Highlights in interventional cardiology

The European Society of Cardiology Congress 2025 was held in Madrid (Spain) at the end of August 2025. It was very exciting in the area of interventional cardiology and especially of anti-thrombotic therapies.

Multiple studies with immediate clinical implication were presented at the European Society of Cardiology Congress 2025 and published simultaneously in major journals. Due to space constraints, we can describe only few trials presented.

The AQUATIC study

The first randomized placebo-controlled trial looking at efficacy and safety of oral anticoagulation (OAC) plus aspirin versus OAC alone in patients at high risk for atherothrombotic events with a history of coronary stent implantation is the AQUATIC study. In the trial the shortest allowed time since coronary stenting was six months.¹

The primary outcomes of the study were cardiovascular death, myocardial infarction, stroke, systemic embolism, any coronary revascularization, or acute limb ischemia. The secondary safety outcome was major bleeding according to the ISTH classification. Patients were defined at high risk for atherothrombotic events if they previously had percutaneous coronary intervention (PCI) for an acute coronary syndrome (ACS) or if they fulfilled any of the following criteria: diabetes mellitus, chronic kidney disease, peripheral artery disease, multivessel coronary disease, complex PCI (e.g. left main trunk PCI, chronic total occlusion PCI, 3 or more lesions treated) or history of stent thrombosis. The indication for OAC was atrial fibrillation in approximately 90% of the patients and direct oral anticoagulants were used in approximately 90% of the patients. The mean age was approximately 72 years and the median interval between PCI and the enrollment was 3 years.

The patient enrollment in the trial was stopped prematurely after inclusion of 872 patients (out of the initially planned 2000 patients) due to an excess of all-cause mortality in one group. This was observed in an interim analysis after a median follow-up of 2,2 years. The primary endpoint occurred more frequently in the aspirin plus OAC group than in the group with OAC alone with an adjusted hazard ratio (aHR) of 1,53 (95%CI: 1,07–2,18; p=0,019). The aspirin plus OAC group demonstrated an excess in major bleeding with an aHR of 3,35 (95%CI: 1,87–6,00; p<0,001). Finally, all-cause mortality was increased in the aspirin plus OAC group with an aHR of 1,72 (95%CI: 1,14–2,58; p=0,010).

In summary the AQUATIC trial showed that adding aspirin to OAC not only increased the bleeding risk but also increased significantly the risk or ischemic events and all-cause mortality. Therefore, patients on chronic OAC at distance of coronary stenting should not receive an antiplatelet agent on top of OAC even if they are at high atherothrombotic risk.

The TARGET-FIRST trial

The TARGET-FIRST trial enrolled patients with acute myocardial infarction treated with PCI who were classified to be at low ischemic risk. Patients who were on dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor and had no ischemic or bleeding event in the first month post PCI were randomized to single antiplatelet therapy (SAPT) with a potent P2Y12 inhibitor or DAPT continuation for 11 additional months, as currently recommended by the guidelines.² The primary point was a combination of ischemic and bleeding events (i.e. all-cause death, myocardial infarction, stent thrombosis, stroke, or type 3 or 5 bleeding according to BARC- scale) 11 months after randomization and tested for its non-inferiority. The secondary endpoint point included type 2, 3 or 5 bleedings according to BARC scale and was tested for its superiority, assuming the non-inferiority goal for the primal endpoint would be achieved.

As wished by the investigators, TARGET-FIRST enrolled patients with very low risk, evenly split between ST elevation myocardial infarction (STEMI) and non-STEMI. Accordingly, 83% had one vessel disease, 77% had one lesion. The median stent use was 1 stent per patient. The vast majority of patients had normal ventricular function. The P2Y12 inhibitor used was in almost 3/4 of the patients ticagrelor, in almost 1/4 of the patients prasugrel and in 5% of the patients clopidogrel. The primary endpoint met the non-inferiority criteria with an event rate of 2,2% in the DAPT arm and an event rate of 2,1% in the SAPT arm. To be noted, the event rate of the primary endpoint was far lower than the one used in the trial to estimate the simple size for power calculation (3,5%). In addition, there was 50% relative risk reduction for bleeding, though major bleeding (type 3 or 5 according to BARC scale) was not differentiated among the groups.

The TARGET-FIRST investigators concluded that in low-risk acute myocardial infarction patients who were treated with PCI and experienced no ischemic or bleeding events during one month with DAPT, P2Y12 inhibitor monotherapy was noninferior to continuing DAPT to prevent ischemic events and it was associated with halving. It was associated with halving the clinically relevant bleeding events. It must be mentioned that the included patients were at extremely low risk (and may therefore not be representative of the patients encountered in daily practice) and the trial may have been underpowered as a result of the lower-than-expected event rate. Therefore, stopping DAPT after one month of PCI in ACS should be reserved for low-ischemic-risk patients who have a high or very high bleeding risk and who have completed one month of DAPT without ischemic or major bleeding event.

The NEO-MINDSET study

The NEO-MINDSET study randomized 3400ACS patients to SAPT with a potent P2Y12 inhibitor (prasugrel or ticagrelor) or conventional DAPT (aspirin plus one of the two potent P2Y12 inhibitors) who underwent successfully PCI within 4 days from admission.³ The primary ischemic endpoint, tested for non-inferiority, was all-cause death, myocardial infarction, stroke, or urgent target vessels revascularization at 12 months. The primary bleeding endpoint, tested for superiority in case of non-inferiority of the ischemic endpoint, consisted of major or clinical relevant non-major bleeding (type 2, 3 or 5 bleeding according to BARC scale). Approximately 2/3 of the patients presented with STEMI, 20% of the patients were at high bleeding risk, and the proportion of ticagrelor/prasugrel was approximately 2/3 vs. 1/3. The primary ischemic outcome did not meet the criteria for non-inferiority with an event rate of 5,5% in the DAPT and 7,0% in the SAPT group. While there was a significant reduction in type 2, 3 or 5 bleeding (according to BARC scale) in the SAPT group (2,0% vs. 4,9% in the DAPT group) this finding was irrelevant. The conclusion is that early after ACS, DAPT should remain the standard of care. Overall, the results of the NEO-MINDSET trial support the 2023 ESC guidelines, which do not recommend discontinuing DAPT within the first month after ACS.

The DanGer Shock

The DanGer Shock study randomized 355 patients to standard of care versus standard of care plus hemodynamic support with micro-axial flow pump (Impella), who had a STEMI and a cardiogenic shock without comatose cardiac arrest. This study first showed a mortality benefit at 6 months with a mechanical assist device in cardiogenic shock.⁴ At the ESC meeting in Madrid the long-term results of DanGer Shock in a follow-up up to 10 years were presented. The mortality benefit associated with micro-axial flow pump persisted at long-term follow-up with a 30% relative risk reduction in mortality. The conclusion is that in selected patients with cardiogenic shock related to ACS and no comatose out-of-hospital cardiac arrest micro-axial flow pump gives a survival benefit on the long term.

The SWEDEPAD 1 & 2 study

The SWEDEPAD studies randomized 2400 patients with chronic limb ischemia (SWEDEPAD1) and 1300 patients with intermittent claudication (SWEDEPAD2) to percutaneous peripheral interventions with Paclitaxel-coated devices versus uncoated devices. The primary endpoints of the studies were major ipsilateral amputation rates (SWEDEPAD1) and the quality of life (SWEDEPAD2).

In SWEDEPAD1 addressing chronic limb ischemia patients the median age of the patients was 77 years. 53% of the patients had diabetes, 3/4 had advanced peripheral arterial disease with tissue loss, 53% had a femoropopliteal intervention, 28% had a infrapopliteal intervention and 24% had a revascularization of both territories.⁵ During a maximum follow up of 5 years, no difference in major ipsilateral amputation rates between uncoated and drug-coated devices was observed. In addition, there was no difference in target vessel reintervention or all-cause mortality.

SWEDEPAD2 enrolled intermittent claudication patients and the median age was 73 years. 34% of the patients had diabetes, 60% of the patients had severe claudication and 96% had femoropopliteal intervention.⁶ The primary endpoint of quality of life did not differ between drug-coated and uncoated devices. No differences in target vessel reintervention were observed and at 7,1 years, there was no difference in all-cause mortality.

Overall, in SWEDEPAD1 and 2 trials the arms with Paclitaxel-coated devices did not reduce the number of amputations due to chronic limb ischemia, did not improve quality of life in intermittent claudication and overall did not reduce the need for reintervention or effected mortality. While the value of drug-coated devices in coronary intervention is undisputed, these results question their value for the percutaneous treatment of lower extremity arterial disease.

Declaration of interest:

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