Association of aspirin dose and vorapaxar safety and efficacy in patients with non-st-segment elevation acute coronary syndrome (from the tracer trial)

Kenneth W. Mahaffey, Zhen Huang, Lars Wallentin, Robert F. Storey, Lisa K. Jennings, Pierluigi Tricoci, Harvey D. White, Paul W. Armstrong, Philip E. Aylward, David J. Moliterno, Frans Van De Werf, Edmond Chen, Sergio Leonardi, Tyrus Rorick, Claes Held, John Strony, Robert A. Harrington

Research output: Contribution to journalArticle

Abstract

Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial compared vorapaxar and placebo in 12,944 high-risk patients with non-ST-segment elevation acute coronary syndrome. We explored aspirin (ASA) use and its association with outcomes. Kaplan-Meier event rates were compared in groups defined by ASA dose (low, medium, and high). Landmark analyses with covariate adjustment were performed for 0 to 30, 31 to 180, and 181 to 365 days. Of 12,515 participants, 7,523, 1,049, and 3,943 participants were treated with low-, medium-, and high-dose ASA at baseline, respectively. Participants enrolled in North America versus elsewhere were more often treated with a high dose at baseline (66% vs 19%) and discharge (60% vs 3%). Unadjusted cardiovascular death, myocardial infarction, stroke, hospitalization for ischemia, or urgent revascularization event rates tended to be higher with higher baseline ASA (18.45% low, 19.13% medium, and 20.27% high; p for trend = 0.15573). Unadjusted and adjusted hazard ratios (95% confidence intervals) for effect of vorapaxar on cardiovascular (unadjusted p for interaction = 0.065; adjusted p for interaction = 0.140) and bleeding (unadjusted p for interaction = 0.915; adjusted p for interaction = 0.954) outcomes were similar across groups. Landmark analyses showed similar safety and efficacy outcomes with vorapaxar and placebo by ASA dose at each time point except for 0 to 30 days, when vorapaxar tended to be worse for efficacy (hazard ratio 1.13, 95% confidence interval 0.89 to 1.44, p for interaction = 0.0157). In conclusion, most TRACER participants were treated with low-dose ASA, although a high dose was common in North America. High-dose participants tended to have higher rates of ischemic and bleeding outcomes. Although formal statistical testing did not reveal heterogeneity in vorapaxar's effect across dose subgroups, consistent trends support use of low-dose ASA with other antiplatelet therapies.

Original languageEnglish
Pages (from-to)936-944
Number of pages9
JournalThe American Journal of Cardiology
Volume113
Issue number6
DOIs
Publication statusPublished - Mar 15 2014

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Acute Coronary Syndrome
Aspirin
Safety
North America
Placebos
Confidence Intervals
Hemorrhage
Thrombin Receptors
Hospitalization
Ischemia
Stroke
Myocardial Infarction
vorapaxar
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Association of aspirin dose and vorapaxar safety and efficacy in patients with non-st-segment elevation acute coronary syndrome (from the tracer trial). / Mahaffey, Kenneth W.; Huang, Zhen; Wallentin, Lars; Storey, Robert F.; Jennings, Lisa K.; Tricoci, Pierluigi; White, Harvey D.; Armstrong, Paul W.; Aylward, Philip E.; Moliterno, David J.; Van De Werf, Frans; Chen, Edmond; Leonardi, Sergio; Rorick, Tyrus; Held, Claes; Strony, John; Harrington, Robert A.

In: The American Journal of Cardiology, Vol. 113, No. 6, 15.03.2014, p. 936-944.

Research output: Contribution to journalArticle

Mahaffey, KW, Huang, Z, Wallentin, L, Storey, RF, Jennings, LK, Tricoci, P, White, HD, Armstrong, PW, Aylward, PE, Moliterno, DJ, Van De Werf, F, Chen, E, Leonardi, S, Rorick, T, Held, C, Strony, J & Harrington, RA 2014, 'Association of aspirin dose and vorapaxar safety and efficacy in patients with non-st-segment elevation acute coronary syndrome (from the tracer trial)', The American Journal of Cardiology, vol. 113, no. 6, pp. 936-944. https://doi.org/10.1016/j.amjcard.2013.11.052
Mahaffey, Kenneth W. ; Huang, Zhen ; Wallentin, Lars ; Storey, Robert F. ; Jennings, Lisa K. ; Tricoci, Pierluigi ; White, Harvey D. ; Armstrong, Paul W. ; Aylward, Philip E. ; Moliterno, David J. ; Van De Werf, Frans ; Chen, Edmond ; Leonardi, Sergio ; Rorick, Tyrus ; Held, Claes ; Strony, John ; Harrington, Robert A. / Association of aspirin dose and vorapaxar safety and efficacy in patients with non-st-segment elevation acute coronary syndrome (from the tracer trial). In: The American Journal of Cardiology. 2014 ; Vol. 113, No. 6. pp. 936-944.
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AU - Storey, Robert F.

AU - Jennings, Lisa K.

AU - Tricoci, Pierluigi

AU - White, Harvey D.

AU - Armstrong, Paul W.

AU - Aylward, Philip E.

AU - Moliterno, David J.

AU - Van De Werf, Frans

AU - Chen, Edmond

AU - Leonardi, Sergio

AU - Rorick, Tyrus

AU - Held, Claes

AU - Strony, John

AU - Harrington, Robert A.

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N2 - Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial compared vorapaxar and placebo in 12,944 high-risk patients with non-ST-segment elevation acute coronary syndrome. We explored aspirin (ASA) use and its association with outcomes. Kaplan-Meier event rates were compared in groups defined by ASA dose (low, medium, and high). Landmark analyses with covariate adjustment were performed for 0 to 30, 31 to 180, and 181 to 365 days. Of 12,515 participants, 7,523, 1,049, and 3,943 participants were treated with low-, medium-, and high-dose ASA at baseline, respectively. Participants enrolled in North America versus elsewhere were more often treated with a high dose at baseline (66% vs 19%) and discharge (60% vs 3%). Unadjusted cardiovascular death, myocardial infarction, stroke, hospitalization for ischemia, or urgent revascularization event rates tended to be higher with higher baseline ASA (18.45% low, 19.13% medium, and 20.27% high; p for trend = 0.15573). Unadjusted and adjusted hazard ratios (95% confidence intervals) for effect of vorapaxar on cardiovascular (unadjusted p for interaction = 0.065; adjusted p for interaction = 0.140) and bleeding (unadjusted p for interaction = 0.915; adjusted p for interaction = 0.954) outcomes were similar across groups. Landmark analyses showed similar safety and efficacy outcomes with vorapaxar and placebo by ASA dose at each time point except for 0 to 30 days, when vorapaxar tended to be worse for efficacy (hazard ratio 1.13, 95% confidence interval 0.89 to 1.44, p for interaction = 0.0157). In conclusion, most TRACER participants were treated with low-dose ASA, although a high dose was common in North America. High-dose participants tended to have higher rates of ischemic and bleeding outcomes. Although formal statistical testing did not reveal heterogeneity in vorapaxar's effect across dose subgroups, consistent trends support use of low-dose ASA with other antiplatelet therapies.

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