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.

Clinicaltrials.gov identifier: NCT01156571.

Figures

Figure 1

Histogram of the number of high-risk target lesion features treated per patient. The mean number of high-risk features per patient was 1.8 ± 1.4 [median (25th percentile, 75th percentile) = 2 (1, 2); range 0–11 per patient]. Note: Each treated lesion has no more than nine high-risk features. For patients with more than one treated lesion, the total number of high-risk features is summed for each lesion. Thus, an individual patient with multiple treated lesions may have >9 high-risk features. HRF, high-risk feature.

Figure 2

Presence (proportion) of qualifying high-risk features in 10 854 patients and in 13 418 lesions. Note: Each lesion has no more than nine high-risk features. For patients with more than one treated lesion, the total number of high-risk features is summed for each lesion. Thus, an individual patient with multiple treated lesions may have >9 high-risk features. Analysis by quantitative and qualitative coronary angiography performed at an independent blinded core laboratory. NA, not applicable.

Figure 3

Major adverse cardiovascular event rates at 48 h according to the number of high risk features. The 95% confidence intervals for each rate estimate appear in parentheses. HRF, high-risk features; MACE, major adverse cardiovascular events.

Figure 4

Major adverse cardiovascular events at 48 h following randomization to cangrelor vs. clopidogrel according to the number of treated high-risk target lesion features. (A) All patients. The P-value for the trend relating the number of treated high-risk lesion features to the 48-h rate of major adverse cardiovascular events was <0.0001 for both the clopidogrel-treated and cangrelor-treated groups, and the reduction with cangrelor was consistent regardless of target lesion complexity. (B) Further stratified by clinical syndrome acuity at the time of presentation. The reduction in peri-procedural adverse events with cangrelor compared with clopidogrel was consistent regardless of target lesion complexity and clinical presentation. Limit lines for each rate estimate represent 95% confidence intervals. ACS, acute coronary syndrome; HRF, high-risk features; MACE, major adverse cardiovascular events; SIHD, stable ischaemic heart disease.

Figure 5

Myocardial infarction and stent thrombosis at 48 h following randomization to cangrelor vs. clopidogrel according to the number of treated high-risk target lesion features. (A) Myocardial infarction, all patients; (B) Myocardial infarction, further stratified by clinical syndrome acuity at the time of presentation. (C) Stent thrombosis, all patients; (D) stent thrombosis, further stratified by clinical syndrome acuity at the time of presentation. Limit lines for each rate estimate represent 95% confidence intervals. ACS, acute coronary syndrome; HRF, high-risk features; MACE, major adverse cardiovascular events; SIHD, stable ischaemic heart disease.