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Cangrelor reduces ischemia complications, with or without glycoprotein IIb/IIIa inhibitors
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Reductions in ischemia complications achieved with cangrelor in patients undergoing PCI are maintained regardless of whether glycoprotein IIb/IIIa inhibitors were administered, according to recent findings.
In the pooled, patient-level analysis of the three CHAMPION trials, researchers assessed 24,902 patients who underwent PCI and were treated with cangrelor (Kengreal, Chiesi USA).
The CHAMPION trials were prospective, double blind, double dummy randomized trials in which patients aged at least 18 years with an indication for elective or nonelective PCI were randomly allocated to a treatment regimen of cangrelor (30 µg/kg bolus, followed by 4 µg/kg/min infusion for ≥ 2 hours or the length of PCI, whichever was longer) or clopidogrel.
Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor treatment was permitted only as a bailout/rescue strategy, except in the CHAMPION PCI trial, in which GPIIb/IIIa inhibitors could be used in a routine or bailout/rescue capacity at the discretion of the site investigator. The primary efficacy endpoint was a composite of all-cause mortality, MI, ischemia-driven revascularization or stent thrombosis at 48 hours after randomization. The secondary efficacy endpoint was stent thrombosis at 48 hours.
Safety was evaluated using the GUSTO, TIMI and ACUITY bleeding scales, and the primary overall safety endpoint in the CHAMPION trials was GUSTO-defined non-CABG severe or life-threatening bleeding.
Benefit of cangrelor
The researchers found that GPIIb/IIIa inhibitors were used in 3,173 patients (12.7%). The most commonly used GPIIb/IIIa inhibitor was eptifibatide (69.4%), followed by abciximab (19.4%; ReoPro, Centocor) and tirofiban (10.8%; Aggrastat, Medicure).
No heterogeneity was found across the three trials in terms of cangrelor’s effect on the primary efficacy endpoint in all CHAMPION modified intention-to-treat patients, patients receiving GPIIb/IIIa inhibitors and patients who did not receive GPIIb/IIIa inhibitors.
Although there was variation in the indications for PCIs, there were not significant differences in the baseline characteristics of patients in the cangrelor and clopidogrel arms in subsets receiving or not receiving GPIIb/IIIa inhibitors. Patients receiving cangrelor had lower rates of the primary composite endpoint vs. those receiving clopidogrel, both in patients who received GPIIb/IIIa inhibitors (4.9% vs. 6.5%; OR = 0.74; 95% CI, 0.55-1.01) and those who did not receive a GPIIb/IIIa inhibitor (3.6% vs. 4.4%; OR = 0.82; 95% CI, 0.72-0.94; P for interaction = .55).
Cangrelor was not associated with an increase in the primary safety endpoint of GUSTO-defined severe/life-threatening bleeding, either in patients who received GPIIb/IIIa inhibitors (0.4% vs. 0.5%; OR = 0.71; 95% CI, 0.25-1.99) or those who did not receive GPIIb/IIIa inhibitors (0.2% vs. 0.1%; OR = 1.56; 95% CI, 0.8-3.04). The use of GPIIb/IIIa inhibitors was linked to increased bleeding risk in both groups, the researchers wrote.
Thresholds questioned
In a related editorial, Somjot S. Brar, MD, MPH, of the Kaiser Permanente Medical Center, Los Angeles, noted that a better understanding is needed of the prognostic powers of the study’s endpoints, particularly periprocedural MI.
“Although limiting MI during PCI is likely of benefit, the threshold for a worsening prognosis associated with increasing cardiac biomarkers without procedural complications is ill-defined,” Brar wrote. “Recent analyses from multiple [ACS] trials show no association of periprocedural MI with long-term mortality, and a position paper suggests a higher threshold of biomarker elevation be considered than was used in the present analysis.” – by Jennifer Byrne
Disclosure: The Medicines Company supported the CHAMPION program. Please see the full study for a list of the researchers’ relevant financial disclosures. Brar reports no relevant financial disclosures.
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