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

AimsIn 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 resultsBlinded 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.ConclusionPeri-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

The efficacy and safety of cangrelor in single vessel vs multivessel percutaneous coronary intervention: Insights from CHAMPION PHOENIX

“…This may inform the selection of a particular antiplatelet medication strategy at the start of a case, which is often before final decisions about degree of revascularization are necessarily made. Additionally, in combination with recent findings of the benefit of cangrelor in the treatment of lesions with high risk features, these results suggest an expanded repertoire of clinical scenarios in which cangrelor may be the antiplatelet agent of choice.…”

Optimal Antithrombotic Treatment of Patients with Atrial Fibrillation Early after an Acute Coronary Syndrome—Triple Therapy, Dual Antithrombotic Therapy with an Anticoagulant… Or, Rather, Temporary Dual Antiplatelet Therapy?

“…The calculated equipoise between NNTBs for stroke versus coronary events is at CHA 2 DS 2 VASc = 4 for DAPT with ticagrelor instead of DAT and at CHA 2 DS 2 VASc = 5 for DAPT with prasugrel instead of DAT ( Figure 4 ). In patients with high-risk target lesions [ 16 , 25 , 26 ], the rate of early cardiovascular events, including stent thrombosis, is further increased and, accordingly, the above mentioned NNTBs deriving from the use of the new P2Y 12 inhibitors instead of clopidogrel (the recommended P2Y 12 inhibitor in case of TAT) are expected to be even lower. A 3.4 HR for early stent thrombosis is expected to occur in clopidogrel-treated ACS patients with ≥ 3 compared to one high-risk procedural feature among the following: long, bifurcated, eccentric, thrombotic, tortuous, angulated or calcified lesions, left main and multiple vessel PCI [ 16 ].…”

Commentary: Temporarily omitting oral anticoagulants early after stenting for acute coronary syndromes patients with atrial fibrillation

“…1 and 2). In patients with high-risk target lesions (long, bifurcated, eccentric, thrombotic, tortuous, angulated or calcified lesions, left main and multiple vessel PCI) [16], the rate of early cardiovascular events, including stent thrombosis, further increases. As a consequence, a sharp further reduction in the above mentioned NNTBs can be expected with the use of the newer agents in case of high-complexity PCIs.…”