Impact of Cerebrovascular Events Older Than One Year on Ischemic and Bleeding Outcomes With Cangrelor in Percutaneous Coronary Intervention

Abstract

Background-Cangrelor is a potent intravenous adenosine diphosphate-receptor antagonist that in the CHAMPION trials reduced the 48-hour and 30-day rates of ischemic events during percutaneous coronary intervention without an increase in severe bleeding. Coronary Intervention) were 3 randomized, double-blind, double-dummy trials in which cangrelor was compared with clopidogrel during percutaneous coronary intervention. The effect of cangrelor on ischemic events and bleeding was analyzed in the subgroup of patients with a history of cerebrovascular events at least 1 year prior to randomization; the Breslow-Day test was used to test for interaction of treatment effect in subgroups with and without such a history. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours. Among 24 910 randomized patients, 1270 patients (5.1%) had a cerebrovascular event >1 year old, including 650 assigned to cangrelor and 620 assigned to clopidogrel. Consistent with the overall trial results, the rate of the primary efficacy end point was 4.3% in the cangrelor group versus 5.3% in the clopidogrel group (odds ratio 0.80; 95% confidence interval 0.48-1.34; P=0.40; P for interaction =0.97), and the rate of GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding was 0.3% in both groups (P=0.97; P for interaction =0.81). Conclusions-Among patients in the CHAMPION trials with a prior cerebrovascular event at least 1 year before the percutaneous coronary intervention, the efficacy and bleeding profile of cangrelor compared with clopidogrel was similar to that in the overall trial. (Circ Cardiovasc Interv. 2017;10:e004380. Methods and Results-CHAMPION

Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelor) in percutaneous coronary intervention: from pharmacology to indications for clinical use

“…68 In two analyses of patients with a history of cerebrovascular events or MI the efficacy and safety profile of cangrelor compared with clopidogrel were consistent with the overall population. 69,70 In another study, cangrelor was not associated with acquired thrombocytopenia, a cause of early morbidity and major bleeding, whose main predictor was the use of GPIs. 71 Finally, in the three CHAMPION trials combined, the use of GPIs was not shown to reduce ischemic complications, and rather caused an increase in bleeding rates in the cangrelor and clopidogrel or placebo groups.…”

Novel Antiplatelet Therapies for Atherothrombotic Diseases

“…40 Additional evidence suggests that the benefits of cangrelor are maintained across several high-risk subgroups, including those with a history of stroke ≥1 year from the time of PCI, older patients, and in those on a background of anticoagulant therapy with heparin, without concomitant increases in the rates of major bleeding. 41–44…”

Cangrelor in Percutaneous Coronary Intervention: Current Status and Perspectives

“…Similarly, GUSTO severe bleeding rate was not differentiated by prior history of ischemic stroke or transient ischemic attack, P for interaction = .81. 20 Finally, in a very recent pooled, patient-level analysis of the 3 CHAMPION trials, cangrelor maintained its efficacy in reducing ischemic complications: among patients receiving GPI, the primary end point rate was 4.9% versus 6.5% in cangrelor versus clopidogrel arms, respectively, with OR (95% CI) of 0.74 (0.55-1.01), while in patients who did not receive GPI, 3.6% versus 4.4% in cangrelor versus clopidogrel arms, with OR (95% CI) 0.82 (0.72-0.94) and P for interaction = .55. Severe/life-threatening bleeding as defined by GUSTO did not differ according to the GPI use.…”