Key Points:
- The optimal time to de-escalate from DAPT to SAPT following PCI with modern DES after ACS is uncertain.
- The ULTIMATE-DAPT study found that transitioning from aspirin and ticagrelor to ticagrelor alone after 1 month was superior for bleeding outcomes and non-inferior for ischemic outcomes at 12 months compared to continuous DAPT for 12 months.
Current guidelines recommend dual anti-platelet therapy (DAPT) with aspirin plus a potent P2Y12 receptor inhibitor for 12 months for most patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) in order to prevent recurrent myocardial infarction (MI) or in-stent thrombosis (IST). However, de-escalation from DAPT to single antiplatelet therapy (SAPT) earlier in post-ACS patients who receive a drug-eluding stent (DES) may reduce bleeding without affecting ischemic risk, thus conferring a net benefit.
On April 7, 2024, the principal results of the “Ticagrelor Alone Versus Ticagrelor Plus Aspirin from Month 1 to Month 12 After PCI in Patients with ACS (ULTIMATE-DAPT)” were presented at ACC Scientific Sessions 2024 as a Late Breaking Clinical Trial with simultaneous publication in Lancet. The purpose of this trial was to determine whether SAPT with ticagrelor alone starting 30 days post-PCI for ACS reduced bleeding without increasing major adverse cardiovascular or cerebrovascular events (MACCE) compared to continuation of ticagrelor plus aspirin through 12 months.
This multicenter, international, double-blind, placebo-controlled trial randomized adults who received intravascular ultrasound-guided PCI for ACS with DES and remained event free at 1 month on ticagrelor 90mg twice a day plus aspirin 100mg once a day in a 1:1 fashion to the intervention arm of ticagrelor alone plus placebo or control arm of ticagrelor plus aspirin 100mg daily. Patients with recent stroke, prior coronary bypass grafting, significant kidney dysfunction (eGFR < 20 ml/min/1.73 m2), or need for chronic anticoagulation were excluded. The primary effectiveness endpoint was clinically-relevant bleeding, powered for superiority, and the primary safety endpoint was composite MACCE (cardiac death, MI, IST, target vessel revascularization), powered for non-inferiority.
Overall, 3400 patients were randomized; only 1 was lost to follow up. Median age was 62 years, about 75% were male, nearly 90% were Chinese race, and 30% were smokers. Nearly 90% underwent complete revascularization. Adherence to assigned treatment was >98% in both arms.
For the primary effectiveness endpoint, patients randomized to ticagrelor monotherapy at one month had a significantly lower rate of clinically significant bleeding at 12 months compared to those randomized to continuous DAPT (HR 0.45 [95% CI 0.30-0.66]). For the primary safety endpoint of MACCE, the ticagrelor monotherapy was non-inferior to continuous DAPT arm with an absolute difference of 0.1% at the end of the study period (HR 0.98 [95% CI 0.69-1.39], p <0.0001 for non-inferiority, p=0.89 for superiority). There were no significant interactions for any of the 12 prespecified subgroups for either endpoint. As the vast majority of patient were from China, generalizability to other populations may be limited.
Dr. Gregg Stone of Icahn School of Medicine at Mount Sinai concluded: “In treating a broad range of patients with acute coronary syndromes in the era of contemporary drug eluting stents, among those who were stable after one month of DAPT, continuing treatment with ticagrelor alone reduced bleeding with no increase in adverse ischemic thrombotic events… These data suggest that a 12-month duration of DAPT is not only not necessary in most patients with ACS but is harmful.”