LONDON – Ticagrelor was associated with fewer major bleeding complications compared with clopidogrel when stopped before revascularization surgery, in a large observational study that included all patients on dual antiplatelet therapy who underwent bypass surgery over a 2-year period in Sweden.
The overall incidence of major bleeding was 12.9% and 17.6%, respectively, when these antiplatelet agents were stopped before coronary artery bypass grafting (CABG). The adjusted odds ratio (OR) was 0.72, representing a 28% lower incidence with ticagrelor than with clopidogrel (P = .012).The study findings indicated that it might be safe to stop ticagrelor but not clopidogrel slightly closer to the procedure than is currently recommended by European (Eur Heart J. 2014;35:2541-2619) and American (J Am Coll Cardiol. 2013;61:e179-e347) guidelines.
“The overall incidence of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel,” Dr. Anders Jeppsson said at the annual meeting of the European Society of Cardiology.
“The difference was mainly driven by a lower incidence when clopidogrel and ticagrelor were discontinued 72 to 120 hours before surgery,” he added.
Dr. Jeppsson of Sahlgrenska (Sweden) University Hospital and the University of Gothenburg noted that the incidence of CABG-related major bleeding was highest for both antiplatelet agents when they were stopped less than 24 hours before surgery but that there was no significant difference between the two antiplatelet agents.
“Discontinuation of ticagrelor 3 days before CABG, as opposed to 5 days, did not increase the incidence of major bleeding complications,” he reported. The OR for discontinuing ticagrelor at 72-120 hours versus more than 120 hours before surgery was 0.93 (P = .08). However, the situation was not the same for discontinuing clopidogrel, with a higher rate of bleeding when the drug was discontinued closer to surgery (OR = 1.17, P = .033).
The findings, which were published online Sept. 1 in the European Heart Journal (doi:10.1093/eurheartj/ehv381), come from an analysis of data prospectively obtained from the SWEDEHEART registry and other local Swedish registries, databases, and patient records. Dr. Jeppsson explained that the aims were to compare the incidence of CABG-related bleeding complications among patients with acute coronary syndromes (ACS) who were taking dual antiplatelet therapy with aspirin and either clopidogrel or ticagrelor in a real-world setting and to see if shorter discontinuation periods before surgery might be feasible.
“A short discontinuation time would reduce the risk for thrombotic events while waiting [for surgery] and save hospital resources,” Dr. Jeppsson said. “But on the other hand it may increase the risk for bleeding complications.”
Data from January 2012 to December 2013 were obtained on all patients in Sweden who were taking dual antiplatelet therapy before CABG. This time period was chosen as it was when ticagrelor was first introduced for the first-line treatment of ACS in the country. Of 2,418 patients identified, 10 were taking prasugrel and were excluded from the analysis. A further 164 patients were excluded as they had discontinued dual antiplatelet therapy more than 2 weeks before having surgery, leaving 1,266 patients who had received ticagrelor and 978 who had been taking clopidogrel.The Bleeding Academic Research Consortium (BARC) Type 4 definition (Circulation. 2011;123:2736-47) was primarily used to identify CABG-related bleeding, with three other published definitions also used, including those used in the BART (N Engl J Med. 2008;358:2319-31) and PLATO (N Engl J Med. 2009;361:1045-57) antiplatelet trials.The overall incidence of major bleeding complications was significantly lower with ticagrelor versus clopidogrel using all four of the bleeding definitions.
However, discontinuing ticagrelor 24 hours or less before CABG showed that while there was a similar amount of BARC major bleeding (P = .052) compared with stopping clopidogrel, the median amount of blood loss (P less than .001), need for red blood cell (P = .028) or platelet (P less than .001) transfusion was greater.To illustrate the dangers of major bleeding on patient outcome, Dr. Jeppsson noted that patients who experienced major bleeding were almost 15 times more likely to die 30 days after the procedure than were those who had no major bleeding. The 30-day mortality rate was higher in clopidogrel than ticagrelor-treated patients (2.7% vs 1.7%) and incidence of thrombotic events was 2.8% and 2.3% These are unadjusted findings and the study was not statistically powered to look at these as end points, Dr. Jeppsson emphasized. These factors were registered for safety reasons, he said.
The study was supported by an investigator-sponsored study program of AstraZeneca and the Swedish Heart and Lung Foundation. Dr. Jeppsson has received research grants, consulting fees or speaker’s honorarium from AstraZeneca in addition to several other pharmaceutical companies.