An early surgical bypass strategy just 2 to 3 days after stopping ticagrelor is noninferior in terms of safety and clinical outcomes compared to delaying surgery 5 to 7 days as current North American guidelines recommend, new trial data suggest. Findings from the study, which is the first randomized trial evaluating the safety of early coronary artery bypass graft (CABG) surgery after a shorter cessation of ticagrelor, were reported Saturday at the American Heart Association (AHA) Scientific Sessions 2021 virtual meeting. “We discovered no significant increase in bleeding when people had bypass surgery after 2-3 days of discontinuing ticagrelor,” said lead study author Derek So, MD, a cardiologist at the University of Ottawa Heart Institute and a professor at the University of Ottawa. “These findings may be surprising based on the assumption that the presence of a strong blood thinner should predispose people to severe bleeding,” he said. So noted that the results of the trial could have important implications for future clinical recommendations – especially in the US and Canada. "We think that the results of our study might have implications on future North American guidelines by decreasing the time to surgery and increasing the level of evidence for European and Asian guidelines." Bleed concerns Ticagrelor is the standard-of-care platelet P2Y12 receptor inhibitor for acute coronary syndrome (ACS) patients. Over 10% of patients with ACS require CABG after being prescribed ticagrelor; however, due to its potency and concerns about perioperative bleeding, American College of Cardiology/AHA guidelines advocate interruption of ticagrelor for 5 days before CABG if surgery is non-emergent (Level B evidence). "In contrast, in Europe, the suggestion is at least waiting 3 days," explained So, noting that all recommendations are currently based on retrospective evidence. While multiple studies have suggested earlier surgery after just 2 days of ticagrelor cessation is safe, he said added that “until now,” there has been a lack of randomized trial data to determine safety or clinical outcomes of this strategy compared to the guideline standard of 5 to 7 days after ticagrelor cessation. The RAPID CABG (Reassessment of Anti-Platelet Therapy Using InDividualized Strategies – Ticagrelor in Patients With Acute Coronary Syndromes Treated by Coronary Artery Bypass Graft Surgery) trial was set up to evaluate the safety and clinical outcomes of shortening the waiting time between stopping ticagrelor and surgery, he said. Trial details The RAPID CABG trial randomized assigned 143 patients requiring CABG and currently taking ticagrelor into two groups at two centers in Canada – with 72 patients randomized to earlier surgery after just 2 or 3 days, while 71 patients had surgery after the standard 5- to 7-day wait. The primary outcome of the trial was severe or massive bleeding, as defined by the Universal Definition of Perioperative Bleeding (UDPB): class 3 or 4, said So, noting that this endpoint was chosen due to its known relationship to mortality. He noted that while bloodwork showed higher residual antiplatelet effects in the early group versus the delayed group, there was no statistical difference in the primary endpoints, noting that 4.6% of the early CABG group had class 3 or 4 bleeding compared to 5.2% in the delayed group (P=0.025 for noninferiority). So also noted that the trial assessed several secondary bleeding outcomes, including Thrombolysis in Myocardial Infection (TIMI) CABG bleeds and Bleeding Academic Research Consortium (BARC) types 4 or 5 bleeding – which are bypass related bleeding and fatal bleeding respectively. “None of these had any differences between groups,” said So, adding that that six patients (9%) in the delayed surgery group experienced recurrent angina, recurrent heart attack and ventricular arrhythmias that prompted earlier surgery. In contrast, no one in the early surgery group had to have surgery earlier than 2 days after they stopped taking ticagrelor, he said. Furthermore, the early surgery group had a reduced length of hospital stay by 3 days (9 days vs 12 days from randomization to discharge), he revealed. “Research such as this, with people randomly allocated to early vs. delayed surgery, is integral to assure cardiologists and surgeons that early surgery is safe, especially since it conflicts with the present guidelines for people who are taking ticagrelor,” said So. “Furthermore, although our study was not large enough to evaluate whether early surgery protects people from suffering early recurrent heart attacks or angina, it opens this hypothesis and may prompt future research in the area,” he added.