Ultrathin-strut Biodegradable Polymer Sirolimus-eluting Stents With P2Y12 Inhibitor-based Single Antiplatelet Therapy vs. Conventional DAPT for Unprotected Left Main Coronary Artery Disease (ULTIMATE-LM)

Summary

The management of patients with unprotected left main coronary artery (LMCA) disease undergoing percutaneous coronary intervention (PCI) in contemporary interventional cardiology practice remains matter of intense debate. Particularly, the combination of the optimal drug-eluting stent (DES) selection and antiplatelet regimen for patients who require LMCA PCI remains undetermined.

Newer-generation drug-eluting stents with ultrathin-strut metallic platforms have been shown to reduce the risk of target lesion failure compared with thicker-strut drug-eluting stents among all-comer patients undergoing PCI, a difference mainly driven by a lower risk of ischemia-driven target lesion revascularization. In the TALENT prospective, single-blind, multicenter, randomized controlled trial that included 1'435 all-comer patients undergoing PCI, the Supraflex ultrathin-strut biodegradable polymer sirolimus-eluting stent was found non-inferior to the Xience® thin-strut permanent polymer everolimus-eluting stent (Abbott Vascular, USA) with regards to the device-oriented composite clinical endpoint (DoCE), a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization, at 12 months of follow-up. However, the TALENT trial included only 31 (1.5%) lesions located in the left main coronary artery. In the COMPARE 60/80 HBR investigator-initiated, multicenter, prospective randomized trial which included a total of 732 patients at high-bleeding risk undergoing PCI with the Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent or the Ultimaster Tansei (Terumo Corp., Tokyo, Japan), the rates of the primary endpoint of the net adverse clinical endpoint, defined as a composite of cardiac death, myocardial infarction, target vessel revascularization, stroke, or BARC 3 or 5 major bleeding events at 12 months were similar in the Supraflex Cruz and the Ultimaster Tansei groups, meeting the prespecified criterion for non-inferiority of the Supraflex Cruz DES compared to the Ultimaster Tansei DES. The safety and efficacy of the Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent combined with potent P2Y12 inhibitor aspirin-free SAPT among all-comer patients undergoing PCI for complex coronary lesions, such as patients with LMCA stenosis, have however not been investigated to date.

Recent evidence from a large-scale meta-analysis of several randomized clinical trials including \>32'000 patients indicated that 1-3 months of DAPT followed by P2Y12 inhibitor single antiplatelet therapy (SAPT) after second-generation DES implantation was associated with lower risk for major bleeding and similar risk for adverse ischemic outcomes compared with conventional DAPT. These findings suggest that P2Y12 inhibitor SAPT following a short DAPT course (1-3 months) may represent a valuable treatment option for patients undergoing PCI with newer-generation DES compared to standard conventional 12 months DAPT, but this strategy has never been investigated in dedicated randomized clinical trials focused on patients at highest-risk for ischaemic events, such as patients undergoing LMCA PCI.

The ULTIMATE-LM randomized trial aims at filling this current gap of knowledge, which may have large impact on clinical practice and international guidelines. ULTIMATE-LM will be the first randomized clinical trial to investigate the safety and efficacy of a novel ultrathin-strut biodegradable polymer drug-eluting stent (Supraflex Cruz, Sahajanand Medical Technologies Ltd., Surat, India)) combined with P2Y12 inhibitor-based single antiplatelet therapy among patients undergoing PCI for LMCA disease.

Conditions

• Left Main Coronary Artery Stenosis

Interventions

DEVICE

LMCA PCI with Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India).

Successful LMCA PCI with ≥1 Supraflex Cruz ultrathin-strut biodegradable polymer sirolimus-eluting stent (Sahajanand Medical Technologies Ltd., Surat, India).

DRUG

P2Y12 inhibitor-based SAPT after short DAPT

Potent P2Y12 inhibitor-based SAPT (ticagrelor 90 mg bd, or prasugrel 5 or 10 mg od, at the discretion of the investigator) during 2 years. Aspirin stopped after LMCA or at latest at hospital discharge.

DRUG

Conventional DAPT

6 to 12 months of DAPT combining aspirin (≥75 mg od) and a P2Y12 inhibitor (clopidogrel 75 mg od, ticagrelor 90 mg bd, prasugrel 5 or 10 mg od at the discretion of the investigator) followed by aspirin SAPT.

Sponsors & Collaborators

• University of Bern

  collaborator OTHER

• IGLESIAS Juan Fernando

  lead OTHER

Principal Investigators

• Juan F. Iglesias, MD · Geneva University Hospitals, Switzerland

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-26

Primary Completion

2028-05-01

Completion

2032-05-01

Countries

• Switzerland

Study Locations