Loading ...

MADRID — New data from two randomized trials suggest that dual antiplatelet therapy (DAPT) should be significantly shortened or not used at all after coronary artery bypass surgery (CABG).

The TACSI trial, conducted in four Nordic countries, showed no difference in ischemic cardiovascular events but an increase in bleeding among patients with acute coronary syndrome (ACS) treated with CABG who received 12 months of aspirin plus ticagrelor compared with those who received aspirin alone.

Researchers for the TOP-CABG trial, conducted in China in patients who underwent elective CABG, also found that 3 months of DAPT was associated with similar vein graft occlusion rates while significantly reducing risk for clinically relevant bleeding compared with 12 months of DAPT.

The two trials were presented at the European Society of Cardiology (ESC) Congress 2025, and results from the TACSI trial were simultaneously published online in The New England Journal of Medicine.

“These results question current guidelines, which recommend 12 months of DAPT in patients undergoing CABG after ACS,” Anders Jeppsson, MD, of the Sahlgrenska University Hospital in Gothenburg, Sweden, who led the TACSI trial, said during a presentation of the data.

Likewise, TOP-CABG investigator Xin Yuan, MD, of Fuwai Hospital in Beijing, China, said, “In our opinion, 3-month DAPT after CABG gives a smarter, more targeted standard of care compared with 12 months.” 

TACSI Trial

During his presentation, Jeppsson questioned the evidence backing current guidelines that recommend 12 months of DAPT for patients with ACS treated with CABG.

“These guidelines are based on very thin data, I would say, mainly extrapolation of data from non-CABG trials and small randomized trials with surrogate endpoints, and the compliance to the recommendation is poor,” he said.

For the open-label, registry-based TACSI trial, 2201 patients from 22 Nordic centers who underwent CABG for ACS were randomly assigned to receive DAPT with ticagrelor plus aspirin or aspirin alone for 1 year.

The primary outcome, a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year, occurred in 4.8% of the DAPT group and 4.6% of the aspirin-alone group, a difference that was nonsignificant (hazard ratio [HR], 1.06; 95% CI, 0.72-1.56).

Major bleeding, however, was significantly increased in the DAPT group (4.9%) compared with the aspirin-alone group (2.0%), with an HR of 2.50 (95% CI, 1.52-4.11).

Net adverse clinical events, defined as a primary outcome event or major bleeding, were also significantly increased in the DAPT group (9.1% vs 6.4%; HR, 1.45; 95% CI, 1.07-1.97).

Trial limitations included a lower event rate than expected and low adherence to study medication, especially in the DAPT group. One third of those patients had discontinued study treatment at 1 year, which may have been attributable to initiation of oral anticoagulants, dyspnea, and bleeding episodes.

The researchers are following the patients for up to 10 years. Jeppsson noted this longer follow-up is important in light of a Chinese study showing no difference in clinical endpoints but better graft patency with DAPT after 12 months.

“After 5 years, there was a difference in clinical events, so we need to follow these patients a bit longer before we make any final conclusions,” Jeppsson said.

“This is really very interesting because the ACS guidelines recommend 12 months of DAPT for patients who receive a percutaneous coronary intervention (PCI), and this was simply extrapolated to CABG with no real evidence in this population,” Dan Atar, MD, a professor of cardiology at the Oslo University Hospital in Oslo, Norway, said during a discussion of the findings at a press conference.

“Even in PCI patients there’s a move now towards shorter-term DAPT, so it is extremely enlightening to see these results, and they will definitely be discussed heavily in our community,” he said.

Jeppsson pointed out that there are biological reasons why DAPT might be too much in CABG patients.

“If you stent the patient, they would be in need of a stronger, more effective antiplatelet regimen, but in CABG, we don’t leave anything in the coronaries to cause thrombosis, so DAPT may not be necessary,” he said.

‘No Clear Role for Routine DAPT’

During a discussion of the TACSI trial, John Eikelboom, MBBS, of McMaster University in Hamilton, Ontario, Canada, pointed out that the rate of major adverse cardiovascular events in CABG patients is around 10% and graft failure, which is a known predictor of clinical events, affects around 15%-20% of patients by 12 months after the procedure.

Historical data indicate that aspirin is effective in preventing these events, showing around a 50% reduction in graft failure and a 20% reduction in major adverse cardiovascular events, according to Eikelboom.

Moderate-quality evidence suggesting that adding another antiplatelet agent to aspirin reduces graft failure exists, but whether this also reduces cardiovascular outcomes remains unknown, he said.

“The TACSI results are clear and simple. There is now moderate-quality evidence at 12 months that the combination of ticagrelor and aspirin in CABG patients with recent ACS does not improve clinical outcomes, but it increases bleeding, and the results were consistent across different endpoints and in various subgroups,” Eikelboom said, noting that this addresses an important unresolved question.

“This is one of the largest trials in this field, and its pragmatic design means that this therapy was evaluated in a real-world clinical setting. However, the high ticagrelor discontinuation rate and the low event rate limited the power of the trial, reflected by the wide 95% confidence intervals for clinical events,” he said.

Regarding the trial’s implications for clinical practice, Eikelboom recommended that aspirin remain the standard of care after CABG.

“There is no clear role for routine DAPT, although this may be considered in selected patients to maintain graft patency,” he said.

Eikelboom wondered how these results can be reconciled with evidence that DAPT reduces graft failure and that graft failure predicts clinical events. He said he welcomes the extended follow-up of patients in the trial, which may clarify whether the better graft patency might translate into long-term clinical benefits.

TOP-CABG Trial

During his presentation of TOP-CABG, Yuan noted that there is “robust and clear” evidence that DAPT significantly improves vein graft patency over aspirin alone, although the increased risk for bleeding presents a dilemma.

In the PCI setting, the latest approaches focus on using intensive DAPT for the first 1-3 months — the period during which thrombotic risk is highest — and then de-escalating, according to Yuan. He noted a similar approach in CABG may preserve vein graft protection while significantly reducing bleeding risk.

To investigate this further, Yuan and colleagues randomly assigned 2300 elective CABG patients to 1 year or 3 months of DAPT followed by 9 months of aspirin alone.

The primary outcome was vein graft occlusion at 1 year. The primary safety outcome was clinically relevant bleeding.

Results showed that vein graft occlusion at 1 year was similar in the two groups — 10.8% in the 3-month DAPT group and 11.2% in the 1-year DAPT group — but bleeding was lower in those treated for 3 months than in those treated for 1 year (8.3% vs 13.2%; P < .001).

“Our take-home message is that 3-month DAPT reduces bleeding risk and offers a better balance between ischemic protection and safety,” Yuan said.

Aspirin-Only Arm Needed

During a discussion of the TOP-CABG trial, Marco Valgimigli, MD, of the Cardiocentro Ticino Institute in Lugano, Switzerland, noted three studies have suggested that aspirin plus ticagrelor reduces graft vein occlusion, but this benefit comes at the cost of an increased bleeding risk.

He also said a meta-analysis of the data from those three studies showed “absolutely no hint towards a possible clinical benefit with DAPT.” 

“TOP-CABG is truly a top study. It brings clear results. Twelve-month DAPT makes the patient bleed; 3-month DAPT is apparently as good as 12 months, with lower bleeding complications,” Valgimigli said.

However, he thought the inclusion of an aspirin-only arm would have improved the study.

“Another point which is not entirely clear is whether vein graft patency is truly a convincing endpoint, especially taking into account the apparently discrepant findings between graft patency and clinical outcomes,” Valgimigli noted.

On when vein graft occlusion actually occurs, he pointed out that studies suggest two components of occlusion. One mechanism is immediate and related to the CABG procedure, which likely could be related to thrombosis, and the second seems to be more linear over time and potentially may not be so related to thrombosis.

“After this trial, I will no longer give 12 months of DAPT to my chronic coronary syndrome patients after CABG. I may opt for 3-month DAPT in selected patients, especially if the patient is at low bleeding risk. But I would like to see another study of aspirin monotherapy vs DAPT for 3 months in chronic coronary syndrome patients after CABG,” he concluded.

TACSI was an investigator-initiated trial and was funded by the Swedish Research Council, the Swedish Heart Lung Foundation, and the Swedish state. The TOP-CABG trial was funded by the National Clinical Research Centre for Cardiovascular Diseases in China. Jeppsson and Yuan reported no conflicts of interest.