Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial)

Jan H. Cornel; Pierluigi Tricoci; Yuliya Lokhnygina; David J. Moliterno; Lars Wallentin; Paul W. Armstrong; Philip E. Aylward; Robert M. Clare; Edmond Chen; Sergio Leonardi; Frans Van De Werf; Harvey D. White; Claes Held; John Strony; Kenneth W. Mahaffey; Robert A. Harrington

doi:10.1016/j.amjcard.2015.02.043

Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial)

Jan H. Cornel
, Pierluigi Tricoci
, Yuliya Lokhnygina
, David J. Moliterno
, Lars Wallentin
, Paul W. Armstrong
, Philip E. Aylward
, Robert M. Clare
, Edmond Chen
, Sergio Leonardi
, Frans Van De Werf
, Harvey D. White
, Claes Held
, John Strony
, Kenneth W. Mahaffey
, Robert A. Harrington

Producción científica: Article › revisión exhaustiva

15 Citas (Scopus)

Resumen

We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIb/IIIa group; adjusted HR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

Idioma original	English
Páginas (desde-hasta)	1325-1332
Número de páginas	8
Publicación	American Journal of Cardiology
Volumen	115
N.º	10
DOI	https://doi.org/10.1016/j.amjcard.2015.02.043
Estado	Published - may 15 2015

Nota bibliográfica

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Financiación

The TRACER trial was supported by the Merck & Co., Inc. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the report, and its final contents. Dr. Cornel: Consulting fees/honorarium from AstraZeneca, Merck & Co., Eli Lilly, and Bristol-Myers Squibb/Pfizer; travel support from Bayer. Dr. Tricoci: Consultant agreement and research grant from Merck . Dr. Wallentin: Research grants from AstraZeneca , Merck , Boehringer Ingelheim , Bristol-Myers Squibb / Pfizer , and GlaxoSmithKline ; consultant for Abbott, Merck & Co., Regado Biosciences, Athera Biotechnologies, Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, and Bristol-Myers Squibb/Pfizer; lecture fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, and GlaxoSmithKline; honoraria from Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline; travel support from AstraZeneca, Bristol-Myers Squibb/Pfizer, and GSK. Dr. Armstrong: Research grant from Merck ; consulting for Eli Lilly; other for AstraZeneca. Dr. Aylward: Research grant, consulting fees/honorarium, and travel support from Merck & Co; grant support from Eli Lilly and Bayer J&J ; consultancy, lectures, and travel support from AstraZeneca and Boehringer Ingelheim; consultancy for Pfizer and Sanofi-Aventis; consultancy and lectures for Eli Lilly; and grants/pending grants from AstraZeneca . Dr. Chen: Former employee of Merck & Co., Inc. Dr. Van de Werf: Research grant, honoraria for lectures, and advisory board membership from Merck & Co. Dr. White: Grants from Sanofi-Aventis , Eli Lilly , The Medicines Company , NIH , Roche , Merck Sharpe & Dohme , AstraZeneca , GSK , and Daiichi Sankyo Pharma Development ; nonfinancial support from AstraZeneca, non-MSD, Roche, and Regado Biosciences outside the submitted work; Dr. Held: Institutional research grants from AstraZeneca , Merck , GlaxoSmithKline , Roche , and BMS / Pfizer ; advisory board for AstraZeneca; speaker honoraria from AstraZeneca. Dr. Strony: Employee of Merck & Co. Dr. Mahaffey: Grants from Merck during the conduct of the study; grants and personal fees from Merck & Co. outside the submitted work. Full disclosures before August 1, 2013, available at www.dcri.org . Disclosures after August 1, 2013, available at http://med.stanford.edu/profiles/kenneth_mahaffey . Dr. Harrington: Research grants and consultant/advisory fees from Merck & Co. Full disclosures available at http://med.stanford.edu/profiles/Robert_Harrington/ . Drs Lokhnygina, Moliterno, Leonardi, and Clare: None.

Financiadores
Daiichi Sankyo Pharma Development
National Institutes of Health (NIH)
Abbott Laboratories
Bristol-Myers Squibb
Eli Lilly and Company
Pfizer
AstraZeneca
GlaxoSmithKline
Merck
Roche Diagnostics
Boehringer-Ingelheim
Merck Sharp and Dohme

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Acceder al documento

10.1016/j.amjcard.2015.02.043

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Cornel, J. H., Tricoci, P., Lokhnygina, Y., Moliterno, D. J., Wallentin, L., Armstrong, P. W., Aylward, P. E., Clare, R. M., Chen, E., Leonardi, S., Van De Werf, F., White, H. D., Held, C., Strony, J., Mahaffey, K. W., & Harrington, R. A. (2015). Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial). American Journal of Cardiology, 115(10), 1325-1332. https://doi.org/10.1016/j.amjcard.2015.02.043

@article{d73cdb995d8f42019d463c838233f346,

title = "Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial)",

abstract = "We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1\%) received inhibitors and 5,432 (72.9\%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3\% vs 1.0\%) and did not (0.6\% vs 0.4\%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95\% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95\% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95\% CI 0.36 to 6.56 in the GP IIb/IIIa group; adjusted HR 1.34, 95\% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.",

author = "Cornel, \{Jan H.\} and Pierluigi Tricoci and Yuliya Lokhnygina and Moliterno, \{David J.\} and Lars Wallentin and Armstrong, \{Paul W.\} and Aylward, \{Philip E.\} and Clare, \{Robert M.\} and Edmond Chen and Sergio Leonardi and \{Van De Werf\}, Frans and White, \{Harvey D.\} and Claes Held and John Strony and Mahaffey, \{Kenneth W.\} and Harrington, \{Robert A.\}",

year = "2015",

month = may,

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Cornel, JH, Tricoci, P, Lokhnygina, Y, Moliterno, DJ, Wallentin, L, Armstrong, PW, Aylward, PE, Clare, RM, Chen, E, Leonardi, S, Van De Werf, F, White, HD, Held, C, Strony, J, Mahaffey, KW & Harrington, RA 2015, 'Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial)', American Journal of Cardiology, vol. 115, n.º 10, pp. 1325-1332. https://doi.org/10.1016/j.amjcard.2015.02.043

Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial). / Cornel, Jan H.; Tricoci, Pierluigi; Lokhnygina, Yuliya et al.
En: American Journal of Cardiology, Vol. 115, N.º 10, 15.05.2015, p. 1325-1332.

Producción científica: Article › revisión exhaustiva

TY - JOUR

T1 - Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial)

AU - Cornel, Jan H.

AU - Tricoci, Pierluigi

AU - Lokhnygina, Yuliya

AU - Moliterno, David J.

AU - Wallentin, Lars

AU - Armstrong, Paul W.

AU - Aylward, Philip E.

AU - Clare, Robert M.

AU - Chen, Edmond

AU - Leonardi, Sergio

AU - Van De Werf, Frans

AU - White, Harvey D.

AU - Held, Claes

AU - Strony, John

AU - Mahaffey, Kenneth W.

AU - Harrington, Robert A.

PY - 2015/5/15

Y1 - 2015/5/15

N2 - We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIb/IIIa group; adjusted HR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

AB - We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIb/IIIa group; adjusted HR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

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Cornel JH, Tricoci P, Lokhnygina Y, Moliterno DJ, Wallentin L, Armstrong PW et al. Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER trial). American Journal of Cardiology. 2015 may 15;115(10):1325-1332. doi: 10.1016/j.amjcard.2015.02.043