Ultra-Thin Sirolimus-Eluting Stents Show Noninferiority to Everolimus-Eluting Stents in Diabetic Multivessel CAD: Insights from TUXEDO-2 Trial

Highlight

The TUXEDO-2 trial compared ultra-thin biodegradable polymer sirolimus-eluting stents (BP-SES) with durable polymer everolimus-eluting stents (DP-EES) in diabetic patients with multivessel coronary artery disease (CAD). At 1 year, BP-SES demonstrated noninferior target lesion failure rates compared to DP-EES. Safety endpoints, including cardiac death, myocardial infarction, and stent thrombosis, were comparable between the stent groups.

Study Background

Patients with diabetes mellitus undergoing percutaneous coronary intervention (PCI) for multivessel coronary artery disease represent a challenging cohort due to diffuse atherosclerosis and a heightened risk of adverse cardiovascular events, including restenosis, stent thrombosis, and myocardial infarction. Drug-eluting stents (DES) have evolved to address these challenges by combining pharmacologic agents and stent platform design to reduce neointimal hyperplasia and improve long-term vessel patency. However, many stent comparison trials have excluded diabetic patients or enrolled them in limited numbers, leaving a gap in evidence regarding optimal stent selection in this high-risk group.

New-generation ultra-thin strut DES with biodegradable polymers, such as the sirolimus-eluting Supraflex Cruz stent, have been developed with the intent to enhance vascular healing and reduce polymer-induced inflammation, theoretically benefiting diabetic patients prone to impaired endothelial function. Conversely, durable polymer everolimus-eluting stents like Xience have established long-term safety and efficacy but may have limitations due to persistent polymer presence. This trial aimed to directly compare these two modern DES platforms in diabetic patients undergoing multivessel PCI to guide clinical decision-making.

Study Design

The TUXEDO-2 study was a prospective, investigator-initiated, multicenter, open-label, randomized controlled trial with a 2 × 2 factorial design. A total of 1,800 patients with diabetes and angiographically confirmed multivessel coronary artery disease undergoing PCI were enrolled and randomized 1:1 to receive either the ultra-thin strut biodegradable polymer Supraflex Cruz sirolimus-eluting stent (BP-SES) or the established durable polymer Xience everolimus-eluting stent (DP-EES). Additionally, patients were randomized to dual antiplatelet therapy with either ticagrelor or prasugrel, reflecting contemporary optimal medical therapy.

The primary endpoint was target lesion failure (TLF) at 1 year, defined as a composite of cardiac death, target vessel myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR). The trial was designed to test noninferiority of BP-SES compared with DP-EES with a prespecified noninferiority margin of 4.5% and a one-sided 97.5% confidence interval boundary.

Key Findings

At 1-year follow-up, target lesion failure occurred in 7.92% of patients in the BP-SES group versus 8.75% in the DP-EES group (risk difference -0.83 percentage points; one-sided upper 97.5% confidence bound 3.42%). This met the pre-specified noninferiority criterion (p for noninferiority = 0.005), indicating comparable efficacy between the two stent platforms.

Analyzing components of the primary endpoint, cardiac death occurred in 3.6% of the BP-SES group and 3.4% of the DP-EES group. Target vessel MI rates were 6.61% and 7.54%, respectively, without statistically significant differences. Ischemia-driven TLR rates were low and similar (0.8% vs. 1.0%). Other safety outcomes such as nonfatal MI (4.7% BP-SES vs 6.4% DP-EES) and stent thrombosis (1.0% vs 0.7%) were also comparable, supporting the safety profile of the ultra-thin biodegradable polymer stent in this high-risk population.

These results are clinically important given the complexity of diabetic multivessel disease and the historical challenges in achieving optimal PCI outcomes. The noninferiority finding suggests that ultra-thin strut BP-SES can be a suitable alternative to the well-established DP-EES, potentially offering benefits related to polymer biodegradability and minimized vessel injury associated with thinner struts.

Expert Commentary

Diabetic coronary artery disease presents a unique challenge due to more diffuse and accelerated atherosclerosis, endothelial dysfunction, and higher rates of restenosis and late stent thrombosis. The TUXEDO-2 study addresses an important gap by evaluating newer stent technology designed to mitigate these risks.

The ultra-thin strut design of the Supraflex Cruz stent may enhance endothelial recovery and reduce flow disturbance, which, combined with a biodegradable polymer, could theoretically reduce chronic inflammatory responses. Although this trial’s results indicated noninferiority rather than superiority, the comparable safety and efficacy outcomes support the broader adoption of BP-SES in diabetic multivessel PCI settings.

Limitations of the study include its open-label design and the relatively short 1-year follow-up period; longer-term data are warranted to assess very late events such as stent thrombosis or neoatherosclerosis. Moreover, while the trial randomized antiplatelet therapy allowing real-world applicability, subgroup analyses on medication interactions would help optimize tailoring therapy further.

Conclusion

The TUXEDO-2 trial provides compelling evidence that in patients with diabetes and multivessel coronary artery disease undergoing PCI, ultra-thin strut biodegradable polymer sirolimus-eluting stents are noninferior to durable polymer everolimus-eluting stents at 1-year follow-up. This finding supports the use of newer-generation ultra-thin BP-SES as a safe and effective alternative in this challenging patient population. Future studies with extended follow-up and larger cohorts could elucidate potential long-term benefits and refine stent and pharmacotherapy selection in diabetic CAD management.

Funding and Trial Registration

The trial was registered under CTRI/2019/11/022088. Funding sources were not explicitly detailed in the available publication information.

References

Kaul U, Sinha SK, Singh R, et al. Ultra-Thin Sirolimus-Eluting Versus Everolimus-Eluting Stents in Diabetic Multivessel Coronary Artery Disease Patients: The TUXEDO-2 Trial. J Am Coll Cardiol. 2026 Jun 24. PMID: 42383943.