MADRID — The benefits of and risks for dual antiplatelet therapy (DAPT) after percutaneous coronary intervention do not appear to be one-size-fits-all, according to two large studies.

Data from the multicenter, randomized TARGET-FIRST trial showed low-risk patients who underwent complete revascularization with percutaneous intervention can skip extended DAPT. However, results from NEO-MINDSET, a second randomized trial in a more typical population undergoing percutaneous intervention, suggested this conclusion is not generalizable.

Both studies were presented at European Society of Cardiology (ESC) Congress 2025 and published in The New England Journal of Medicine.

Are Some Antiplatelet Guidelines ‘Obsolete’?

In TARGET-FIRST, after complete revascularization in a low-risk population, researchers observed no significant increase in ischemic events but noted a reduction in bleeding events when patients who received a contemporary drug-eluting stent stopped aspirin 1 month after the procedure, according to Giuseppe Tarantini, MD, PhD, head of the Interventional Cardiology Unit at the University of Padua in Padua, Italy, who presented the findings.

Based on this large multicenter study, Tarantini argued that at least some of the current guideline recommendations for extended DAPT are “obsolete.”

This might be true, but NEO-MINDSET, a noninferiority trial that randomized a more typical population undergoing angioplasty to stop or continue aspirin within days of their procedure, did not meet its endpoint. In this trial, researchers found a reduced risk for bleeding among those who continued treatment with a potent P2Y12 inhibitor alone but also saw an increase in ischemic events in this group.

The nearly 3% increase in the composite endpoint of death from any cause, myocardial infarction, stroke, or urgent revascularization exceeded the predefined 2.5% margin for noninferiority (P = .11), according to Pedro Lemos, MD, PhD, head of interventional cardiology at Albert Einstein Israelite Hospital in Sao Paolo, Brazil, who presented the NEO-MINDSET findings.

In the investigator-initiated, multicenter, open-label TARGET-FIRST trial, 1942 patients with acute myocardial infarction who had undergone complete revascularization were randomized in 40 European sites. In one arm, patients transitioned to P2Y12 inhibitor monotherapy after 1 month of DAPT, while the others remained on aspirin plus a P2Y12 inhibitor. The choice of P2Y12 inhibitor — clopidogrel, prasugrel, or ticagrelor — was determined by the investigator.

After 11 months, Tarantini and colleagues compared the incidence of the composite primary endpoint of death from any cause, myocardial infarction, stent thrombosis, stroke, or major bleeding, as defined by a type 3 or 5 bleeding event on the Bleeding Academic Research Consortium (BARC) scale, between the two treatment arms.

All patients, about half of whom had non-ST-elevated myocardial infarction and half of whom had ST-elevated myocardial infarction, received the same contemporary biodegradable-polymer rapamycin-eluting stent. The strict exclusion criteria, which included high bleeding risk, high ischemic risk, and presence of various comorbidities, such as impaired kidney function, ensured a low-risk population.

Ischemic and Bleeding Events Lower on Monotherapy

In TARGET-FIRST, over the 11 months of follow-up, 2.1% of those in the monotherapy group vs 2.2% of those in the DAPT group had a primary event (P = .02 for noninferiority). BARC type 2, 3, or 5 bleeding events occurred in 2.6% of those on a P2Y12 inhibitor alone and 5.6% of those on DAPT (P = .002).

When considered individually, the rate of ischemic events among those randomly assigned to receive P2Y12 inhibitor monotherapy did not differ significantly from the rate among those randomly assigned to receive DAPT. This included myocardial infarction (0.7% vs 1.1%), stroke (0.3% vs 0.2%), and definite or probable stent thrombosis (0.1% vs 0%). The rates of death from any cause were 0.4% and 0.2%, respectively, according to Tarantini.

Gilles Montalescot, MD, PhD, a professor of cardiology at Pitié-Salpêtrière Hospital in Paris, France, who was invited by ESC to discuss the trial, called TARGET-FIRST another example of the disconnect between “evolving evidence and non-evolving guidelines.” He said that these data are not novel. Rather, they are supported by previous trials that suggest that there is a subset of low-risk angioplasty patients who should be considered for P2Y12 inhibitor monotherapy after an initial period of DAPT.

The appropriate length of time before switching to monotherapy is not well established across different risk factors, but Montalescot called at least 1 month of DAPT “mandatory,” regardless of risk.

Without Ischemic Noninferiority, No Conclusion for Bleeding

Despite the TARGET-FIRST findings, the results of the multicenter, open-label NEO-MINDSET trial emphasize that the individualization of antiplatelet strategies does not always mean de-escalation.

In this study, 3410 patients with successful revascularization at 50 hospitals in Brazil were randomly assigned to stop or continue aspirin within 4 days of their procedure. All patients received prasugrel or ticagrelor at the discretion of the treating physician over the following 12 months. The researchers tiered the two major endpoints. P2Y12 inhibitor monotherapy had to prove noninferior to DAPT at the end of follow-up for a composite efficacy endpoint to test superiority for the bleeding endpoint.

Due to the failure of the study to show noninferiority for the primary composite outcome of death from any cause, myocardial infarction, stroke, or urgent revascularization, the bleeding endpoint (type 2, 3 or 5 on the BARC scale) became an exploratory outcome. In fact, the reduction in bleeding in the monotherapy arm was substantial compared to that in the DAPT arm (2.0% vs 4.9%; 95% CI, -4.20 to -1.7), but it was not relevant to the study conclusion.

“Among patients with acute coronary syndromes treated with angioplasty, withdrawal of aspirin is not as protective as DAPT, even if risk of bleeding is reduced,” Lemos said.

In this study population, ST-elevated myocardial infarction was more common than non-ST-elevated myocardial infarction (62.1% vs 30.5%). Relative to TARGET-FIRST, this population was also more likely to have comorbidities, including hypertension (64% vs 39%), diabetes (27% vs 14%), and a previous myocardial infarction (9.8% vs 6%).

A Need for Individualized Treatment

Like others, Deepak Bhatt, MD, director of the Mount Sinai Fuster Heart Hospital of the Icahn School of Medicine in New York City, who was invited by ESC to discuss the trial, endorsed the need to individualize antiplatelet strategies following percutaneous interventions. He praised recent efforts, such as the NEO-MINDSET trial, to address unanswered questions about timing, duration, and intensity within specific populations.

In that respect, studies like NEO-MINDSET are important for providing the sorely needed data to guide clinical practice, Bhatt said.

However, he took issue with the language used to describe the NEO-MINDSET result, noting that the paper dubs discontinuation of aspirin as “not noninferior” in this patient population. Bhatt said this language is unclear and suggested that the term “inferior” suffices.

Given the growing strength of the evidence that the benefit-to-risk ratio of antiplatelet therapy following myocardial infarction differs markedly by the variables that increase risk for recurrent thrombosis or bleeding, Bhatt believes that risk scoring strategies will be used increasingly. Rather than “eyeballing” risk factors, he called for an objective approach to match patients to an antiplatelet strategy with an optimal projected balance of benefit to risk.

Tarantini reported having financial relationships with Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Medtronic, but the study he presented received no funding from industry. Lemos reported having financial relationships with Abbott Vascular, Boston Scientific, Braun Melsungen, Daiichi Sankyo, Edwards Lifesciences, and Novo Nordisk, but the study he presented received no industry funding. Bhatt reported having financial relationships with more than 50 pharmaceutical companies. Montalescot reported no conflicts of interest.