Efficacy and safety of vorapaxar in patients with prior ischemic stroke', Stroke, vol. 44, no. 3, pp. 691-698. https://doi.org/10.1161/STROKEAHA.111.000433
Morrow, David A. ; Alberts, Mark J. ; Mohr, Jay P. ; Ameriso, Sebastian F. ; Bonaca, Marc P. ; Goto, Shinya ; Hankey, Graeme J. ; Murphy, Sabina A. ; Scirica, Benjamin M. ; Braunwald, Eugene. / Efficacy and safety of vorapaxar in patients with prior ischemic stroke. In: Stroke. 2013 ; Vol. 44, No. 3. pp. 691-698.
@article{82e9f795409b4626a175943c88e7de30,
title = "Efficacy and safety of vorapaxar in patients with prior ischemic stroke",
abstract = "Background and Purpose-Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the proteaseactivated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods-We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. Results-The qualifying stroke was classified as large vessel in 35{\%}, small vessel in 47{\%}, and other/unknown in 18{\%}. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0{\%} vs 11.7{\%}; hazard ratio, 1.03; 95{\%} confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95{\%} confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5{\%} vs 1.0{\%}; hazard ratio, 2.52; 95{\%} confidence interval, 1.46-4.36). Conclusions-In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.",
keywords = "Clinical trial, Secondary prevention, Stroke, Thrombin",
author = "Morrow, {David A.} and Alberts, {Mark J.} and Mohr, {Jay P.} and Ameriso, {Sebastian F.} and Bonaca, {Marc P.} and Shinya Goto and Hankey, {Graeme J.} and Murphy, {Sabina A.} and Scirica, {Benjamin M.} and Eugene Braunwald",
year = "2013",
month = "3",
doi = "10.1161/STROKEAHA.111.000433",
language = "English (US)",
volume = "44",
pages = "691--698",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Efficacy and safety of vorapaxar in patients with prior ischemic stroke

AU - Morrow, David A.

AU - Alberts, Mark J.

AU - Mohr, Jay P.

AU - Ameriso, Sebastian F.

AU - Bonaca, Marc P.

AU - Goto, Shinya

AU - Hankey, Graeme J.

AU - Murphy, Sabina A.

AU - Scirica, Benjamin M.

AU - Braunwald, Eugene

PY - 2013/3

Y1 - 2013/3

N2 - Background and Purpose-Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the proteaseactivated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods-We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. Results-The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46-4.36). Conclusions-In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.

AB - Background and Purpose-Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the proteaseactivated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods-We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. Results-The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46-4.36). Conclusions-In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.

KW - Clinical trial

KW - Secondary prevention

KW - Stroke

KW - Thrombin

UR - http://www.scopus.com/inward/record.url?scp=84876282305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876282305&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.111.000433

DO - 10.1161/STROKEAHA.111.000433

M3 - Article

C2 - 23396280

AN - SCOPUS:84876282305

VL - 44

SP - 691

EP - 698

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 3

ER -