Ticagrelor Plus Aspirin Versus Aspirin Alone After Coronary Artery Bypass Grafting in Acute Coronary Syndrome: A Contemporary Evidence Synthesis

Highlights

• Recent large-scale randomized evidence (TACSI trial, 2025) indicates no incremental benefit of ticagrelor added to aspirin in reducing major cardiovascular events after CABG for acute coronary syndrome compared to aspirin alone.
• The combination strategy significantly increases major bleeding risk and net adverse clinical events, cautioning against routine dual antiplatelet therapy post-CABG in this setting.
• Current data emphasize the need to individualize antiplatelet regimens post-CABG, balancing ischemic risk and bleeding potential.

Background

Acute coronary syndrome (ACS) remains a leading cause of morbidity and mortality globally, frequently necessitating coronary artery bypass grafting (CABG) when revascularization is indicated. Postoperative antiplatelet therapy forms the cornerstone for preventing graft occlusion and adverse cardiovascular events. Aspirin monotherapy is established as standard of care, with well-documented efficacy in improving graft patency and reducing thrombotic complications.

Given the efficacious platelet P2Y12 inhibition by ticagrelor demonstrated in ACS patients treated medically or percutaneously, the extension of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin post-CABG has been hypothesized to further reduce thrombotic events. However, the optimal antiplatelet strategy in CABG patients, especially those surgically revascularized for ACS, remains unresolved due to scarce randomized data and concerns about bleeding complications.

Key Content

Chronological Development and Prior Evidence

Early evidence supporting aspirin use post-CABG dates back several decades, with randomized trials consistently demonstrating its benefit in reducing graft thrombosis and ischemic events. Dual antiplatelet therapy after percutaneous coronary intervention (PCI) in ACS is well-established, benefiting from trials such as PLATO (ticagrelor) and CURE (clopidogrel).

Limited prior randomized data addressed DAPT after CABG. Observational and smaller-scale randomized studies showed mixed results, with potential modest ischemic benefits offset by bleeding risk. Guidelines have variably recommended aspirin monotherapy or DAPT in selected patients, leading to heterogeneity in clinical practice.

Efficacy and Safety Evidence: The TACSI Trial (Jeppsson et al, NEJM 2025)

The TACSI trial is a pivotal, registry-based randomized clinical trial conducted across 22 Nordic thoracic centers encompassing 2201 patients undergoing CABG for ACS. Patients were randomized 1:1 to ticagrelor plus aspirin versus aspirin alone for one-year postoperatively. The primary composite endpoint included death, myocardial infarction, stroke, or repeat revascularization.

Key findings after one year were:

• No significant difference in the primary composite endpoint between ticagrelor plus aspirin (4.8%) and aspirin alone groups (4.6%) (hazard ratio [HR] 1.06; 95% CI 0.72–1.56; P=0.77).
• Net adverse clinical events (primary endpoint or major bleeding) were significantly higher in the ticagrelor-plus-aspirin group (9.1%) compared to aspirin alone (6.4%) (HR 1.45; 95% CI 1.07–1.97).
• Major bleeding was more than doubled with ticagrelor plus aspirin (4.9%) versus aspirin alone (2.0%) (HR 2.50; 95% CI 1.52–4.11).

The study was adequately powered and pragmatic in design, with rigorous follow-up and adjudication of events, lending strong internal and external validity.

Comparative Data and Meta-Analyses

A recent meta-analysis aggregating data from multiple randomized trials and observational studies corroborates the TACSI findings, showing no mortality or myocardial infarction reduction with ticagrelor-based DAPT post-CABG but an increased bleeding risk. These data suggest that platelet inhibition intensity beyond aspirin alone may not confer clinically meaningful arterial graft protection or cardiovascular event reduction.

Expert Commentary

The TACSI trial importantly addresses a critical clinical equipoise regarding DAPT after CABG in ACS patients. While strong P2Y12 inhibition benefits patients managed with PCI, the surgical milieu with arterial and venous grafts, differences in thrombotic milieu, and perioperative bleeding risk complicate extrapolation.

Biologically, platelet activation post-CABG is partly surgical trauma-related and evolves differently than plaque rupture–driven thrombosis in ACS. Aspirin’s irreversible cyclooxygenase inhibition adequately mitigates prostaglandin-mediated platelet aggregation, possibly explaining the lack of added benefit from dual inhibition.

The increased bleeding risk with ticagrelor plus aspirin underscores the need for careful patient selection, especially because bleeding events post-CABG can impair recovery and increase morbidity.

Guidelines (e.g., ESC, ACC/AHA) may reconsider routine DAPT post-CABG in ACS, emphasizing aspirin monotherapy unless specific indications (e.g., recent PCI, high thrombotic risk) warrant intensified antiplatelet regimens.

Limitations include the open-label design and underrepresentation of women (14.4%), which warrants cautious extrapolation. Future studies might explore personalized approaches incorporating platelet function testing or biomarkers to identify subgroups who might benefit from intensified therapy.

Conclusion

Contemporary high-quality evidence, led by the 2025 TACSI trial, indicates that ticagrelor plus aspirin does not reduce the incidence of death, myocardial infarction, stroke, or repeat revascularization compared to aspirin alone in patients undergoing CABG for acute coronary syndrome. The significant increase in major bleeding and net adverse clinical events with dual therapy calls for a tailored approach to antiplatelet management post-CABG.

Aspirin monotherapy remains the cornerstone of antiplatelet therapy post-CABG in ACS. Clinical decision-making should weigh ischemic risk against bleeding and consider patient-specific factors, procedural details, and co-morbidities.

Future research should focus on refining patient selection for intensified antiplatelet regimens and exploring novel agents or strategies minimizing bleeding while preventing ischemic events in this complex population.

References

• Jeppsson A, James S, Moller CH, et al; TACSI Trial Group. Ticagrelor and Aspirin or Aspirin Alone after Coronary Surgery for Acute Coronary Syndrome. N Engl J Med. 2025;393(23):2313-2323. doi:10.1056/NEJMoa2508026. PMID: 40888737.
• Local and international guidelines on antiplatelet therapy post-CABG (ESC, ACC/AHA guidelines; recent updates pending post-TACSI data).
• Meta-analyses on DAPT post-CABG from indexed randomized trials and observational data (various, referenced within recent reviews).