No penalty to early CABG after stopping ticagrelor

Undergoing CABG* within 2 to 3 days after stopping the antiplatelet ticagrelor does not increase the risk of severe/massive bleeding compared with delaying surgery until 5 to 7 days of ticagrelor discontinuation in patients with ACS**, according to the RAPID CABG *** study presented at AHA 2021. 

Furthermore, patients who waited longer before surgery experienced more ischaemic events and required a longer hospital stay, reported lead investigator Professor Derek So from the University of Ottawa in Ottawa, Canada.

Ticagrelor is widely used in patients with ACS, he explained. However, about 10 percent of patients presenting with ACS need to undergo CABG, which comes with the risk of perioperative bleeding particularly in patients on antiplatelet therapy.

Undergoing CABG within 24 hours of stopping ticagrelor has previously been shown to be associated with increased mortality in the PLATO trial, So noted. As such, North American guidelines currently advocate waiting for at least 5 days after ticagrelor discontinuation before CABG, while the European guidelines recommend a waiting period of at least 3 days.

Nonetheless, these guidelines recommendations are based on cohort studies and pharmacodynamics data rather than randomized evidence. “RAPID CABG is the first and only randomized controlled trial evaluating the safety of early surgery in patients taking ticagrelor,” So said.

CABG: Rapid or delayed?

In the physician-initiated multicentre study, 143 patients presenting with ACS who were taking ticagrelor and required non-urgent bypass surgery were randomized to undergo early surgery within 2–3 days after stopping ticagrelor (n=71; mean age 63.2 years, 80.3 percent male) or delayed surgery after a waiting period of 5–7 days (n=69; mean age 64.7 years, 82.6 percent male). [AHA 2021, LB session 1]

“We discovered no significant increase in bleeding when people had bypass surgery after 2-3 days of discontinuing ticagrelor,” So reported. “These findings may be surprising based on the assumption that the presence of a strong blood thinner should predispose people to severe bleeding.”

Early surgery was noninferior to delayed surgery for the primary outcome of severe/massive perioperative bleeding, as defined by the UDPB^# class 3 or 4, which occurred in 4.6 percent vs 5.2 percent of patients, respectively (p=0.0253 for noninferiority).

There were also no differences in other bleeding outcomes, as defined by TIMI CABG (two patients vs none), BARC^## Type 4 (two patients vs none) or Type 5 bleeding (none in both arms).

Ischaemic events, by contrast, were more common in the delayed surgery group than the early surgery group. While there were no presurgical ischaemic events in the early surgery group, six such events had occurred in the delayed CABG group, which comprised one myocardial infarction event, four recurrent ischaemic cases, and one episode of ventricular tachycardia.

In addition, patients in the early CABG group required shorter length of hospital stay than those who received CABG later (median, 9 vs 12 days).

“I’m really glad to see this data. It confirms what I think is safe,” said Dr Joanna Chikwe from the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, California, US, who claimed that she is  “comfortable going within 48 hours [in practice].”

“[The] trial was helpful, and although it confirms my practice, I think physicians may want to see a larger-powered trial to be convincingly compelled that they should change their practice,” Chikwe noted. 

In agreement, So said, “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.”

*CABG: Coronary artery bypass graft surgery
**ACS: Acute coronary syndrome
***RAPID CABG: A randomized study of early versus standard coronary artery bypass surgery among patients presenting with acute coronary syndromes treated with ticagrelor
^#UDPB: Universal Definition of Perioperative Bleeding
^##BARC: Bleeding Academic Research Consortium