In patients with acute coronary syndrome (ACS) who are undergoing coronary artery bypass grafting (CABG), treatment with ticagrelor within 7 days prior to surgery is associated with lower rates of mortality after CABG and comparable rates of CABG-related bleeding compared with clopidogrel. The oral, reversibly binding P2Y₁₂ antagonist ticagrelor provides greater inhibition of platelet aggregation and a faster offset than clopidogrel, which is an irreversible platelet inhibitor. Findings from a retrospective analysis of the nonrandomized subgroup of patients who required CABG (n=1261) within 7 days of last intake of study drug from the Platelet Inhibition and Patient Outcomes (PLATO; NCT00391872) study, comparing ticagrelor and clopidogrel, were presented by Claes Held, MD, PhD, Uppsala Clinical Research Center, Uppsala, Sweden.

Current ACS guidelines recommend dual antiplatelet therapy with aspirin and clopidogrel for at least 12 months and that clopidogrel be withheld for at least 5 days prior to CABG. However, this is not always possible, as urgent situations may necessitate surgery prior to 5 days after treatment cessation.

The PLATO-CABG analysis included 1261 patients with ACS, of whom 632 were treated with ticagrelor and 629 were treated with clopidogrel. The median age was 64 years, and 81% was male. Approximately 90% of patients underwent coronary angiography at study entry, and approximately 19% underwent percutaneous coronary intervention (PCI) within 24 hours of randomization. The primary efficacy endpoint was the composite of cardiovascular (CV) death, myocardial infraction (MI), or stroke at 12 months post-CABG. The primary safety endpoint was total major bleeding (as defined according to the Global Use of Strategies to Open (GUSTO) occluded coronary arteries guidelines) from time of CABG. The secondary endpoints included the individual components of the primary efficacy endpoint (CV death, MI, and stroke) as well as all-cause mortality and non-CV death.

There was no significant difference between ticagrelor and clopidogrel therapy with regard to the composite primary efficacy endpoint (10.5% vs 12.6%; HR, 0.84; 95% CI 0.60 to 1.16; p=0.29). However, the rate of CV death was significantly lower in the ticagrelor group (4.1% vs 7.9% in the clopidogrel group; p<0.01), with most deaths occurring shortly after CABG and within the first month postprocedure (HR, 0.52; 95% CI, 0.32 to 0.85; p<0.01). The incidence of all-cause mortality was also lower in the ticagrelor group (HR, 0.49; 95% CI, 0.32 to 0.77; p=0.002). There was no reduction in the risk of MI (HR, 1.06; 95% CI, 0.66 to 1.68; p=0.82) or stroke (HR, 1.17; 95% CI, 0.53 to 2.62; p=0.70) with ticagrelor.

Overall, rates of CABG-related bleeding were high in PLATO, which Prof. Claes attributes to the bleeding definitions that were applied in the study, but these rates were not different between ticagrelor and clopidogrel (CABG-Related Major Bleeding 81.2% vs 80.1%; HR, 1.07; 95% CI, 0.80 to 1.43; p=0.67). In addition, there was no significant difference in bleeding when broken down by subtype (ie, major bleeding, life-threatening bleeding, fatal bleeding, TIMI major bleeding, TIMI minor bleeding, and GUSTO severe bleeding).

While these results suggest a reduction in CV death and all-cause mortality in ACS patients who are in need of urgent CABG, the study is a retrospective analysis of a nonrandomized post hoc subgroup, and as such, they are not conclusive, as the findings may have been affected by bias and confounding. The use of ticagrelor in these patients is not associated with an increase in major bleeding, as measured by PLATO definitions, compared with clopidogrel. The findings in the CABG cohort are consistent with the main study outcomes in terms of mortality; however, the reason for the lack of reduction in MI is unclear. A retrospective central review of the causes of post-CABG death are ongoing, as the PLATO-CABG study distinguished between vascular and nonvascular causes but did not investigate further subcategories.