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Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial.

Publication ,  Journal Article
Angiolillo, DJ; Firstenberg, MS; Price, MJ; Tummala, PE; Hutyra, M; Welsby, IJ; Voeltz, MD; Chandna, H; Ramaiah, C; Brtko, M; Cannon, L ...
Published in: JAMA
January 18, 2012

CONTEXT: Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding. OBJECTIVE: To evaluate the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery. DESIGN, SETTING, AND PATIENTS: Prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery. MAIN OUTCOME MEASURES: The primary efficacy end point was platelet reactivity (measured in P2Y(12) reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery-related bleeding. RESULTS: The dose of cangrelor determined in 10 patients in the open-label stage was 0.75 μg/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery-related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor. CONCLUSIONS: Among patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00767507.

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Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

January 18, 2012

Volume

307

Issue

3

Start / End Page

265 / 274

Location

United States

Related Subject Headings

  • Thrombosis
  • Thienopyridines
  • Stents
  • Purinergic P2Y Receptor Antagonists
  • Postoperative Hemorrhage
  • Platelet Aggregation Inhibitors
  • Platelet Activation
  • Middle Aged
  • Male
  • Humans
 

Citation

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Angiolillo, D. J., Firstenberg, M. S., Price, M. J., Tummala, P. E., Hutyra, M., Welsby, I. J., … BRIDGE Investigators, . (2012). Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA, 307(3), 265–274. https://doi.org/10.1001/jama.2011.2002
Angiolillo, Dominick J., Michael S. Firstenberg, Matthew J. Price, Pradyumna E. Tummala, Martin Hutyra, Ian J. Welsby, Michele D. Voeltz, et al. “Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial.JAMA 307, no. 3 (January 18, 2012): 265–74. https://doi.org/10.1001/jama.2011.2002.
Angiolillo DJ, Firstenberg MS, Price MJ, Tummala PE, Hutyra M, Welsby IJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012 Jan 18;307(3):265–74.
Angiolillo, Dominick J., et al. “Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial.JAMA, vol. 307, no. 3, Jan. 2012, pp. 265–74. Pubmed, doi:10.1001/jama.2011.2002.
Angiolillo DJ, Firstenberg MS, Price MJ, Tummala PE, Hutyra M, Welsby IJ, Voeltz MD, Chandna H, Ramaiah C, Brtko M, Cannon L, Dyke C, Liu T, Montalescot G, Manoukian SV, Prats J, Topol EJ, BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012 Jan 18;307(3):265–274.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

January 18, 2012

Volume

307

Issue

3

Start / End Page

265 / 274

Location

United States

Related Subject Headings

  • Thrombosis
  • Thienopyridines
  • Stents
  • Purinergic P2Y Receptor Antagonists
  • Postoperative Hemorrhage
  • Platelet Aggregation Inhibitors
  • Platelet Activation
  • Middle Aged
  • Male
  • Humans