Hazırlayan: Dr. Özkan Karaca

Study Title:
The TARGET-IV Trial: International Multicenter Randomized Assessment of the Firehawk® Rapamycin Eluting Coronary Stent System

Conference: TCT 2024

Link: https://www.tctmd.com/slide/target-iv-trial-international-multicenter-randomized-assessment-firehawkr-rapamycin-eluting

Introduction
Drug-eluting stents (DES) reduce the risk of restenosis through controlled antiproliferative drug release; however, permanent polymers can delay the healing process and inhibit re-endothelialization. The Firehawk biodegradable polymer sirolimus-eluting stent (BP-SES) features a fully biodegradable sirolimus coating placed in deep abluminal grooves on the stent surface, delivering approximately one-third of the drug dose compared to other DES.

Objective
This study aims to present the primary findings of the TARGET-IV NA (Firehawk Rapamycin Target Eluting Coronary Stent North American Trial), a randomized controlled trial evaluating the clinical outcomes of BP-SES compared to existing second-generation DES.

Methods
The TARGET-IV NA study was designed as a prospective, multicenter, single-blind, 1:1 randomized noninferiority trial comparing BP-SES with control stents in patients diagnosed with chronic or acute coronary syndromes undergoing percutaneous coronary intervention (PCI). The primary endpoint was target lesion failure (TLF) occurring at 12 months, which included cardiac death, myocardial infarction related to the target vessel, or ischemic target lesion revascularization. The primary analysis was conducted using a 3.85% absolute margin and a one-sided ? value of 0.025 to test the noninferiority of BP-SES compared to the control group. Secondary endpoints with noninferiority power were evaluated in an optical coherence tomography (OCT) substudy (average neointimal hyperplasia thickness) and an angiographic substudy (in-stent late lumen loss).

Results
A total of 1,720 patients (mean age 66 years; 74% male) with 2,159 lesions were randomly assigned to receive BP-SES (860 patients, 1,057 lesions) or control second-generation DES (860 patients, 1,084 lesions). Of the participants, 61% had stable coronary artery disease, 32% had unstable angina, and 7% had non-ST segment elevation myocardial infarction (NSTEMI) or had recently experienced ST-segment elevation. The 12-month TLF rate in the BP-SES group was found to be non-inferior compared to the control group (3.4% vs. 3.3%; absolute risk difference 0.13, upper limit 97.5% CI: 2.03, P-noninferiority < 0.0001). Rates of cardiac death, myocardial infarction, and stent thrombosis were similar between the two groups. Angiographic follow-up was available for 104 patients (97.2% of those participating in the angiographic substudy) and 128 lesions (94.1%). At 13 months, the reinforced secondary endpoint of average in-stent late lumen loss was found to be 0.149 ± 0.263 mm for BP-SES and 0.327 ± 0.463 mm for control (least squares mean difference: -0.178; 90% CI: -0.2943 to -0.0632; Pnoninferiority < 0.0001). The optical coherence tomography substudy included 37 patients (42 lesions), and no difference in average neointimal hyperplasia thickness was observed between groups at 13 months (P-noninferiority = 0.01).

Conclusions
The biodegradable polymer sirolimus-eluting stent was found to be non-inferior to existing second-generation DES in terms of target lesion failure at 1 year. Additionally, all clinical outcomes evaluated at 1 year, including stent thrombosis, were similar between both treatment groups.

Commentary
This study found that percutaneous coronary interventions performed with the biodegradable polymer sirolimus-eluting stent (BP-SES) demonstrated comparable rates of target lesion failure and clinical outcomes within one year when compared to second-generation DES. Longer-term follow-up (5 years) is needed to determine whether these findings will impact efficacy and safety outcomes.