Cangrelor Bridging Leans Heavy-Handed in the Real World

There was little room for error but plenty of confusion regarding the dosing of cangrelor (Kengreal) for perioperative antiplatelet bridging, according to a retrospective chart review.

Among 222 patients who got their index percutaneous coronary intervention (PCI) and finished their oral antiplatelet therapy before getting a first IV infusion of cangrelor and subsequent surgery within 6 months, there was a reduced risk of a major adverse cardiovascular event (MACE) when bridging cangrelor was administered at 0.75 mcg/kg/min (6%) versus a lower dose (19.2%), reported Aakash Garg, MD, of Ellis Hospital in Schenectady, New York.

Meanwhile, moderate bleeding was more common following cangrelor bridging infusions >0.75 mcg/kg/min (4.4% vs 0% with lower doses), Garg reported at the Society for Cardiovascular Angiography and Interventions (SCAI) annual meeting held in Montreal.

The apparent sweet spot for cangrelor bridging, 0.75 mcg/kg/min, had been administered to just 22.5% of patients. It turned out that cangrelor was more commonly given at the PCI infusion rate (4 mcg/kg/min; 48.6% of cases) given the lack of guidance for bridging purposes.

“Real-world data demonstrate substantial variability in cangrelor dosing among patients receiving antiplatelet therapy as a bridging strategy prior to surgery. There is a suggestion that dosing patterns may affect outcomes,” Garg said in a press release. “These findings highlight the need for further research and continued evaluation of dosing patterns and clinical outcomes to improve decision-making in patients requiring bridging intravenous antiplatelet therapy following PCI.”

The present study confirms that there’s a lot of confusion surrounding the optimal dosing of cangrelor in patients requiring surgery after PCI, said Dominick Angiolillo, MD, PhD, of the University of Florida in Jacksonville, who was not involved in the study.

Angiolillo emphasized the need for more education on the topic and said these findings should encourage an update to cangrelor’s package insert.

Cangrelor was FDA approved in 2015 as an adjunct to PCI in patients not treated with another P2Y12 platelet inhibitor or a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor. The official recommended dose is a 30 mcg/kg IV bolus, followed immediately by a 4 mcg/kg/min IV infusion for the duration of PCI or at least 2 hours, whichever is longer.

Notably absent from the label is mention of cangrelor for perioperative bridging or a recommended dose for this indication.

“A challenge for physicians is that unlike the PCI dose of cangrelor, which is FDA approved based on CHAMPION PHOENIX, the bridging dose of cangrelor is not FDA approved. So there is less guidance for physicians, and unstudied dosing is more common in the setting of bridging,” commented Deepak Bhatt, MD, MPH, of Mount Sinai Fuster Heart Hospital in New York City.

The balance of ischemic and hemorrhagic complications is particularly important in the setting of early surgery after coronary stent implantation. While GPIIb/IIIa inhibitors are an option, the IV reversible P2Y12 platelet inhibitor cangrelor is the only IV agent that has a bridging-specific dose shown to be effective and safe in a randomized controlled trial.

In 2012, the BRIDGE trial report from Angiolillo’s group showed the pharmacodynamic feasibility of IV cangrelor at 0.75 mcg/kg/min for perioperative maintenance of platelet inhibition in patients awaiting coronary artery bypass grafting (CABG) surgery, with no significant uptick in bleeding.

These results are already over a decade old, Angiolillo stressed in an interview. “With a dedicated trial, a dedicated dose, why can’t there just be an insert on the label?”

Granted, a minority of BRIDGE participants had actually undergone PCI before CABG, and the type of stent and timing of PCI were unclear.

The bigger question is who exactly needs to be bridged in the first place, Bhatt told MedPage Today. “Well-powered randomized trials are required to address all these knowledge gaps.”

Garg and colleagues conducted their multicenter retrospective cohort study from January 2020 to November 2025 for the present report.

Included were 222 patients who had cangrelor bridging between PCI and subsequent surgery (78.4% men, 68% white, mean age 64.6 years).

PCI and surgery occurred within the same hospitalization in 37.4% of cases (32% different hospitalization, 30.6% unknown), according to study authors, with a median time of 24 days from PCI to subsequent surgery. These subsequent surgeries were more commonly urgent (70.3%) and cardiac procedures (58.1%). Noncardiac surgeries represented included gastrointestinal/abdominal surgery and orthopedic surgery.

Following PCI, most patients were put on aspirin (76.6%), with clopidogrel (39.6%) and ticagrelor (31.5%) also commonly prescribed as antiplatelets.

MACE occurred in 8.1% of cases within 72 hours after surgery, while the incidence of any bleeding after surgery was 3.6%; for moderate bleeding, the figure reached 2.7%.

Cangrelor dose aside, other factors associated with perioperative MACE were cardiac surgery as opposed to noncardiac surgery (11.6% vs 3.2%) and surgery during the same admission as the PCI (13.3% vs 0% with a different admission), according to Garg.

He also reported that moderate bleeding was more common with cardiac surgery (4.7% vs 0% with noncardiac surgery).

Bhatt noted the non-randomized design as a limitation of the study. However, he said the results “make biological and intuitive sense” as they are “in keeping with a large body of literature showing that underdosing or overdosing of anti-thrombotic medications is associated with increased adverse events.”