Hot Line 7: NEO-MINDSET, TAILORED-CHIP, TARGET-FIRST and DAPT-SHOCK-AMI
31 Aug 2025
Hot Line ESC Congress 2025 Different approaches to optimise antiplatelet therapy after a myocardial infarction (MI) were discussed in Hot Line 7.
Firstly, Professor Pedro Lemos (Hospital Israelita Albert Einstein - Sao Paulo, Brazil) explained that the NEO-MINDSET trial randomised 3,410 patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) with drug-eluting stents to either P2Y12 inhibitor monotherapy or dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) for 12 months. The first primary outcome – death, MI, stroke or urgent target-vessel coronary revascularisation – occurred in 7.0% of patients in the monotherapy group and 5.5% in the DAPT group (hazard ratio [HR] 1.28; 95% CI 0.98 to 1.68), resulting in an absolute risk difference of +1.47 percentage points (95% CI –0.16 to 3.10), which did not meet the prespecified criteria for noninferiority (p=0.11). Major or clinically relevant nonmajor bleeding occurred in 2.0% with monotherapy and 4.9% with DAPT. Prof. Lemos highlighted that the results of a landmark analysis indicated that the excess ischaemic risk with monotherapy occurred in the first 30 days, with comparable outcomes thereafter, while bleeding appeared to be lower at both 30 days and 12 months with monotherapy vs. DAPT.
An alternative to standard DAPT was tested in patients with high-risk anatomical or clinical characteristics undergoing complex PCI in the TAILORED-CHIP trial. Presented by Professor Duk-Woo Park (Asan Medical Center - Seoul, South Korea), early escalation with low-dose ticagrelor plus aspirin and late de-escalation with clopidogrel alone was compared with standard DAPT. The primary outcome of all-cause death, MI, stroke, stent thrombosis, unplanned urgent revascularisation and clinically relevant bleeding was not significantly different, occurring in 10.5% of patients on tailored antiplatelet therapy and 8.8% on standard DAPT (HR 1.19; 95% CI 0.90 to 1.58; p=0.21) at 12 months. However, clinically relevant bleeding at 12 months was significantly higher with tailored therapy than DAPT (7.2% vs. 4.8%; p=0.002). Professor Park concluded: “We observed an increase in bleeding complications without a significant reduction in ischaemic events. This challenges the notion that ‘more is better’ even in carefully selected patients at high ischaemic risk undergoing complex PCI procedures. Standard 12-month DAPT remains appropriate.”
Professor Giuseppe Tarantini (University of Padua - Padua, Italy) explained the rationale of the TARGET-FIRST trial: “No randomised trials have previously assessed early aspirin discontinuation in acute MI patients who achieve early, complete revascularisation with modern stents. In such cases, bleeding risk may outweigh residual ischaemic risk, making antiplatelet therapy de-escalation attractive.” In total, 1,942 patients who completed 1 month of DAPT without adverse events were randomised to continue DAPT or switch to P2Y12 inhibitor monotherapy for 11 months. For the primary endpoint – all-cause death, MI, stent thrombosis, stroke or BARC type 3/5 bleeding – monotherapy was noninferior to DAPT (2.10% vs. 2.18%; difference –0.09 percentage points; 95% CI –1.39 to 1.20; p=0.021 for noninferiority). Furthermore, the main secondary endpoint (BARC type 2/3/5 bleeding) was significantly lower with monotherapy (2.65% vs. 5.57%; HR 0.46; 95% CI 0.29 to 0.75; p=0.002). Professor Tarantini concluded: “These results reflect the benefits of modern stents, high procedural success and optimal medical therapy, making early aspirin discontinuation feasible in this selected population.”
To end, Professor Zuzana Motovska (Charles University and University Hospital Kralovske Vinohrady - Prague, Czechia) described the DAPT-SHOCK-AMI trial: “This is the first-ever randomised study of antiplatelet drugs in the cardiogenic shock population with acute MI in the 30 years since these drugs have been recommended.” More than 600 patients were randomised to receive IV cangrelor (IV bolus of 30 μg/kg followed by a continuous infusion at 4 μg/kg) or oral ticagrelor (crushed tablets at a 180-mg loading dose and then a maintenance dose of 90 mg twice daily). The primary laboratory endpoint (defined as platelet reactivity index <50% at the end of primary angioplasty) was achieved in 100% of patients with cangrelor and in 22.1% with ticagrelor (p for superiority<0.0001). At 30 days, the primary clinical endpoint was not met: 37.6% of patients in the cangrelor group and 41.0% of patients in the ticagrelor group experienced all-cause death, MI or stroke (difference –3.5%; 95% CI –11.2% to 4.3%; p for noninferiority=0.13). The incidence of all-cause mortality at 12 months was 43.6% in the cangrelor group and 49.2% in the ticagrelor group, while the incidence of major bleeding at 30 days was 6.4% and 5.2%, respectively. Professor Deepak Bhatt (Icahn School of Medicine at Mount Sinai - New York, USA), concluded: “Compared with crushed ticagrelor, IV cangrelor provided immediate, effective platelet inhibition and improved several secondary and exploratory clinical outcomes without increasing major bleeding. If verified in larger trials, IV cangrelor could represent a major advancement in the treatment of cardiogenic shock.”
