DAPT can be safely de-escalated to ticagrelor monotherapy after PCI with stent

This summary is based on the presentation of Marco Valgimigli, MD, PhD (Lugano, Switzerland) at the ESC Congress 2024 - Ticagrelor monotherapy or DAPT after drug-eluting coronary stenting in patients with or without acute coronary syndrome: a patient-level meta-analysis of randomized controlled trials.

Introduction and methods

According to the 2023 ESC Guidelines for the management of ACS, the standard treatment for patients with ACS is dual antiplatelet therapy (DAPT) for 12 months. Depending on the patient’s bleeding risk, it is possible to shorten the duration of DAPT and continue treatment with a P2Y₁₂ inhibitor or aspirin only. Recent studies have shown the efficacy of abbreviated DAPT versus the standard DAPT regimen depends on the drug used as monotherapy.

In a systematic review and individual patient-level meta-analysis, 6 RCTs (2 double-blind and 4 open-label studies) with blinded central outcome adjudication that compared the efficacy and safety of ticagrelor monotherapy (90 mg twice daily) after short-term DAPT (ranging from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing PCI with coronary drug-eluting stent implantation (total n=24,407) were included. Of these patients, 18,135 (74.3%) had ACS, mainly NSTEMI. In the abbreviated DAPT group, the median duration of DAPT after PCI before de-escalation to ticagrelor monotherapy was 78 days (IQR: 31–92).

The 3 hierarchical coprimary endpoints were: (1) major adverse cardiovascular and cerebrovascular events (MACCE), a composite outcome of all-cause mortality, MI, or stroke; (2) major bleeding, defined as Bleeding Academic Research Consortium score 3 or 5; and (3) all-cause mortality. The first endpoint was tested for noninferiority in the per-protocol population (with a prespecified noninferiority margin of 1.15 for the HR), whereas the other 2 endpoints were tested for superiority in the intention-to-treat population.

Main results

• In the per-protocol population (n=23,256), MACCE occurred in 297 patients assigned to ticagrelor monotherapy (Kaplan–Meier estimate: 2.8%) and 332 patients receiving DAPT (Kaplan–Meier estimate: 3.2%) (HR: 0.91; 95%CI: 0.78–1.07; P=0.0039 for noninferiority), with a negligible degree of heterogeneity (I²=0.0%; τ²<0.0001).
• In the intention-to-treat population (n=24,407), ticagrelor monotherapy reduced the risk of major bleeding compared with DAPT (Kaplan–Meier estimate: 0.9% vs. 2.1%; HR: 0.43; 95%CI: 0.34–0.54; P<0.0001 for superiority; heterogeneity: I²=40.9%; τ²=0.079), as well as the risk of all-cause mortality (Kaplan–Meier estimate: 0.9% vs 1.2%; HR: 0.76; 95%CI: 0.59–0.98; P=0.034 for superiority; heterogeneity: I²=0.0%; τ²<0.0001).
• Among ACS patients, comparable results were found for ticagrelor monotherapy versus DAPT (HR for MACCE: 0.89; 95%CI: 0.74–1.06; HR for major bleeding: 0.34; 95%CI: 0.26–0.45; HR for all-cause mortality: 0.74; 95%CI: 0.55–0.99).
• A prespecified trial sequential analysis showed strong evidence for noninferiority of ticagrelor monotherapy for MACCE and superiority for major bleeding but inconclusive evidence for superiority of ticagrelor monotherapy for all-cause mortality, both in the total study population and ACS patients.
• Subgroup analysis in the intention-to-treat population demonstrated the treatment effects of ticagrelor monotherapy versus DAPT on MACCE and all-cause mortality were greater in women than men (both P for interaction≤0.050).

Conclusion

In this systematic review and meta-analysis among patients undergoing PCI with coronary drug-eluting stent implantation, de-escalation to ticagrelor monotherapy after short-term DAPT reduced the risks of major bleeding and all-cause mortality compared with 12-month DAPT, without increasing ischemic risk. These results were confirmed in patients with ACS.

- Our reporting is based on the information provided at the ESC Congress 2024 and the publication of the data in The Lancet -

The findings of this study were simultaneously published in The Lancet.