The European Society of Cardiology (ESC) Congress remains one of the most influential stages for unveiling pivotal cardiovascular research. The 2025 meeting in Madrid, Spain, was no exception, delivering a rich portfolio of late-breaking and hot line clinical trials that specifically addressed interventional cardiology practice. Several studies focused on optimizing antiplatelet therapy following PCI reflecting ongoing debates about the duration and intensity of dual antiplatelet therapy (DAPT). Others explored novel strategies in complex and high-risk patients. Below is a detailed narrative review of the most impactful interventional trials presented.

The Landscape of Antiplatelet Therapy After PCI

Antiplatelet therapy remains the cornerstone of preventing stent thrombosis and recurrent ischemic events post PCI. Yet, balancing ischemic risk against bleeding risk continues to be one of the most pressing clinical dilemmas. The ESC 2025 trials collectively attempted to refine the "sweet spot" between adequate platelet inhibition and acceptable bleeding safety, each tackling the question from a different clinical angle.

The NEO-MINDSET trial directly addressed one of the most controversial questions in contemporary PCI care: Is aspirin needed beyond the first few days after PCI, particularly in acute coronary syndrome (ACS) patients?

In this large-scale, multicenter study, >3,400 patients undergoing PCI for ACS were randomized to two strategies: standard therapy of DAPT plus aspirin plus a P2Y₁₂ inhibitor for 12 months or experimental therapy of aspirin for no more than 4 days post PCI, then continued with P2Y₁₂ inhibitor monotherapy for the remainder of the year.

The results were striking. The early aspirin withdrawal strategy failed to demonstrate noninferiority compared with standard DAPT. The primary ischemic composite (death, myocardial infarction [MI], stroke or urgent revascularization) occurred more frequently in the aspirin-sparing arm, especially within the first 30 days after PCI. While bleeding events were reduced with P2Y₁₂ monotherapy, the early excess in ischemic events raised serious safety concerns.

Clinically, NEO-MINDSET tempers enthusiasm for ultra-short aspirin regimens in high-risk ACS populations. It underscores that while bleeding avoidance is important, the first month post PCI remains the most vulnerable period for thrombotic complications. In practice, this trial suggests clinicians should be cautious about removing aspirin too early outside of select low-risk scenarios.

TAILORED-CHIP evaluated personalizing therapy in complex high-risk PCI (CHIP) – patients who represent a particularly challenging subgroup. These individuals often have diffuse multivessel disease, left main involvement, chronic total occlusions or significant comorbidities such as diabetes and renal impairment.

TAILORED-CHIP examined whether a tailored escalation/de-escalation approach could improve outcomes in this population. The experimental arm received intensified therapy with ticagrelor plus aspirin for six months, followed by de-escalation to clopidogrel monotherapy. The control arm received standard 12 months of DAPT with aspirin plus clopidogrel.

Disappointingly, the tailored strategy did not improve ischemic outcomes. Rates of death, MI and stent thrombosis were similar between groups. Moreover, the escalated regimen led to a significant increase in bleeding events compared with standard DAPT.

The message from TAILORED-CHIP is clear: in complex PCI patients, adding pharmacologic intensity does not necessarily translate into ischemic protection, but it does increase bleeding risk. Standard DAPT, rather than complicated escalation/de-escalation strategies, remains the safer choice until further evidence emerges.

TARGET-FIRST looked at aspirin withdrawal after one month of DAPT. While NEO-MINDSET showed that removing aspirin too early is unsafe, the TARGET-FIRST trial asked a related but slightly different question: Can aspirin be safely withdrawn after one month of uneventful DAPT?

This trial enrolled patients with acute MI who underwent successful complete revascularization with contemporary drug-eluting stents. After one month of DAPT without events, patients were randomized either to continue DAPT for a full year or to switch to P2Y₁₂ inhibitor monotherapy for the remaining 11 months.

Here, the results were more favorable for aspirin withdrawal. The monotherapy arm was noninferior to standard DAPT for ischemic events and demonstrated significantly lower rates of clinically relevant bleeding.

TARGET-FIRST builds on previous work such as TWILIGHT and GLOBAL LEADERS, adding clarity to the timing of aspirin withdrawal. Together, the evidence suggests that in lower-risk patients with early complete revascularization and no early events, one month of DAPT may be sufficient before transitioning to monotherapy. This could reshape practice guidelines by supporting shorter DAPT durations in carefully selected populations.

DAPT-SHOCK-AMI, a trial of antiplatelet strategies in cardiogenic shock, was one of the first randomized efforts to address antiplatelet therapy in the setting of acute MI complicated by cardiogenic shock (CS) – a group notoriously excluded from most prior studies.

The trial compared intravenous cangrelor (bolus plus infusion, followed by maintenance oral therapy) against crushed oral ticagrelor loading in patients undergoing primary PCI in shock. Pharmacodynamic testing confirmed what many suspected: cangrelor achieved much faster and more consistent platelet inhibition than crushed ticagrelor, a clear advantage in a setting where rapid efficacy is paramount.

However, when it came to clinical outcomes, cangrelor did not meet noninferiority for the composite of death, MI or stroke at 30 days. Mortality and ischemic event rates remained high in both groups, reflecting the severity of this patient population. Bleeding rates were similar between arms.

Although underpowered for definitive clinical conclusions, DAPT-SHOCK-AMI highlights the complexity of managing antiplatelet therapy in CS. Intravenous strategies like cangrelor may offer pharmacodynamic advantages, but whether this translates into survival benefit requires larger, outcome-focused trials.

The DanGer Shock trial was the first randomized controlled study to show that routine use of the Impella CP microaxial flow pump can improve survival in patients with STEMI complicated by cardiogenic shock. In this multicenter trial of 355 patients across Denmark, Germany and the UK, those randomized to Impella support plus standard care had significantly lower six-month mortality compared with standard care alone (46% vs. 59%). While Impella improved hemodynamics and lactate clearance, it came at the cost of higher rates of bleeding, renal injury and vascular complications.

At ESC 2025, the 10-year follow-up results were presented, showing a durable survival advantage: mortality was 53% in the Impella arm vs. 69% in controls, corresponding to a 16% absolute reduction and an average of about 600 more days alive. The benefit appeared strongest in patients presenting with lower systolic blood pressure, highlighting the importance of early device deployment in those with the most profound shock. Taken together, DanGer Shock provides the first long-term evidence that early Impella support not only stabilizes patients acutely but also translates into sustained survival benefit, marking a pivotal step in the management of infarct-related cardiogenic shock.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Cardiology Magazine, ACC Publications, ESC Congress, ESC25, Percutaneous Coronary Intervention, Myocardial Infarction, Dual Anti-Platelet Therapy