Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention

Core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial

Gregg W. Stone, Philippe Genereux, Robert A. Harrington, Harvey D. White, C. Michael Gibson, P. Gabriel Steg, Christian W. Hamm, Kenneth W. Mahaffey, Matthew J. Price, Jayne Prats, Efthymios N. Deliargyris, Deepak L. Bhatt

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aims In the CHAMPION PHOENIX trial, the potent, rapidly acting, intravenous platelet adenosine diphosphate receptor antagonist cangrelor reduced the 48-h incidence of major adverse cardiac events (MACE; death, myocardial infarction, stent thrombosis, or ischaemia-driven revascularization) compared with a loading dose of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We sought to determine whether the efficacy of cangrelor during PCI varies in patients with simple vs. complex target lesion coronary anatomy. Methods and results Blinded angiographic core laboratory analysis was completed in 10 854 of 10 942 (99.2%) randomized patients in CHAMPION PHOENIX (13 418 target lesions). Outcomes were analysed according to the number of angiographic PCI target lesion high-risk features (HRF) present (bifurcation, left main, thrombus, angulated, tortuous, eccentric, calcified, long, or multi-lesion treatment). The number of patients with 0, 1, 2, and ≥3 HRFs was 1817 (16.7%), 3442 (31.7%), 2901 (26.7%), and 2694 (24.8%), respectively. The 48-h MACE rate in clopidogrel-treated patients increased progressively with lesion complexity (from 3.3% to 4.4% to 6.9% to 8.7%, respectively, P < 0.0001). Cangrelor reduced the 48-h rate of MACE by 21% {4.7% vs. 5.9%, odds ratio (OR) [95% confidence interval (95% CI)] 0.79 (0.67, 0.93), P = 0.006} compared with clopidogrel, an effect which was consistent regardless of PCI lesion complexity (Pinteraction = 0.66) and presentation with stable ischaemic heart disease (SIHD) or an acute coronary syndrome (ACS). By multivariable analysis, the number of high-risk PCI characteristics [OR (95% CI) 1.68 (1.20, 2.36), 2.78 (2.00, 3.87), and 3.23 (2.33, 4.48) for 1, 2, and 3 HRFs compared with 0 HRFs, all P < 0.0001] and treatment with cangrelor vs. clopidogrel [OR (95% CI) 0.78 (0.66, 0.92), P = 0.004] were independent predictors of the primary 48-h MACE endpoint. Major bleeding rates were unrelated to lesion complexity and were not increased by cangrelor. Conclusion Peri-procedural MACE after PCI is strongly dependent on the number of treated high-risk target lesion features. Compared with a loading dose of clopidogrel, cangrelor reduced MACE occurring within 48 h after PCI in patients with SIHD and ACS regardless of baseline lesion complexity. The absolute benefit:risk profile for cangrelor will therefore be greatest during PCI in patients with complex coronary anatomy.

Original languageEnglish (US)
Pages (from-to)4112-4121
Number of pages10
JournalEuropean Heart Journal
Volume39
Issue number46
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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clopidogrel
Purinergic P1 Receptors
Percutaneous Coronary Intervention
Adenosine Diphosphate
Blood Platelets
Odds Ratio
Confidence Intervals
Acute Coronary Syndrome
Myocardial Ischemia
Anatomy
Purinergic P2Y Receptor Antagonists
Thrombosis
cangrelor
Stents
Ischemia
Myocardial Infarction
Hemorrhage

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Stone, Gregg W. ; Genereux, Philippe ; Harrington, Robert A. ; White, Harvey D. ; Michael Gibson, C. ; Gabriel Steg, P. ; Hamm, Christian W. ; Mahaffey, Kenneth W. ; Price, Matthew J. ; Prats, Jayne ; Deliargyris, Efthymios N. ; Bhatt, Deepak L. / Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention : Core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial. In: European Heart Journal. 2018 ; Vol. 39, No. 46. pp. 4112-4121.
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title = "Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention: Core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial",
abstract = "Aims In the CHAMPION PHOENIX trial, the potent, rapidly acting, intravenous platelet adenosine diphosphate receptor antagonist cangrelor reduced the 48-h incidence of major adverse cardiac events (MACE; death, myocardial infarction, stent thrombosis, or ischaemia-driven revascularization) compared with a loading dose of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We sought to determine whether the efficacy of cangrelor during PCI varies in patients with simple vs. complex target lesion coronary anatomy. Methods and results Blinded angiographic core laboratory analysis was completed in 10 854 of 10 942 (99.2{\%}) randomized patients in CHAMPION PHOENIX (13 418 target lesions). Outcomes were analysed according to the number of angiographic PCI target lesion high-risk features (HRF) present (bifurcation, left main, thrombus, angulated, tortuous, eccentric, calcified, long, or multi-lesion treatment). The number of patients with 0, 1, 2, and ≥3 HRFs was 1817 (16.7{\%}), 3442 (31.7{\%}), 2901 (26.7{\%}), and 2694 (24.8{\%}), respectively. The 48-h MACE rate in clopidogrel-treated patients increased progressively with lesion complexity (from 3.3{\%} to 4.4{\%} to 6.9{\%} to 8.7{\%}, respectively, P < 0.0001). Cangrelor reduced the 48-h rate of MACE by 21{\%} {4.7{\%} vs. 5.9{\%}, odds ratio (OR) [95{\%} confidence interval (95{\%} CI)] 0.79 (0.67, 0.93), P = 0.006} compared with clopidogrel, an effect which was consistent regardless of PCI lesion complexity (Pinteraction = 0.66) and presentation with stable ischaemic heart disease (SIHD) or an acute coronary syndrome (ACS). By multivariable analysis, the number of high-risk PCI characteristics [OR (95{\%} CI) 1.68 (1.20, 2.36), 2.78 (2.00, 3.87), and 3.23 (2.33, 4.48) for 1, 2, and 3 HRFs compared with 0 HRFs, all P < 0.0001] and treatment with cangrelor vs. clopidogrel [OR (95{\%} CI) 0.78 (0.66, 0.92), P = 0.004] were independent predictors of the primary 48-h MACE endpoint. Major bleeding rates were unrelated to lesion complexity and were not increased by cangrelor. Conclusion Peri-procedural MACE after PCI is strongly dependent on the number of treated high-risk target lesion features. Compared with a loading dose of clopidogrel, cangrelor reduced MACE occurring within 48 h after PCI in patients with SIHD and ACS regardless of baseline lesion complexity. The absolute benefit:risk profile for cangrelor will therefore be greatest during PCI in patients with complex coronary anatomy.",
author = "Stone, {Gregg W.} and Philippe Genereux and Harrington, {Robert A.} and White, {Harvey D.} and {Michael Gibson}, C. and {Gabriel Steg}, P. and Hamm, {Christian W.} and Mahaffey, {Kenneth W.} and Price, {Matthew J.} and Jayne Prats and Deliargyris, {Efthymios N.} and Bhatt, {Deepak L.}",
year = "2018",
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doi = "10.1093/eurheartj/ehy562",
language = "English (US)",
volume = "39",
pages = "4112--4121",
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Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention : Core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial. / Stone, Gregg W.; Genereux, Philippe; Harrington, Robert A.; White, Harvey D.; Michael Gibson, C.; Gabriel Steg, P.; Hamm, Christian W.; Mahaffey, Kenneth W.; Price, Matthew J.; Prats, Jayne; Deliargyris, Efthymios N.; Bhatt, Deepak L.

In: European Heart Journal, Vol. 39, No. 46, 01.01.2018, p. 4112-4121.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention

T2 - Core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial

AU - Stone, Gregg W.

AU - Genereux, Philippe

AU - Harrington, Robert A.

AU - White, Harvey D.

AU - Michael Gibson, C.

AU - Gabriel Steg, P.

AU - Hamm, Christian W.

AU - Mahaffey, Kenneth W.

AU - Price, Matthew J.

AU - Prats, Jayne

AU - Deliargyris, Efthymios N.

AU - Bhatt, Deepak L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Aims In the CHAMPION PHOENIX trial, the potent, rapidly acting, intravenous platelet adenosine diphosphate receptor antagonist cangrelor reduced the 48-h incidence of major adverse cardiac events (MACE; death, myocardial infarction, stent thrombosis, or ischaemia-driven revascularization) compared with a loading dose of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We sought to determine whether the efficacy of cangrelor during PCI varies in patients with simple vs. complex target lesion coronary anatomy. Methods and results Blinded angiographic core laboratory analysis was completed in 10 854 of 10 942 (99.2%) randomized patients in CHAMPION PHOENIX (13 418 target lesions). Outcomes were analysed according to the number of angiographic PCI target lesion high-risk features (HRF) present (bifurcation, left main, thrombus, angulated, tortuous, eccentric, calcified, long, or multi-lesion treatment). The number of patients with 0, 1, 2, and ≥3 HRFs was 1817 (16.7%), 3442 (31.7%), 2901 (26.7%), and 2694 (24.8%), respectively. The 48-h MACE rate in clopidogrel-treated patients increased progressively with lesion complexity (from 3.3% to 4.4% to 6.9% to 8.7%, respectively, P < 0.0001). Cangrelor reduced the 48-h rate of MACE by 21% {4.7% vs. 5.9%, odds ratio (OR) [95% confidence interval (95% CI)] 0.79 (0.67, 0.93), P = 0.006} compared with clopidogrel, an effect which was consistent regardless of PCI lesion complexity (Pinteraction = 0.66) and presentation with stable ischaemic heart disease (SIHD) or an acute coronary syndrome (ACS). By multivariable analysis, the number of high-risk PCI characteristics [OR (95% CI) 1.68 (1.20, 2.36), 2.78 (2.00, 3.87), and 3.23 (2.33, 4.48) for 1, 2, and 3 HRFs compared with 0 HRFs, all P < 0.0001] and treatment with cangrelor vs. clopidogrel [OR (95% CI) 0.78 (0.66, 0.92), P = 0.004] were independent predictors of the primary 48-h MACE endpoint. Major bleeding rates were unrelated to lesion complexity and were not increased by cangrelor. Conclusion Peri-procedural MACE after PCI is strongly dependent on the number of treated high-risk target lesion features. Compared with a loading dose of clopidogrel, cangrelor reduced MACE occurring within 48 h after PCI in patients with SIHD and ACS regardless of baseline lesion complexity. The absolute benefit:risk profile for cangrelor will therefore be greatest during PCI in patients with complex coronary anatomy.

AB - Aims In the CHAMPION PHOENIX trial, the potent, rapidly acting, intravenous platelet adenosine diphosphate receptor antagonist cangrelor reduced the 48-h incidence of major adverse cardiac events (MACE; death, myocardial infarction, stent thrombosis, or ischaemia-driven revascularization) compared with a loading dose of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We sought to determine whether the efficacy of cangrelor during PCI varies in patients with simple vs. complex target lesion coronary anatomy. Methods and results Blinded angiographic core laboratory analysis was completed in 10 854 of 10 942 (99.2%) randomized patients in CHAMPION PHOENIX (13 418 target lesions). Outcomes were analysed according to the number of angiographic PCI target lesion high-risk features (HRF) present (bifurcation, left main, thrombus, angulated, tortuous, eccentric, calcified, long, or multi-lesion treatment). The number of patients with 0, 1, 2, and ≥3 HRFs was 1817 (16.7%), 3442 (31.7%), 2901 (26.7%), and 2694 (24.8%), respectively. The 48-h MACE rate in clopidogrel-treated patients increased progressively with lesion complexity (from 3.3% to 4.4% to 6.9% to 8.7%, respectively, P < 0.0001). Cangrelor reduced the 48-h rate of MACE by 21% {4.7% vs. 5.9%, odds ratio (OR) [95% confidence interval (95% CI)] 0.79 (0.67, 0.93), P = 0.006} compared with clopidogrel, an effect which was consistent regardless of PCI lesion complexity (Pinteraction = 0.66) and presentation with stable ischaemic heart disease (SIHD) or an acute coronary syndrome (ACS). By multivariable analysis, the number of high-risk PCI characteristics [OR (95% CI) 1.68 (1.20, 2.36), 2.78 (2.00, 3.87), and 3.23 (2.33, 4.48) for 1, 2, and 3 HRFs compared with 0 HRFs, all P < 0.0001] and treatment with cangrelor vs. clopidogrel [OR (95% CI) 0.78 (0.66, 0.92), P = 0.004] were independent predictors of the primary 48-h MACE endpoint. Major bleeding rates were unrelated to lesion complexity and were not increased by cangrelor. Conclusion Peri-procedural MACE after PCI is strongly dependent on the number of treated high-risk target lesion features. Compared with a loading dose of clopidogrel, cangrelor reduced MACE occurring within 48 h after PCI in patients with SIHD and ACS regardless of baseline lesion complexity. The absolute benefit:risk profile for cangrelor will therefore be greatest during PCI in patients with complex coronary anatomy.

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