Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX

Matthew A Cavender, Robert A Harrington, Gregg W Stone, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Renato D Lopes, Sergio Leonardi, Efthymios N Deliargyris, Jayne Prats, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt, CHAMPION PHOENIX Investigators*, Robert A Harrington, Kurt Huber, Valter C Lima, Julia B Jorgova-Makedonska, Petr Widimský, Bondo Kobulia, Peter W Radke, Ezio Bramucci, Adam Witkowski, Evgeny Shlyakhto, Frans Van de Werf, David P Faxon, E Magnus Ohman, Freek W A Verheugt, W Douglas Weaver, Jan G P Tijssen, Matthew Wilson, Stacey Mangum, Chiara Melloni, Matthew J Brennan, Pierluigi Tricoci, Robert Harrison, Pedro Barros, Luciana Armaganijan, Monique Anderson, Akshay Bagai, Philippe Généreux, Sorin J Brener, Laura LaSalle, Werner Benzer, Georg Delle-Karth, Kurt Huber, Franz Leisch, Jamil Abdalla Saad, Alexandre Abizaid, Carlos Augusto Formiga Areas, Expedito E Ribeiro, Fabio Rossi Dos Santos, Rogerio Tadeu Tumelero, Roberto Vieira Botelho, Borislav Atzev, Boicho Boichev, Georgi Grigorov, Nikolay Penkov, Ivo Petrov, Boris Zehirov, Pavel Cervinka, Zdenek Coufal, Petr Hajek, David Horak, Petr Kala, Petr Kmonicek, Viktor Kocka, Jan Mrozek, Stanislav Simek, Jan Sitar, Josef Stasek, Frantisek Tousek, Gulnara Chapidze, Nodar Emukhvari, George Khabeishvili, Merab Mamatsashvili, Tamaz Shaburishvili, Steffen Behrens, Harald Darius, Martin Dissmann, Stephan Fichtlscherer, Wolfgang Franz, Tobias Geisler, Sabine Genth-Zotz, Britta Goldmann, Hubertus Heuer, Stefan Hoffmann, Andreas Mugge, Tudor Poerner, Peter Radke, Gert Richardt, Christoph Stellbrink, Nikos Werner, Ezio Bramucci, Stefano De Servi, Gennaro Galasso, Alberto Menozzi, Giuseppe Musumeci, Andrea Picchi, Patrizia Presbitero, Gerard Devlin, Alexander Sasse, Douglas Scott, Ralph Stewart, Szyszka Andrzej, Witold Dubaniewicz, Zbigniew Gasior, Jaroslaw Kasprzak, Andrzej Kleinrok, Zdzislawa Kornacewicz-Jach, Andrzej Rynkiewicz, Cezary Sosnowski, Radoslaw Targonski, Jaroslaw Trebacz, Adam Witkowski, Elzbieta Zinka, Olga Barbarash, Yakov Dovgalevsky, Ivan Gordeev, Svetlana Kalinina, Elena Kosmachova, Valentin Markov, Prokhor Pavlov, Sergey Shalaev, Zaur Shogenov, Irina Sukmanova, Elena Vasilieva, Alexey Yakovlev, Sarana Boonbaichaiyapruck, Noppadol Chamnarnphol, Pinij Kaewsuwanna, Srun Kuanprasert, Dilok Piyayotai, Maged Amine, Dominick Angiolillo, Imran Arif, James Blankenship, Emmanouil Brilakis, Michael Chan, Joseph Cinderella, Brent Davis, Chandanreddy Devireddy, Mark Dorogy, John Douglas, Norman Ferrier, Daniel Fisher, Robert Foster, William French, John Galla, Lawrence Gimple, Harinder Gogia, Prospero Gogo, Raghava Gollapudi, Luis Gruberg, James Hermiller, Richard Heuser, Robert Iwaoka, Zubair Jafar, Carey Kimmelstiel, Scott Kinlay, James Leggett, Pierre Leimgruber, Dustin Letts, Michael Lipsitt, Reginald Low, Joaquin Martinez-Arraras, Marc Mayhew, Brent McLaurin, Paul McWhirter, Ayoub Mirza, Brian Negus, Thomas Nygaard, William O'Riordan, Richard Paulus, John Petersen, Hector Picon, Mark Picone, Ernesto Rivera, David Rizik, David Rizik, Arsenio Rodriguez, Jorge Saucedo, J Christopher Scott, Virender Sethi, Adhir Shroff, Craig Siegel, Douglas Spriggs, Daniel Steinberg, Michael Stillabower, Thomas Stuckey, Jose Suarez, Jeffrey Tauth, Dogan Temizer, Mladen Vidovich, Michele Voeltz, Jonathan Waltman, Michael Wilensky, Matthew A Cavender, Robert A Harrington, Gregg W Stone, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Renato D Lopes, Sergio Leonardi, Efthymios N Deliargyris, Jayne Prats, Kenneth W Mahaffey, Harvey D White, Deepak L Bhatt, CHAMPION PHOENIX Investigators*, Robert A Harrington, Kurt Huber, Valter C Lima, Julia B Jorgova-Makedonska, Petr Widimský, Bondo Kobulia, Peter W Radke, Ezio Bramucci, Adam Witkowski, Evgeny Shlyakhto, Frans Van de Werf, David P Faxon, E Magnus Ohman, Freek W A Verheugt, W Douglas Weaver, Jan G P Tijssen, Matthew Wilson, Stacey Mangum, Chiara Melloni, Matthew J Brennan, Pierluigi Tricoci, Robert Harrison, Pedro Barros, Luciana Armaganijan, Monique Anderson, Akshay Bagai, Philippe Généreux, Sorin J Brener, Laura LaSalle, Werner Benzer, Georg Delle-Karth, Kurt Huber, Franz Leisch, Jamil Abdalla Saad, Alexandre Abizaid, Carlos Augusto Formiga Areas, Expedito E Ribeiro, Fabio Rossi Dos Santos, Rogerio Tadeu Tumelero, Roberto Vieira Botelho, Borislav Atzev, Boicho Boichev, Georgi Grigorov, Nikolay Penkov, Ivo Petrov, Boris Zehirov, Pavel Cervinka, Zdenek Coufal, Petr Hajek, David Horak, Petr Kala, Petr Kmonicek, Viktor Kocka, Jan Mrozek, Stanislav Simek, Jan Sitar, Josef Stasek, Frantisek Tousek, Gulnara Chapidze, Nodar Emukhvari, George Khabeishvili, Merab Mamatsashvili, Tamaz Shaburishvili, Steffen Behrens, Harald Darius, Martin Dissmann, Stephan Fichtlscherer, Wolfgang Franz, Tobias Geisler, Sabine Genth-Zotz, Britta Goldmann, Hubertus Heuer, Stefan Hoffmann, Andreas Mugge, Tudor Poerner, Peter Radke, Gert Richardt, Christoph Stellbrink, Nikos Werner, Ezio Bramucci, Stefano De Servi, Gennaro Galasso, Alberto Menozzi, Giuseppe Musumeci, Andrea Picchi, Patrizia Presbitero, Gerard Devlin, Alexander Sasse, Douglas Scott, Ralph Stewart, Szyszka Andrzej, Witold Dubaniewicz, Zbigniew Gasior, Jaroslaw Kasprzak, Andrzej Kleinrok, Zdzislawa Kornacewicz-Jach, Andrzej Rynkiewicz, Cezary Sosnowski, Radoslaw Targonski, Jaroslaw Trebacz, Adam Witkowski, Elzbieta Zinka, Olga Barbarash, Yakov Dovgalevsky, Ivan Gordeev, Svetlana Kalinina, Elena Kosmachova, Valentin Markov, Prokhor Pavlov, Sergey Shalaev, Zaur Shogenov, Irina Sukmanova, Elena Vasilieva, Alexey Yakovlev, Sarana Boonbaichaiyapruck, Noppadol Chamnarnphol, Pinij Kaewsuwanna, Srun Kuanprasert, Dilok Piyayotai, Maged Amine, Dominick Angiolillo, Imran Arif, James Blankenship, Emmanouil Brilakis, Michael Chan, Joseph Cinderella, Brent Davis, Chandanreddy Devireddy, Mark Dorogy, John Douglas, Norman Ferrier, Daniel Fisher, Robert Foster, William French, John Galla, Lawrence Gimple, Harinder Gogia, Prospero Gogo, Raghava Gollapudi, Luis Gruberg, James Hermiller, Richard Heuser, Robert Iwaoka, Zubair Jafar, Carey Kimmelstiel, Scott Kinlay, James Leggett, Pierre Leimgruber, Dustin Letts, Michael Lipsitt, Reginald Low, Joaquin Martinez-Arraras, Marc Mayhew, Brent McLaurin, Paul McWhirter, Ayoub Mirza, Brian Negus, Thomas Nygaard, William O'Riordan, Richard Paulus, John Petersen, Hector Picon, Mark Picone, Ernesto Rivera, David Rizik, David Rizik, Arsenio Rodriguez, Jorge Saucedo, J Christopher Scott, Virender Sethi, Adhir Shroff, Craig Siegel, Douglas Spriggs, Daniel Steinberg, Michael Stillabower, Thomas Stuckey, Jose Suarez, Jeffrey Tauth, Dogan Temizer, Mladen Vidovich, Michele Voeltz, Jonathan Waltman, Michael Wilensky

Abstract

Background: Thrombotic events are reduced with cangrelor, an intravenous P2Y12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention).

Methods: CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis).

Results: The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64-0.90], P=0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40-0.80], P=0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71-1.93]; P=0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37-5.40]; P=0.62).

Conclusions: The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01156571.

Keywords: P2Y12 receptor antagonist; coronary artery disease; myocardial infarction; percutaneous coronary intervention; thrombosis.

Figures

Figure 1.
Figure 1.
Landmark analyses of composite ischemic end points. Landmark analysis of the (A) incidence of death, myocardial infarction, ischemia driven revascularization, or stent thrombosis at 2 hr following randomization and after 2 hr and (B) death, myocardial infarction [Society of Angiography and Intervention], ischemia driven revascularization, or Academic Research Consortium stent thrombosis at 2 hr following randomization and after 2 hr. HR indicates hazard ratio.
Figure 2.
Figure 2.
Landmark analyses of individual ischemic end points. Landmark analysis of the incidence of (A) myocardial infarction (Society of Angiography and Intervention Definition) before and after 2 hr postrandomization and (B) stent thrombosis at 2 hr. HR indicates hazard ratio.
Figure 3.
Figure 3.
Distribution and type of ischemic events post-percutaneous coronary intervention in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). ARC indicates Academic Research Consortium; IDR, ischemia driven revascularization; MI, myocardial infarction; SCAI, Society of Angiography and Intervention; and ST, stent thrombosis.

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