State-of-the-art practice in 3VD CAD combining predictive score, contemporary CTO expertise, angiography-derived physiology, intravascular Imaging and P2Y12 mono therapy: The Multivessel TALENT

Abstract Background Clinical outcomes after PCI for three-vessel disease (3VD) have improved with best-practice strategies exemplified by the SYNTAX II trial. The Supraflex Cruz SES, featuring a long valley-to-valley Z-connector, provides enhanced flexibility and pushability and may compete with the current best-in-class stents in complex lesions. Purpose We aimed to demonstrate the noninferiority of the Supraflex Cruz SES versus SYNERGY EES with patient oriented composite endpoint (POCE) with 3VD undergoing State-of-the-art PCI. Methods The Multivessel TALENT trial is a prospective, multicentre (54 centres across Europe), open-label, randomized controlled study comparing the clinical outcomes of PCI with Supraflex Cruz stents versus SYNERGY stents in patients with de novo 3VD without left main involvement. State-of-the-art PCI was applied to all patients, encompassing Heart Team decision-making guided by the SYNTAX Score II, functional assessment using quantitative flow ratio (QFR) by an independent corelab, stent optimization with IVUS/OCT, and prasugrel monotherapy following one month of dual antiplatelet therapy (DAPT). The primary endpoint was the one-year POCE, defined as all-cause death, any stroke, any myocardial infarction, or any revascularisation assessed in a non-inferiority statistical scheme. Results Between September 22, 2020, and September 26, 2024, a total of 1,548 patients were randomly assigned to treatment (774 in each group). At 12 months, the primary endpoint occurred in 117 patients (15.3%) in the Supraflex Cruz group and in 111 patients (14.6%) in the SYNERGY group (absolute difference −0.73% one-sided 95% upper confidence bound 3.73%; p for non-inferiority 0.026)(Figure 1A and B). The assumed event rate was 10.7% in each group; however, the observed rate was higher than expected, primarily driven by a greater number of periprocedural myocardial infarctions adjudicated according to the SCAI criteria. Based on the observed event rate of 14.6%, the corresponding non-inferiority margin was 5.83%, yielding a p-value for non-inferiority of 0.001. In a sensitivity analysis excluding periprocedural myocardial infarction (POCE without PPMI), as used in the NOBLE trial, the POCE event rate was 9.7% in the SYNERGY group and 9.2% in the Supraflex Cruz group; the risk difference was not statistically significant. (Figure C) In a predefined subgroup analysis assessing POCE in the three strata of the anatomical (SYNTAX Score (SS≤22, 23-32, ≥33), the event rate in the highest strata of the Supraflex Cruz was numerically lower than in the SYNERGY arm. (14.6% in Supraflex Cruz and 22.8% in SYNERGY arm, p = 0.167)(Figure D) Conclusions In 3VD patients treated with the best PCI practice, the Supraflex Cruz stent is non-inferior to the SYNERGY stent in terms of POCE at one year. The potential superiority of the Supraflex Cruz in the most complex patients (SS ≥33) must be further investigated.For image description, please refer to the figure legend and surrounding text.