At present, evidence supporting the benefit of initiating dual antiplatelet therapy (DAPT) in patients undergoing CABG remains limited. In this multicenter study conducted across 22 centers in five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden), patients were randomly assigned in a 1:1 ratio to receive ticagrelor plus aspirin (DAPT group) or aspirin alone (ASA group) for 1 year following CABG indicated for ACS. A total of 2201 patients were randomized, with 1104 assigned to the DAPT group and 1097 to the ASA group.
Inclusion criteria required patients to be at least 18 years of age and to have experienced an ACS within the 6 weeks preceding an isolated primary CABG. Written informed consent and randomization were performed between 3 and 14 days after surgery. Exclusion criteria included concomitant cardiac surgery other than CABG, contraindications to any of the trial drugs, treatment with oral anticoagulants after surgery, any other indication for dual antiplatelet therapy, chronic kidney disease requiring dialysis, severe liver disease or concomitant bleeding disorders, second- or third-degree atrioventricular block in patients without a pacemaker, disabling stroke within 90 days before inclusion, prior intracranial hemorrhage, treatment with immunosuppressive agents, and treatment with strong CYP3A inhibitors.
The primary efficacy outcome, assessed as a time-to-event analysis at 1 year, was a composite of death from any cause, myocardial infarction (MI), stroke, or repeat revascularization. The key secondary outcome consisted of net adverse clinical events, defined as a composite of the primary outcome or major bleeding, with major bleeding defined as bleeding requiring hospitalization. Additional secondary efficacy outcomes included the individual components of the primary composite outcome, hospitalization for heart failure, need for repeat coronary angiography, and new-onset atrial fibrillation. The primary safety outcome was the first occurrence of major bleeding, evaluated in a time-to-event analysis at 1 year. Secondary safety outcomes included severe dyspnea and new-onset renal failure.
Preoperative platelet inhibition was discontinued before CABG in accordance with current guidelines: prasugrel 7 days before surgery, clopidogrel 5 days before, and ticagrelor 3 days before; aspirin was not discontinued.
Baseline variables and outcomes were obtained partly through national registries. In Sweden, which contributed approximately 40–45% of the study population, baseline characteristics were retrieved from the Swedish Cardiac Surgery Registry, and follow-up data were obtained from the National Patient Register. In the remaining participating countries, data were collected through structured telephone interviews conducted by trial nurses and by review of medical records. Systematic follow-up telephone calls were conducted at 1 month and 1 year after randomization to assess adherence to study medication and the occurrence of bleeding events not requiring hospitalization or episodes of dyspnea.
Baseline characteristics were well balanced between groups. The mean age was 66 years, 14.4% of patients were women, 27.5% had diabetes, and the median EuroSCORE II was 1.6%. More than half of the patients (57.6%) underwent CABG for non–ST-segment elevation myocardial infarction, 32.1% for unstable angina, and 10.2% for ST-segment elevation myocardial infarction. Among patients assigned to the DAPT group, 864 (79.7%) were adherent to ticagrelor at 1 month and only 688 (64.1%) at 1 year. In this group, 54 patients (4.9%) had switched to another P2Y12 inhibitor by 1 month, increasing to 75 patients (6.8%) at 1 year. In the ASA group, among patients with available data, adherence rates were 96.5% at 1 month and 92.3% at 1 year. In this group, 56 patients (5.1%) were receiving a P2Y12 inhibitor at 1 month and 73 (6.7%) at 1 year.
In the intention-to-treat population, the primary outcome occurred in 53 patients (4.8%) in the DAPT group and in 50 patients (4.6%) in the ASA group (p=.77). Net adverse clinical events, defined as the occurrence of a primary outcome event or major bleeding, were observed in 100 patients (9.1%) in the DAPT group and in 70 patients (6.4%) in the ASA group (hazard ratio, 1.45; 95% confidence interval [CI], 1.07 to 1.97). A first episode of major bleeding, the primary safety outcome, occurred in 54 patients (4.9%) receiving DAPT and in 22 patients (2.0%) receiving aspirin alone (hazard ratio, 2.50; 95% CI, 1.52 to 4.11). Severe dyspnea was significantly more frequent in the DAPT group, occurring in 21.9% of patients (95% CI, 19.0 to 25.1), compared with 6.8% (95% CI, 5.3 to 8.5) in the ASA group.
In prespecified subgroup analyses, no differences were observed in the incidence of the primary outcome according to age, sex, renal function, type of ACS (myocardial infarction vs unstable angina), presence of heart failure, left ventricular dysfunction, diabetes, or prior percutaneous coronary intervention (PCI). Finally, in the hierarchical analysis of secondary outcomes, treatment with DAPT was not associated with a greater number of wins compared with aspirin alone (win ratio, 0.54; 95% CI, 0.46 to 0.64).
The main findings of the study indicate that 1 year of treatment with ticagrelor plus aspirin after CABG did not reduce the incidence of the composite outcome of death, myocardial infarction, stroke, or repeat coronary revascularization compared with 1 year of aspirin monotherapy in patients undergoing CABG for ACS. Moreover, the study provides evidence of an increased risk of major bleeding associated with DAPT.
Current European and U.S. guidelines recommend dual antiplatelet therapy for patients with ACS who undergo CABG. However, the evidence supporting these recommendations is largely extrapolated from trials conducted in non-CABG populations, subgroup analyses of ACS trials, observational studies, and small randomized trials including mixed populations of patients undergoing CABG with or without ACS.
Consistent with the present findings, several meta-analyses and large registry-based observational studies have also reported a lack of benefit in reducing ischemic events together with an increased risk of bleeding associated with DAPT after CABG. In contrast, a randomized trial conducted in China assigned 500 patients undergoing CABG (63% with ACS) to 12 months of treatment with ticagrelor plus aspirin, ticagrelor alone, or aspirin alone. At 1 year, saphenous vein graft patency was superior in the DAPT group, and at 5 years, a reduction in clinical events was observed. In this regard, the authors of the present study report that graft patency will be assessed at 12 to 36 months in a subpopulation of 360 patients, along with a planned 10-year follow-up to determine whether improved graft patency translates into a long-term reduction in clinical events in the DAPT group.
The most relevant limitations of the study are several. The incidence of the primary efficacy outcome was lower than anticipated, which may have reduced the statistical power to detect small differences between groups. Nonadherence to ticagrelor was substantial, with approximately one third of patients assigned to DAPT discontinuing treatment before 1 year, likely related to the need for oral anticoagulation or the occurrence of bleeding or dyspnea. This degree of nonadherence may have attenuated the observed treatment effect in the intention-to-treat analysis. In addition, the trial was partially conducted during the coronavirus disease 2019 pandemic, which contributed to an unusually prolonged enrollment period.
COMMENTARY:
This study provides substantial clarity regarding the long-standing dilemma of whether a second antiplatelet agent should be systematically added after coronary surgery when the indication for revascularization is ACS. The answer emerging from these data appears to be a clear no: patients treated with DAPT experienced a similar incidence of the primary ischemic endpoint but a significantly higher rate of adverse effects, predominantly major bleeding and dyspnea.
Beyond the limitations explicitly acknowledged by the authors—namely the low incidence of the primary endpoint, the prolonged recruitment period related to the COVID-19 pandemic, and the high rates of nonadherence to DAPT—additional considerations deserve attention.
Baseline characteristics and part of the outcome data were obtained from national registries which, although mandatory and apparently comprehensive, cannot achieve the same level of granularity as fully prospective, patient-by-patient data collection throughout follow-up. Moreover, the timing of DAPT initiation is not clearly specified. Informed consent was obtained between postoperative days 3 and 14, implying a wide potential range for the initiation of ticagrelor. Whether delayed initiation may attenuate antithrombotic benefit or, conversely, whether very early initiation increases bleeding risk during the most vulnerable postoperative period remains unknown. Furthermore, follow-up was limited to 1 year, and—as highlighted by the investigators themselves—longer-term follow-up is required to determine whether potential benefits related to improved graft patency might offset the excess of early adverse events.
The limitation of nonadherence to DAPT should be viewed as an intrinsic and largely unavoidable issue with this therapeutic strategy. Even if the most frequent cause of postoperative anticoagulation—postoperative atrial fibrillation—is minimized, a proportion of patients will inevitably require oral anticoagulation during the first postoperative year. Therefore, any antithrombotic benefit associated with DAPT must be sufficiently robust to compensate not only for the increased bleeding risk but also for the substantial proportion of patients in whom DAPT will need to be discontinued. From this perspective, future studies should strongly emphasize the systematic implementation of strategies aimed at preventing postoperative atrial fibrillation—such as routine posterior left pericardiotomy, early reinstitution of beta-blockers, and selective prophylactic use of amiodarone—to reduce the need for anticoagulation, improve adherence to DAPT during the first postoperative year, and ultimately limit bleeding complications.
Although the present data clearly indicate that DAPT is not beneficial as a universal strategy during the first year after CABG in patients presenting with ACS, there is some evidence suggesting that DAPT may improve saphenous vein graft patency, likely through a reduction in thrombotic events. Consequently, patients at particularly high risk of vein graft thrombosis or recurrent ischemic events—such as those with dilated or varicose saphenous veins, small-caliber conduits, borderline graft flow, diffuse coronary disease with poor distal runoff, distal coronary disease beyond the anastomoses, or incomplete revascularization—may derive greater benefit from this approach. Focused randomized studies in these high-risk subgroups could potentially demonstrate a more favorable risk–benefit balance, supporting a selective rather than generalized use of DAPT after CABG.
In conclusion, the routine use of DAPT after CABG for ACS should not be generalized to all patients. Additional evidence will depend on the long-term follow-up of the present trial and on future randomized studies specifically targeting patient subgroups with the highest thrombotic risk.
REFERENCE:
Jeppsson A, James S, Moller CH, Malm CJ, Dalén M, Vanky F, et al.; TACSI Trial Group. Ticagrelor and aspirin or aspirin alone after coronary surgery for acute coronary syndrome. N Engl J Med. 2025;393:2313–2323. doi:10.1056/NEJMoa2508026.
