ACS: Necessary DAPT after PCI may be shorter than currently advised

Switching to monotherapy with ticagrelor after 1 month of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) appeared non-inferior for major adverse cardiac or cerebrovascular events (MACCE) compared with 12-month DAPT with ticagrelor plus aspirin. Moreover, clinically relevant bleeding events were significantly lower in the ticagrelor monotherapy group.

The current ESC Guidelines recommend DAPT with aspirin plus a potent P2Y₁₂ inhibitor over 12 months after ACS and PCI [1]. The current ULTIMATE-DAPT trial (NCT03971500) investigated the consequences of reducing DAPT to ticagrelor monotherapy after 1 event-free month post-PCI on DAPT [2,3]. The 2 primary endpoints, evaluated through 1 year, were non-inferiority in MACCE (i.e. cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, clinically driven target vessel revascularisation) and superiority in bleedings of types 2, 3, or 5 according to the Bleeding Academic Research Consortium (BARC).

The multinational trial randomised 3,400 adults after 30 days with aspirin plus ticagrelor to either continue this regimen or switch to the P2Y₁₂ inhibitor plus placebo over 1 year. The trial cohort had a median age of around 63 years and slightly over 25% were women. “70% of the patients had single vessel disease and about 1.3 lesions were treated per patient,” added Prof. Gregg Stone (Icahn School of Medicine at Mount Sinai, NY, USA).

The primary endpoint of type 2, 3, or 5 BARC bleedings occurred in 2.1% on ticagrelor only and 4.6% on continued DAPT (HR 0.45; 95% CI 0.30–0.66; P<0.0001; see Figure). The rates of MACCE in both treatment groups were low and were not significantly different: on ticagrelor plus aspirin, 3.7% of the participants experienced a MACCE compared with 3.6% in the ticagrelor plus placebo group (HR 0.98; 95% CI 0.69–1.39; P_{non-inferiority}<0.0001). Of note, the upper confidence interval was 1.39 reflecting a relatively low number of events. The P-value was for non-inferiority with a prespecified margin of 5. Statistical significance was not established for all secondary MACCE endpoints.

Figure: Primary endpoint of BARC types 2, 3, or 5 bleeding in the ULTIMATE-DAPT study [2]

Blee

BARC, Bleeding Academic Research Consortium; CI, confidence interval; HR, hazard ratio.

“These results, in concert with prior trials, warrant an update to the guidelines and a change in practice to treat most patients with ACS after PCI with 1 month only on DAPT, followed by conversion to single antiplatelet therapy with a potent P2Y₁₂ inhibitor, with the strongest evidence to date supporting ticagrelor,” Prof. Stone concluded. While de-escalating aspirin has been shown clearly to reduce bleeding, very large trials would be needed to exclude harm in terms of increased ischaemic risk as evidenced by the wide confidence intervals observed in the trial.

1. Byrne RA, et al. Eur Heart J 2023;44(38):3720-3826.
2. Ge Z, et al. Lancet 2024;403(10439):1866–1878.
3. Stone GW, et al. One-month ticagrelor monotherapy after PCI in acute coronary syndromes: principal results from the double-blind, placebo-controlled ULTIMATE-DAPT trial. LB3, Session 406, ACC 2024 Scientific Session, 6–8 April, Atlanta, USA.

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Posted on 16 May 202413 June 2024