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Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery
Dominick J. Angiolillo,Michael S. Firstenberg,Matthew J. Price,Pradyumna E. Tummala,Martin Hutyra,Ian J. Welsby,Michele D. Voeltz,Harish Chandna,Chandrashekhar Ramaiah,Miroslav Brtko,Louis Cannon,Cornelius M. Dyke,Tiepu Liu,Gilles Montalescot,Steven V. Manoukian,Jayne Prats,Eric J. Topol +16 more
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TLDR
Cagalj et al. as discussed by the authors evaluated the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery.Abstract:
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.read more
Citations
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ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation
Stefan James,Dan Atar,Luigi P. Badano,Carina Blomström Lundqvist,Michael A. Borger,Anthony H. Gershlick,Kurt Huber,Peter Jüni,Mattie J. Lenzen,Kenneth W. Mahaffey,Marco Valgimigli +10 more
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Stephan Windecker,Philippe Kolh,Fernando Alfonso,Jean-Philippe Collet,Jochen Cremer,Volkmar Falk,Gerasimos Filippatos,Christian W. Hamm,Stuart J. Head,Peter Jüni,A. Pieter Kappetein,Adnan Kastrati,Juhani Knuuti,Ulf Landmesser,Günther Laufer,Franz-Josef Neumann,Dimitrios J. Richter,Patrick Schauerte,Miguel Sousa Uva,Giulio G. Stefanini,David P. Taggart,Lucia Torracca,Marco Valgimigli,William Wijns,Adam Witkowski +24 more
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2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS
Marco Valgimigli,Héctor Bueno,Robert A. Byrne,Jean-Philippe Collet,Francesco Costa,Anders Jeppsson,Peter Jüni,Adnan Kastrati,Philippe Kolh,Laura Mauri,Gilles Montalescot,Franz-Josef Neumann,Mate Petricevic,Marco Roffi,Philippe Gabriel Steg,Stephan Windecker,José Luis Zamorano,Glenn N. Levine,Lina Badimon,Pascal Vranckx,Stefan Agewall,Felicita Andreotti,Elliott M. Antman,Emanuele Barbato,Jean-Pierre Bassand,Raffaele Bugiardini,Mustafa Cikirikcioglu,Thomas Cuisset,Michele De Bonis,Victora Delgado,Donna Fitzsimons,Oliver Gaemperli,Nazzareno Galiè,Martine Gilard,Christian W. Hamm,Borja Ibanez,Bernard Iung,Stefan James,Juhani Knuuti,Ulf Landmesser,Christophe Leclercq,Maddalena Lettino,Gregory Y.H. Lip,Massimo F Piepoli,Luc Pierard,Markus Schwerzmann,Udo Sechtem,Iain A. Simpson,Miguel Sousa Uva,Eugenio Stabile,Robert F. Storey,Michal Tendera,Frans Van de Werf,Freek W.A. Verheugt,Victor Aboyans +54 more
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2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA).
Steen Dalby Kristensen,Juhani Knuuti,Antti Saraste,Stefan D. Anker,Hans Erik Bøtker,Stefan De Hert,Ian Ford,José Ramón González-Juanatey,Bulent Gorenek,Guy R. Heyndrickx,Andreas Hoeft,Kurt Huber,Bernard Iung,Keld Kjeldsen,Dan Longrois,Thomas F. Lüscher,Luc Pierard,Stuart J. Pocock,Susanna Price,Marco Roffi,Per Anton Sirnes,Miguel Sousa-Uva,Vasilis Voudris,Christian Funck-Brentano +23 more
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2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Glenn N. Levine,Eric R. Bates,John A. Bittl,Ralph G. Brindis,Stephan D. Fihn,Lee A. Fleisher,Christopher B. Granger,Richard A. Lange,Michael J. Mack,Laura Mauri,Roxana Mehran,Debabrata Mukherjee,L. Kristin Newby,Patrick T. O'Gara,Marc S. Sabatine,Peter K. Smith,Sidney C. Smith +16 more
TL;DR: Jonathan L. Halperin, MD, FACC, FAHA, Chair Glenn N. Levine, MD; Sana M. Al-Khatib,MD; and Lesley H. Curtis, PhD, PhD are the current members of the FACC/FAHA Board of Directors.
References
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