Effect of platelet inhibition with Cangrelor during PCI on ischemic events

Deepak L. Bhatt, Gregg W. Stone, Kenneth W. Mahaffey, C. Michael Gibson, P. Gabriel Steg, Christian W. Hamm, Matthew J. Price, Sergio Leonardi, Dianne Gallup, Ezio Bramucci, Peter W. Radke, Petr Widimský, Frantisek Tousek, Jeffrey Tauth, Douglas Spriggs, Brent T. McLaurin, Dominick J. Angiolillo, Philippe Genereux, Tiepu Liu, Jayne Prats & 4 others Meredith Todd, Simona Skerjanec, Harvey D. White, Robert A. Harrington

Research output: Contribution to journalArticle

470 Citations (Scopus)

Abstract

Background: The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. Methods: In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guidelinerecommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. Results: The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P = 0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P = 0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P = 0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. Conclusions: Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.)

Original languageEnglish (US)
Pages (from-to)1303-1313
Number of pages11
JournalNew England Journal of Medicine
Volume368
Issue number14
DOIs
StatePublished - Apr 4 2013
Externally publishedYes

Fingerprint

clopidogrel
Percutaneous Coronary Intervention
Blood Platelets
Stents
Thrombosis
Odds Ratio
Confidence Intervals
Purinergic P2Y Receptor Antagonists
Hemorrhage
Safety
cangrelor
Random Allocation
Dyspnea
Myocardial Ischemia
Therapeutics
Myocardial Infarction
Placebos
Medicine

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Bhatt, D. L., Stone, G. W., Mahaffey, K. W., Gibson, C. M., Steg, P. G., Hamm, C. W., ... Harrington, R. A. (2013). Effect of platelet inhibition with Cangrelor during PCI on ischemic events. New England Journal of Medicine, 368(14), 1303-1313. https://doi.org/10.1056/NEJMoa1300815
Bhatt, Deepak L. ; Stone, Gregg W. ; Mahaffey, Kenneth W. ; Gibson, C. Michael ; Steg, P. Gabriel ; Hamm, Christian W. ; Price, Matthew J. ; Leonardi, Sergio ; Gallup, Dianne ; Bramucci, Ezio ; Radke, Peter W. ; Widimský, Petr ; Tousek, Frantisek ; Tauth, Jeffrey ; Spriggs, Douglas ; McLaurin, Brent T. ; Angiolillo, Dominick J. ; Genereux, Philippe ; Liu, Tiepu ; Prats, Jayne ; Todd, Meredith ; Skerjanec, Simona ; White, Harvey D. ; Harrington, Robert A. / Effect of platelet inhibition with Cangrelor during PCI on ischemic events. In: New England Journal of Medicine. 2013 ; Vol. 368, No. 14. pp. 1303-1313.
@article{038f190697af4d7188b1cbaec0f19729,
title = "Effect of platelet inhibition with Cangrelor during PCI on ischemic events",
abstract = "Background: The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. Methods: In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guidelinerecommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. Results: The rate of the primary efficacy end point was 4.7{\%} in the cangrelor group and 5.9{\%} in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95{\%} confidence interval [CI], 0.66 to 0.93; P = 0.005). The rate of the primary safety end point was 0.16{\%} in the cangrelor group and 0.11{\%} in the clopidogrel group (odds ratio, 1.50; 95{\%} CI, 0.53 to 4.22; P = 0.44). Stent thrombosis developed in 0.8{\%} of the patients in the cangrelor group and in 1.4{\%} in the clopidogrel group (odds ratio, 0.62; 95{\%} CI, 0.43 to 0.90; P = 0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2{\%} vs. 0.3{\%}). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. Conclusions: Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.)",
author = "Bhatt, {Deepak L.} and Stone, {Gregg W.} and Mahaffey, {Kenneth W.} and Gibson, {C. Michael} and Steg, {P. Gabriel} and Hamm, {Christian W.} and Price, {Matthew J.} and Sergio Leonardi and Dianne Gallup and Ezio Bramucci and Radke, {Peter W.} and Petr Widimsk{\'y} and Frantisek Tousek and Jeffrey Tauth and Douglas Spriggs and McLaurin, {Brent T.} and Angiolillo, {Dominick J.} and Philippe Genereux and Tiepu Liu and Jayne Prats and Meredith Todd and Simona Skerjanec and White, {Harvey D.} and Harrington, {Robert A.}",
year = "2013",
month = "4",
day = "4",
doi = "10.1056/NEJMoa1300815",
language = "English (US)",
volume = "368",
pages = "1303--1313",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "14",

}

Bhatt, DL, Stone, GW, Mahaffey, KW, Gibson, CM, Steg, PG, Hamm, CW, Price, MJ, Leonardi, S, Gallup, D, Bramucci, E, Radke, PW, Widimský, P, Tousek, F, Tauth, J, Spriggs, D, McLaurin, BT, Angiolillo, DJ, Genereux, P, Liu, T, Prats, J, Todd, M, Skerjanec, S, White, HD & Harrington, RA 2013, 'Effect of platelet inhibition with Cangrelor during PCI on ischemic events', New England Journal of Medicine, vol. 368, no. 14, pp. 1303-1313. https://doi.org/10.1056/NEJMoa1300815

Effect of platelet inhibition with Cangrelor during PCI on ischemic events. / Bhatt, Deepak L.; Stone, Gregg W.; Mahaffey, Kenneth W.; Gibson, C. Michael; Steg, P. Gabriel; Hamm, Christian W.; Price, Matthew J.; Leonardi, Sergio; Gallup, Dianne; Bramucci, Ezio; Radke, Peter W.; Widimský, Petr; Tousek, Frantisek; Tauth, Jeffrey; Spriggs, Douglas; McLaurin, Brent T.; Angiolillo, Dominick J.; Genereux, Philippe; Liu, Tiepu; Prats, Jayne; Todd, Meredith; Skerjanec, Simona; White, Harvey D.; Harrington, Robert A.

In: New England Journal of Medicine, Vol. 368, No. 14, 04.04.2013, p. 1303-1313.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of platelet inhibition with Cangrelor during PCI on ischemic events

AU - Bhatt, Deepak L.

AU - Stone, Gregg W.

AU - Mahaffey, Kenneth W.

AU - Gibson, C. Michael

AU - Steg, P. Gabriel

AU - Hamm, Christian W.

AU - Price, Matthew J.

AU - Leonardi, Sergio

AU - Gallup, Dianne

AU - Bramucci, Ezio

AU - Radke, Peter W.

AU - Widimský, Petr

AU - Tousek, Frantisek

AU - Tauth, Jeffrey

AU - Spriggs, Douglas

AU - McLaurin, Brent T.

AU - Angiolillo, Dominick J.

AU - Genereux, Philippe

AU - Liu, Tiepu

AU - Prats, Jayne

AU - Todd, Meredith

AU - Skerjanec, Simona

AU - White, Harvey D.

AU - Harrington, Robert A.

PY - 2013/4/4

Y1 - 2013/4/4

N2 - Background: The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. Methods: In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guidelinerecommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. Results: The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P = 0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P = 0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P = 0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. Conclusions: Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.)

AB - Background: The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. Methods: In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guidelinerecommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. Results: The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P = 0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P = 0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P = 0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. Conclusions: Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.)

UR - http://www.scopus.com/inward/record.url?scp=84875779761&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875779761&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1300815

DO - 10.1056/NEJMoa1300815

M3 - Article

VL - 368

SP - 1303

EP - 1313

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 14

ER -

Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW et al. Effect of platelet inhibition with Cangrelor during PCI on ischemic events. New England Journal of Medicine. 2013 Apr 4;368(14):1303-1313. https://doi.org/10.1056/NEJMoa1300815