Optimizing antiplatelet therapy after coronary artery bypass graft: selection, dosing, and duration

Antiplatelet therapy is imperative for the management of coronary artery disease (CAD). Dual antiplatelet therapy (DAPT) after coronary artery bypass graft (CABG) surgery is associated with a reduction in the incidence of major adverse cardiac events over 5 years (1). In secondary prevention, antiplatelet therapy prevents plaque thrombosis and subsequent cardiovascular events by inhibiting platelet aggregation. Following CABG surgery, helps prevent early vein graft occlusion caused by endothelial damage and graft thrombosis, and also leads to improvement in long-term graft patency (2-4). Antiplatelet therapy thus plays a major role in improving saphenous vein grafts (SVGs) patency which are used in over 90% of CABG surgeries (5). While aspirin alone has not been proven to improve the patency of arterial grafts, it may help prevent or slow down atherosclerosis in distal native coronary arteries or those not grafted, especially in diabetic patients (6,7). Therefore, aspirin therapy benefits all CABG patients, regardless of the types of graft used.

Aspirin [acetylsalicylic acid (ASA)] is the cornerstone of antiplatelet therapy following CABG, effectively reducing adverse cardiovascular events and graft failure (4). Administering aspirin within 6 hours post-CABG can improve early graft patency and long-term outcomes, including reduced mortality, myocardial infarction, stroke, and renal insufficiency (8). Although daily doses between 75 and 325 mg are common, the optimal dosing strategy for aspirin in this setting remains an area of ongoing research. A meta-analysis has suggested that high doses ASA (300 to 325 mg daily) is associated with improved graft patency compared to low-dose ASA (50 to 100 mg daily) (9).

In higher-risk patients, DAPT is recommended and has been shown to provide stronger platelet inhibition (10,11). DAPT, includes aspirin combined with an oral P2Y12 receptor inhibitor like clopidogrel, ticagrelor, and prasugrel. Prasugrel and ticagrelor have a more rapid onset of action, and provide stronger and more consistent platelet inhibition, compared to clopidogrel (12). However, the benefit of DAPT after CABG remains a subject of debate. Research comparing DAPT with ticagrelor vs. aspirin has produced inconsistent and underpowered findings (13-15).

Currently, DAPT is recommended for a period of one year after off-pump CABG. This involves combining ASA (81 mg) with clopidogrel (75 mg) to lower the risk of graft occlusion (Class I, Level of Evidence A) (4,16). DAPT is advised for CABG patients who are already receiving it due to acute coronary syndrome (ACS). However, for stable CAD patients without a prior history of percutaneous coronary intervention (PCI) with stent placement, the evidence supporting DAPT use is insufficient. The Arterial Revascularization Trial did not demonstrate any difference in the major adverse cardiovascular events (MACE) rates one year after CABG between patients on aspirin alone and those on DAPT (7). Additionally, a meta-analysis by Chakos et al., involving 2,133 CABG patients, found no notable difference in graft patency between the two treatment strategies, although DAPT was linked to higher rates of surgical bleeding (2).

Ticagrelor has also been evaluated in another meta-analysis that reported that DAPT using ticagrelor was associated with a significant reduction in SVG failure but also resulted in a higher incidence of clinically significant bleeding when compared to using ASA in isolation (17). However, the POPular CABG (18) and TAP-CABG (19) trials did not demonstrate notable differences in graft occlusion rates between ticagrelor DAPT and aspirin at 1 year and 3 months post-surgery, respectively. Additionally, a network meta-analysis also failed to demonstrate a difference regarding bleeding events with either strategy (20). Another meta-analysis, which included five randomized controlled trials (RCTs) and 3,996 patients, similarly found no substantial difference in bleeding risk between ticagrelor-based antiplatelet therapy and aspirin or clopidogrel (21).

Thus, the recent paper on the 5-year follow-up results from the DACAB trial has offered strong evidence for the most effective antiplatelet approach after CABG (22). This multicenter, randomized study evaluated the use of ticagrelor DAPT, ticagrelor alone, and aspirin alone for 1 year after surgery, followed by standard care. The trial’s primary outcome—MACE at the 5-year mark—revealed notable advantages of ticagrelor DAPT over both ticagrelor and aspirin monotherapy. The results highlight several key clinical implications. Firstly, DAPT using ticagrelor exhibited a significant reduction in MACE rates compared to those receiving aspirin alone (22.6% vs. 29.9%). Secondly, a similar, though slightly smaller, risk reduction was observed when compared to ticagrelor monotherapy (22.6% vs. 32.9%). These findings remained consistent across different sensitivity analyses, confirming the strength and reliability of the original outcomes. The study’s design, which includes a broad patient base from various Chinese tertiary hospitals, enhances the applicability of its findings across different populations. Strong adherence to the randomized treatment during the first year, coupled with thorough follow-up over 5 years, adds to the robustness of the study. Nevertheless, some limitations must be acknowledged. The trial was not specifically designed to assess clinical outcomes, potentially impacting the statistical power of certain secondary endpoints. Furthermore, antiplatelet therapy adjustments beyond the first year were left to clinical judgment, which may have introduced variability in the long-term results.

In summary, the DACAB trial presents compelling evidence for the use of ticagrelor DAPT during the first year after CABG to lower the risk of MACE over 5 years. These findings have important clinical implications and could influence future guidelines for post-CABG antiplatelet therapy. Further research should focus on the safety and effectiveness of extended DAPT beyond the initial year post-surgery. This research offers valuable insights into optimizing outcomes following CABG and encourages a reevaluation of current antiplatelet therapy strategies in this patient group.

Acknowledgments

Funding: None.

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