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Commentary: Ticagrelor monotherapy—Not for CABG?

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Saphenous vein grafts (SVGs) remain the most commonly used conduits in coronary artery bypass grafting (CABG) despite greater rates of both early and late occlusion compared to arterial grafts. In… Click to show full abstract

Saphenous vein grafts (SVGs) remain the most commonly used conduits in coronary artery bypass grafting (CABG) despite greater rates of both early and late occlusion compared to arterial grafts. In a recent meta‐analysis based on aggregate data from 48 studies including 41,530 grafts, the pooled incidence of SVG occlusion within the first year after CABG was estimated at 11%. The role of aspirin in the prevention of SVG failure has been firmly established. Fremes et al. in a meta‐analysis of 17 randomized trials showed that aspirin significantly reduced graft occlusion compared with placebo. A subsequent systematic review of seven studies concluded that administration of aspirin within 6 h of CABG was associated with improved graft patency without increased incidence of bleeding complications. Dual antiplatelet therapy (DAPT) combining aspirin with a P2Y12 inhibitor has since been shown to be the most efficacious treatment regimen to prevent SVG failure, although at the expense of greater bleeding risk. The excess of bleeding events with DAPT has generated interest in the use of antithrombotic approaches that do not include aspirin. In this issue of The Journal of Cardiac Surgery, Kulik et al. present the results of the randomized Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET) trial. TARGET randomized 250 patients after CABG to receive either aspirin 81mg twice daily or ticagrelor 90mg twice daily. The primary outcome of SVG occlusion at 1 year as assessed by computed tomography angiography did not differ significantly between the two groups (aspirin vs. ticagrelor, 17.4% vs. 13.2%, p = .30). The secondary outcome of SVG disease, defined as either stenosis >50% or occlusion, also did not show any difference between the randomized treatments (aspirin vs. ticagrelor, 21.5% vs. 22.3%, p = .88). These results are not entirely unanticipated, given previous reports on the lack of a conclusive benefit of ticagrelor monotherapy on SVG patency in the Different Antiplatelet Therapy Strategy after Coronary Artery Bypass Graft Surgery (DACAB) trial, as well as on clinical outcomes in patients undergoing CABG in the Ticagrelor in CABG (TiCAB) trial. The ticagrelor monotherapy arm of the DACAB trial failed to demonstrate a significant difference in SVG patency at 1 year compared with aspirin, although the combination of aspirin and ticagrelor did result in a significant increase in SVG patency. However, 76% of patients in DACAB underwent off‐pump CABG (OPCAB), a subgroup for whom a benefit of DAPT using clopidogrel has previously been demonstrated. In the TARGET trial, patients undergoing OPCAB also did not benefit from more potent platelet inhibition provided by ticagrelor. A transient increase in platelet turnover after CABG that limits the duration of platelet TXA2 inhibition has been proposed as the mechanism for the impaired efficacy of low‐dose aspirin observed in the early postoperative period. Multiple daily doses of aspirin may overcome impaired platelet inhibition in response to a conventional once‐daily regimen, and may have contributed to a lack of advantage of ticagrelor over aspirin in the current trial. It should be noted, however, that two of the three randomized trials to date evaluating ticagrelor monotherapy (TARGET and TiCAB) were terminated prematurely due to slow enrollment and were individually underpowered to detect a difference in the treatment effect over aspirin, precluding conclusive evidence

Keywords: trial; ticagrelor monotherapy; cabg; ticagrelor; occlusion

Journal Title: Journal of Cardiac Surgery
Year Published: 2022

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