Comparison of 1-month vs. 12-month dual antiplatelet therapy after implantation of drug-eluting stents in patients with acute coronary syndrome: the ULTIMATE-DAPT trial

Abstract

The 2023 ESC guidelines assigned to 12-month dual antiplatelet therapy (DAPT) the single class I recommendation on DAPT in patients with acute coronary syndrome (ACS) after drug-eluting stent (DES) im-plantation. However, evidence exists that various DAPT de-escalation strategies are preferable to 12-month DAPT, which has sparked ongoing debate. 1,2 Several randomized clinical trials (RCTs) and individual patient data (IPD) meta-analysis investigated the efficacy and safety of P2Y 12 inhibitor monotherapy after 1-3 months of DAPT. The GLOBAL LEADERS trial, encompassing all-comer patients, found no clear superiority on death or Q-wave myocardial infarction (MI) between a 1-month DAPT followed by ticagrelor monotherapy and standard 12-month DAPT followed by aspirin after DES implant-ation. The bleeding risk was reduced in ACS (1.95% vs. 2.68%) but not chronic coronary syndrome patients (2.13% vs. 1.62%) with 1-month DAPT, 3,4 which contributed to foster additional research efforts with P2Y 12 inhibitor monotherapy. The GLOBAL LEADERS Adjudication Sub-StudY (GLASSY), which, unlike the parent trial, implemented a central adjudication of events, confirmed the potential of lower bleeding and similar fatal or non-fatal ischaemic risks with ticagrelor monotherapy than standard DAPT. 5 The TWILIGHT study, which included selected high-risk patients including ACS, showed that after 3 months of DAPT, ticagrelor monother-apy was safer [Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding 1% vs. 2%] and similarly effective [major adverse cardiovascular events (MACE) endpoint: a composite of all-cause death, non-fatal MI, or non-fatal stroke; P for non-inferiority <0.001] compared with standard additional 12-month DAPT. 6 The SIDNEY-2 Collaboration, involving over 38,000 patients, supported P2Y 12 inhibitor monotherapy for reducing BARC type 3 or 5 bleeding events by 44% [hazard ratio (HR) 0.56; 95% confidence interval (CI): 0.41-0.75] and demonstrated its non-inferiority for MACE compared to standard DAPT, with notable benefits for bleeding in ACS patients (P for interaction 0.51) 7 and those undergoing complex percutaneous coronary intervention (PCI). 8 While these findings hold true for ticagrelor in ACS patients in a more recent IPD analysis, they may not be applicable when clopidogrel is used. 9 Trial description The ULTIMATE-DAPT trial was designed to test whether antiplatelet monotherapy with ticagrelor alone vs. ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients following DES who have completed a 1-month course of DAPT with aspirin plus ticagrelor. The ULTIMATE-DAPT was a prospective, multicentre, randomized, controlled trial. Patients were initially randomized to intravascular ultrasound (IVUS)-guided (n = 1753) or angiography-guided (n = 1752) PCI for index ACS event and received DAPT with ticagrelor (90 mg b.i.d.) and aspirin (100 mg q.d.) for 30 days. If they had no ischaemic or bleeding events at the end of 30 days, they were randomized to continuing DAPT for 12 months total (n = 1700) or stopping aspirin and switching to tica-grelor + placebo (n = 1700). 10 Patient population In total, 3400 patients were randomized. Their median age was 63, 26% of the patients were females, 31.6% had diabetes, and 7% had chronic kidney disease (CKD), whereas severe CKD was an exclusion criterion, together with chronic oral anticoagulation, stroke within 3 months or any permanent neurologic deficit, and prior intracranial bleed, previous coronary artery bypass graft (CABG), or any planned surgery within 90 days. Overall, 40% of patients had unstable angina, European Heart Journal: Acute Cardiovascular Care (2024) 13, 368-369 https://doi.