No Interplay Between Access Site, Cangrelor Effects in PCI Patients

Cangrelor reduces ischemic events and does not increase severe bleeding compared with clopidogrel, regardless of PCI access site, according to a prespecified subanalysis of CHAMPION PHOENIX published online September 23, 2015, ahead of print in the European Heart Journal. With use of either drug, bleeding complications were lower with radial vs femoral access.

Take Home:  No Interplay Between Access Site, Cangrelor Effects in PCI Patients

“The combination of cangrelor and radial access appears to be a particularly appealing strategy to minimize both ischemic and bleeding events,” said study investigator Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), in an email interview with TCTMD.

For the double-blind, double-dummy CHAMPION PHOENIX trial, researchers led by Dr. Bhatt randomized 11,145 patients who were undergoing either urgent or elective PCI to receive either cangrelor (Kengreal; The Medicines Company) or clopidogrel. In all, 10,942 patients comprised the modified intention-to-treat (mITT) population, by virtue of having received the study treatment and undergone PCI. Compared with clopidogrel, cangrelor reduced the rate of the primary efficacy endpoint of all-cause death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours without increasing the primary safety endpoint of GUSTO-defined severe bleeding.

In the current analysis, Dr. Bhatt and colleagues looked at the potential effects of access site on outcome within the mITT population. Access route was determined by site investigators, with 74% of patients receiving femoral PCI and 26% radial PCI.

Ischemic Events Lower, Bleeding Risk Similar

In the femoral group, cangrelor-treated patients had higher prevalence of PAD and a lower rate of glycoprotein IIb/IIIa inhibitor use than did clopidogrel-treated patients. In the radial group, cangrelor-treated patients had lower median weight.

Compared with the femoral cohort, patients who had radial access were more likely to have diabetes and a history of PCI but less likely to be current smokers or to have prior MI or CABG. At the time of PCI, patients in the radial group were less likely to receive aspirin, low-molecular-weight heparin, or the clopidogrel loading dose of 600 mg (vs 300 mg) and more apt to receive unfractionated heparin. Radially treated patients were more likely to be implanted with DES than were femorally treated patients.

At 48 hours, patients had a lower risk of the primary endpoint with cangrelor compared with clopidogrel regardless of whether PCI was performed via radial or femoral access, although in the radial group that benefit only reached a trend. Neither group had greater odds of GUSTO severe bleeding when receiving cangrelor (table 1).

Table 1. Outcomes at 48 Hours by Antiplatelet Drug, Access Site

When using the more sensitive definition of ACUITY major bleeding, risk was elevated with cangrelor vs clopidogrel in both the femoral (OR 1.69; 95% CI 1.35-2.12) and radial groups (OR 2.17; 95% CI 1.02-4.62), again with no interplay between treatment effect and access site (P for interaction = .54). Blood transfusion also was similarly likely for cangrelor and clopidogrel when using either access route (P for interaction = .99).

Between femoral and radial PCI, there was no disparity in the primary endpoint. GUSTO severe/moderate bleeding was 0.5% in the femoral group and 0.2% in the radial group (P = .05). On multivariable analysis, bleeding risk remained similar between the 2 groups when defined as GUSTO severe/moderate and TIMI major/minor. However, ACUITY major/minor bleeding was reduced with radial vs femoral access (adjusted OR 0.70; 95% CI 0.59-0.83).

Additionally, there were some signs of a differential in stent thrombosis between the femoral and radial cohorts, with the latter showing increased risk among patients on clopidogrel (1.5%) compared with cangrelor (0.8%; P for interaction = .09). “The lack of benefit regarding stent thrombosis in the radial cohort is conceivably due to a low event frequency,” the researchers suggest.

Support for Radial Access

“This study shows that in a large, diverse, international PCI population, radial access is associated with less bleeding than a femoral approach,” Dr. Bhatt commented. “Thus, it isn’t just randomized trials of radial versus femoral access with highly experienced radial operators where the good results with radial access are seen.”

The analysis also demonstrates “that the benefits of intravenous cangrelor over in-cath lab clopidogrel loading are present regardless of vascular access route, without any excess in transfusion risk even in femoral PCI,” he noted.

In the paper, the researchers point out that the edge held by cangrelor may “be attenuated in the setting of more prolonged pretreatment with clopidogrel or with the use of ticagrelor or prasugrel.”

Yet Sorin J. Brener, MD, of New York Methodist Hospital (New York, NY), stressed to TCTMD in a telephone interview that there was no randomization to access site. “The patients are obviously selected for a reason, either because of the skill of the operator or another reason,” he said, noting that, as such, the study is more “descriptive” than prescriptive.

“What it does show very nicely, though, is the fact that a lot of the bleeding has nothing to do with the access site and so if one therapy is better than the other, than the risk reduction would be similar—and that’s exactly what we see in this paper,” Dr. Brener commented. The main take home, he added, is the lack of interaction.

Interestingly, despite the seeming “desire to present radial as the preferred approach, 75% of patients in this trial were treated via the femoral route,” Dr. Brener said. “So apparently, still people prefer [femoral].”

Note: Study coauthors Gregg W. Stone, MD, and Philippe Généreux, MD, are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Gutierrez JA, Harrington RA, Blankenship JC, et al. The effect of cangrelor and access site on ischaemic and bleeding events: insights from CHAMPION PHOENIX. Eur Heart J. 2015;Epub ahead of print.

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  • Dr. Bhatt reports relationships with multiple pharmaceutical and device companies.
  • Dr. Brener reports no relevant conflicts of interest.

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