Earlier CABG after Ticagrelor administration found to be safe: RAPID CABG Trial

Key Points

• Current US Guidelines recommend a 5- day waiting period for non-urgent CABG after cessation of ticagrelor to prevent high bleeding rates; European guidelines recommend 3 days.
• In the PLATO trial, a higher proportion of patients who died from CABG had received Ticagrelor within 1 day of surgery.
• RAPID CABG randomized participants undergoing non-urgent CABG to an early surgery (2-3 days after ticagrelor administration) versus a delayed surgery (5 days or more after ticagrelor administration).
• Patients who underwent early surgery were found to have no difference in Class 3 or 4 bleeding when compared to those undergoing delayed surgery. Participants in the early CABG arm also had lower lengths of stay.

The optimal timing of coronary artery bypass grafting (CABG) after administration of P2Y-12 inhibitors has not been established.  The PLATO trial, in which participants were randomized to receive either clopidogrel or ticagrelor for acute coronary syndrome, a total of 1,266 participants underwent CABG as their revascularization strategy. While Ticagrelor was found to have a decrease in CV mortality, death was associated with earlier CABG, with the highest in those undergoing surgery within 1 day or less from their event. The observational data from this study informed decisions to delay CABG for nonurgent cases after cessation of P2Y-12 inhibitors, especially ticagrelor. The current AHA/ACC guidelines recommend waiting 5 days after cessation of ticagrelor to undergo CABG, whereas European guidelines have truncated the time to 3 days. Regardless, a head-to-head comparison of the early versus delayed CABG strategy had never been done.

Today, in a Late-Breaking session at the 2021 American Heart Association Scientific Sessions, Dr. Derek So of the University of Ottawa Heart Institute in Canada presented data from the RAPID CABG trial, which sought to answer this very question. This physician-initiated randomized control trial randomized participants who received ticagrelor and were subsequently referred for CABG to enter an early CABG arm, where they would undergo surgery in 2-3 days, or a delayed CABG arm, in which they would undergo surgery in 5-7 days. The hypothesis was that an early CABG strategy would be noninferior to delayed CABG with respect to bleeding outcomes. For the modified intention to treat analysis, 71 patients were randomized to the early group, and 69 to the delayed (6 patients crossed over from early to late, and 7 from late to early based on medical necessity).

Participants were mostly male with average age of 63 years. There was no difference in the total CABG conduits placed, the number of arterial grafts used, and the high percentage of LIMA use. With respect to the outcome of bleeding, there were no Class IV bleeding events in either group. Class III bleeding occurred in 4.6% of patients in the early group versus 5.2% in the delayed group, which met the noninferiority for bleeding events. While not powered to fully assess secondary outcomes, ischemic events were not present in the early group, but occurred in 8.7% of patients in the delayed group.  At 6 months, cumulative major adverse cardiac events (MACE) were fewer in the early group when compared to the delayed group.

Many surgeons have already shifted their practice to an earlier CABG strategy based on the European guidelines and extrapolation of prior data. In a press conference after the trial results, Dr. Joanna Chikwe of Cedars Sinai Hospital in California noted the she is “comfortable going within 48 hours,” adding “I’m really glad to see this data. It confirms what I already think is safe.” Other surgeons present commented on the low power of the study given the small number of participants, but were reassured by the few events in both groups.