MADRID — The duration of dual antiplatelet therapy (DAPT) in patients with myocardial infarction (MI) should be shortened from 1 year to 3 months, according to data from a new randomized, real-world trial. 

In the DUAL-ACS trial, giving DAPT for the first 3 months after MI and then continuing with single antiplatelet therapy was associated with a strong trend towards lower all-cause mortality than continuing with DAPT for 12 months. 

The principal secondary endpoint, cardiovascular death or recurrent MI, did not differ between the two groups, but researchers observed a strong trend towards an increase in major bleeding in patients who received 12 months of DAPT. 

Unfortunately, the trial was underpowered due to recruitment issues during the COVID-19 pandemic, and none of the results reached significance. But lead author David Newby, MD, chair of cardiology at the University of Edinburgh in Edinburgh, Scotland, pointed out that these results were consistent with previous studies and meta-analyses, building the case for shorter durations of DAPT after MI. 

“In the absence of demonstrable benefits and real concern of harm, I believe that less is more, and patients should be treated with DAPT for only 3 months after an MI,” Newby said. “This will avoid potentially harmful, and even fatal, side effects of these powerful antithrombotic therapies, while maximizing the benefit.” 

Newby presented the DUAL-ACS trial at the European Society of Cardiology (ESC) Congress 2025.

A Burning Issue

Robert Byrne, MD, director of cardiology at the Mater Private Hospital in Dublin, Ireland, and cochair of the session during which DUAL-ACS was presented, said the question of DAPT duration is a burning issue in clinical practice. 

“Many of the studies looking at shorter durations of DAPT have been done in Asian populations, and there are concerns about generalizability. We have been waiting for a trial like this to help us. I think we’re accumulating lots of data suggesting that different types of DAPT de-escalating strategies seem to be very attractive in these modern days,” he said.

In his presentation, Newby said some meta-analyses raise concerns that longer durations of DAPT may be causing harm, even an increase in all-cause mortality. Despite this, the current European and North American guidelines give a 1A recommendation for 12 months of DAPT for patients after an MI, unless they have a high bleeding risk. 

He reminded the audience that the CURE trial of clopidogrel on top of aspirin, the first ever key trial of DAPT conducted 25 years ago, showed that the benefit of clopidogrel occurred mainly in the first 3 months and diminished from 3 to 12 months, with an ongoing background bleeding risk.

Since then, many trials have examined optimal DAPT duration, but most have evaluated treatment in patients with drug-eluting stents. Meta-analyses have also suggested that longer durations of therapy are associated with harm, and shorter durations have lower bleeding and mortality risks, according to Newby.

He also pointed out that patients enrolled in these DAPT trials are generally not at high risk for bleeding, but in real-world practice, physicians often treat higher-risk patients.

“We don’t always use the same rigor of checking the multiple exclusion criteria to make sure the patient is not at increased bleeding risk, and so when you look at the bleeding rates in real-world data, they are substantially higher,” he said.

“Most DAPT duration trials have been done in stented patients, predominantly with stable chest pain. There has never been a trial of duration of DAPT therapy in all-comer MI patients. And there’s a real concern that in the real world, patients at a higher risk for bleeding are being treated, and maybe the benefit-risk ratio is not there,” he added.

Newby and colleagues conducted the DUAL-ACS trial to address the question of optimal DAPT duration in a large population of real-world patients with MI.

The trial aimed to enroll 17,000 patients but was terminated after only enrolling 5000 patients because of slow recruitment during the COVID-19 pandemic. 

These patients were mainly from Scotland and were predominantly White. They had a mean age of 63 years, 73% were men, and they had a range of cardiovascular risk factors characteristic of a population with MI, Newby reported. Around 25% of patients were managed medically, two thirds underwent percutaneous coronary intervention, and 6%-7% underwent bypass surgery. 

Newby and colleagues randomly assigned patients who were, on average, 2 days post-MI to 3 or 12 months of DAPT with aspirin plus a P2Y12 inhibitor, mostly clopidogrel or ticagrelor. They ascertained clinical events on follow-up using medical records.

The primary endpoint of all-cause death was numerically lower with shorter DAPT duration, occurring in 2.7% of patients on 3 months of DAPT vs 3.4% of those on 12 months of DAPT (hazard ratio [HR], 0.78; P = .12). Results revealed a very similar numerical reduction in cardiovascular death. 

The principal secondary endpoint of cardiovascular death or nonfatal MI was similar in the two groups — 9.3% in patients on 3 months of DAPT and 8.9% in those on 12 months of DAPT (HR, 1.04; P = .61). 

The main safety endpoint, fatal or major nonfatal bleeding, was numerically reduced in the 3-month DAPT group (3.2% vs 4.0%; HR, 0.78; P = .097). 

“While we did not see any statistically significant differences, because the trial was stopped early and was therefore very underpowered, the trends are very consistent with what we know today in terms of the effects of more prolonged DAPT,” Newby concluded.

A Need to Revisit the Guidelines

Newby placed the DUAL-ACS data in context.

“These results beg the question of why we would give DAPT for 12 months? There’s no evidence of efficacy, and there are signals of harm. Surely, we need to revisit our guideline recommendations on this,” he said. 

During a discussion of the trial, Stefan James, MD, professor of cardiology at Uppsala University in Uppsala, Sweden, noted that some previous studies using prasugrel or ticagrelor as the second antiplatelet agent in combination with aspirin suggest a continued reduction in events up to a year vs aspirin alone, which is why the guidelines recommend approximately 12 months of treatment despite the expense of increased bleeding. 

Many trials have addressed different antithrombotic strategies and therapies, mainly in stented patients, and several meta-analyses have suggested that 12 months or longer of DAPT increases bleeding, but shorter durations may be linked to a higher risk for stent thrombosis and MI, according to James.

“So that prompts the question: Which is worse for patients — an MI or a bleed? Looking at all-cause mortality is the only way of addressing this question properly, and that is what the DUAL-ACS trial did,” he said.

He noted the trial had a very pragmatic design that included a very relevant population representative of the patients who physicians see in daily clinical practice. 

And although the results were not significant, the numerical differences suggested a lower rate of mortality with a shorter duration of DAPT, accompanied by a numerically slightly higher incidence of MI or stent thrombosis, as expected, James said.

Noting that most patients in this trial in the 3-month DAPT group stopped the P2Y12 inhibitor and continued on aspirin alone, James said the alternative strategy of stopping aspirin and continuing the P2Y12 inhibitor has been associated with better outcomes. And while 12 months of DAPT is the default position in the ESC guidelines, they do mention alternative de-escalating strategies in patients at high risk for bleeding.

“I think the trial points towards the large number of studies showing that a short duration of DAPT and then stopping aspirin would be the most attractive way going forward. Future guidelines committees may consider several of these de-escalating strategies that have been shown to reduce bleeding risk or net clinical outcomes, and some of which also appear to reduce mortality,” he said. 

The DUAL-ACS trial was funded by the University of Edinburgh, the NHS Lothian Health Board, Scotland, and the British Heart Foundation. Newby reported having no relevant conflicts of interest.