Ticagrelor Safe If Stopped at Least One Day Before CABG

By Marilynn Larkin

NEW YORK - Pretreating coronary artery bypass grafting (CABG) patients with ticagrelor is safe, if the antithrombotic is discontinued more than 24 hours before surgery, researchers suggest.

"Patients requiring CABG represent a challenging group of individuals because of the difficulties in balancing thrombosis and bleeding risks in relation to the timing of surgery and optimal antithrombotic therapy management," write Dr. Riccardo Gherli of San Camillo Forlanini Hospital in Rome, Italy and colleagues.

"Current revascularization guidelines and the US Food and Drug Administration-approved patient labeling recommend discontinuation of ticagrelor therapy 5 days before surgery," they note. "Concern exists that a discontinuation of several days may be associated with an increased risk of cardiovascular events while awaiting surgery."

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To investigate, the team compared the safety of preoperative ticagrelor - a platelet aggregation inhibitor produced by AstraZeneca and marketed as Brilinta in the US and Brilique in Europe - with or without aspirin versus aspirin alone in patients with acute coronary syndromes (ACS) undergoing CABG.

As reported in JAMA Cardiology, online September 21, the research team analyzed data from the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry on 786 patients. Preoperative antiplatelet regimens included aspirin alone in 496 patients and ticagrelor with or without aspirin in 290 patients. (In the ticagrelor group, all but 20 patients received dual antiplatelet therapy with aspirin.)

Because of baseline differences in the study groups, the authors used a propensity score distribution to identify 215 matched pairs of patients.

Analyses of the matched pairs revealed that preoperative use of ticagrelor was associated with a similar risk of bleeding according to the Universal Definition of Perioperative Bleeding (UDPB) and E-CABG bleeding criteria; however, the incidence of platelet transfusion was higher in the ticagrelor group (13.5%, versus 6.0% in patients taking aspirin alone).

Continuing ticagrelor up to the time of surgery or discontinuing it less than two days before surgery was associated with a higher risk of platelet transfusion (22.7% of patients versus 6.4% of those receiving aspirin alone) and E-CABG bleeding grades 2 and 3 (18.2% versus 5.9%). Those taking ticagrelor also tended to have an increased risk of UDPB bleeding grades 3 and 4 (22.7% versus 9.6%).

Among those in whom the drug was discontinued at least two days before surgery, the incidence of platelet transfusion was 12.4% in the ticagrelor group and 3.6% in the aspirin-alone group.

The team concluded that use of preoperative ticagrelor with or without aspirin compared with aspirin alone was associated with more platelet transfusion, but a similar degree of bleeding. By contrast, in patients receiving ticagrelor one day before or up until surgery, there was an increased rate of severe bleeding.

Interventional cardiologist Dr. Robert Kumar of the Sharp Rees-Stealy Medical Group in San Diego, California, told Reuters Health, "Antiplatelet therapy with aspirin and a P2Y12 inhibitor such as clopidogrel or ticagrelor has been shown to significantly reduce ischemic endpoints in patients with ACS. We know that in these patients time is of the essence, and earlier restoration of blood flow is associated with a greater amount of myocardial salvage."

"On the other hand, several studies have suggested that P2Y12 inhibitor use prior to CABG increases bleeding, and we know that up to 10% of patients with ACS undergoing revascularization receive CABG instead of PCI," he said by email.

"The challenge comes when we try to maximize the benefits of early anticoagulant and antiplatelet therapies without causing major bleeding . . . The American College of Cardiology recommends discontinuing ticagrelor for five days prior to CABG. However, waiting five days for surgery with unstable patients can be difficult for both patients and providers, and may increase patient risk and hospital costs," he observed.

He added, "The current study adds further clarity to the debate of how long we need to wait for CABG in ACS patients who have been pretreated with ticagrelor prior to angiography, when the coronary anatomy is unknown and the revascularization strategy remains to be decided."

Dr. Kumar concluded, "While this analysis is limited by a small number of patients in the propensity matched groups, the data may be reassuring to physicians who feel that waiting five days for surgery after stopping ticagrelor is not a safe option clinically, and waiting two or three days may be a more reasonable strategy."

Dr. Gregg Fonarow, director of the Ahmanson-UCLA Cardiomyopathy Center and co-chief of the UCLA Division of Cardiology, also commented by email. "These findings suggest there may be select patients where if the patient has received ticagrelor it may not be necessary to wait five to seven days before proceeding with surgery," he told Reuters Health. "However, as these data are observational, and potentially subject to confounding, further studies are needed."

The authors did not respond to requests for a comment.

SOURCE: https://bit.ly/2dtlZvL

JAMA Cardiol 2016.

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