Early withdrawal of aspirin following successful PCI for acute coronary syndrome and in low-risk patients following an acute myocardial infarction (MI) was the focus of two separate hot line trials presented at ESC Congress 2025. A third trial provided insights into early escalation and late de-escalation of antiplatelet therapy after complex PCI.

In the NEO-MINDSET trial, simultaneously published in NEJM, researchers in Brazil randomized approximately 3,400 patients within the first four days of hospitalization following a successful PCI to either stop treatment with aspirin and receive potent P2Y12 inhibitor monotherapy (ticagrelor or prasugrel) or to receive dual antiplatelet therapy (DAPT) that included aspirin and a potent P2Y12 inhibitor for 12 months.

At 12 months, the primary endpoint of death from any cause, MI, stroke or urgent revascularization had occurred in 119 patients in the monotherapy group and in 93 patients in the DAPT group (p=0.11 for noninferiority). Researchers also noted that major or clinically relevant nonmajor bleeding occurred in 33 patients assigned to monotherapy vs. 82 patients assigned to DAPT. Stent thrombosis occurred in 12 patients in the monotherapy group and in 4 in the dual antiplatelet therapy group.

"We failed to demonstrate the noninferiority of aspirin-free monotherapy initiated immediately after PCI with regard to the ischemic primary endpoint over 12 months," said Principal Investigator Pedro Lemos, MD. "Results from the landmark analysis suggest that the excess ischemic risk with monotherapy occurred in the first 30 days, with comparable outcomes thereafter. Bleeding appeared to be lower at both 30 days and 12 months with monotherapy vs. DAPT."

In TARGET-FIRST, also simultaneously published in NEJM, P2Y12-inhibitor monotherapy was noninferior to continued DAPT with respect to the occurrence of adverse cardiovascular and cerebrovascular events among low-risk patients with acute MI who had undergone early complete revascularization and had completed one month of DAPT without complications. It also resulted in lower incidence of bleeding events.

Nearly 2,000 patients from 40 centers in Europe were randomized to receive P2Y12-inhibitor monotherapy or to continue DAPT for 11 months. A primary-outcome event occurred in 20 patients (2.1%) in the P2Y12-inhibitor monotherapy group and in 21 patients (2.2%) in the dual antiplatelet therapy group (p=0.02 for noninferiority). Major bleeding occurred in 2.6% of the patients assigned to P2Y12-inhibitor monotherapy group compared with 5.6% of those assigned to DAPT (p=0.002 for superiority). The incidence of stent thrombosis and serious adverse events appeared to be similar in the two groups, researchers said.

Principal Investigator Giuseppe Tarantini, MD, noted that no previous randomized trials have assessed early aspirin discontinuation in acute MI patients who achieve early, complete revascularization with modern stents. "These results reflect the benefits of modern stents, high procedural success and optimal medical therapy, making early aspirin discontinuation feasible in this selected population," he said.

The TAILORED-CHIP trial found early escalation and late de-escalation of antiplatelet therapy is not beneficial in patients with high-risk anatomical or clinical characteristics undergoing complex PCI.

Researchers in South Korea randomized approximately 2,000 patients to standard DAPT (clopidogrel plus aspirin for 12 months) or a tailored antiplatelet strategy consisting of early escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin for 6 months) followed by late de-escalation (clopidogrel monotherapy for 6 months).

Overall findings showed no significant difference in the incidence of major ischemic events at 12 months with tailored therapy compared with standard DAPT. However, the incidence of clinically relevant bleeding was significantly higher with tailored therapy, according to study investigators.

"Our results suggest that a tailored strategy in patients undergoing complex high-risk PCI does not provide a net clinical benefit," said Principal Investigator Duk-Woo Park, MD, PhD, FACC. "We observed an increase in bleeding complications without a significant reduction in ischemic events. This challenges the notion that 'more is better' even in carefully selected patients at high ischemic risk."