Randomized Comparison of Novel Low-Dose Sirolimus-Eluting Biodegradable Polymer Stent vs Second-Generation DES: TARGET-IV NA Trial

Robert W Yeh; Olivier F Bertrand; Ehtisham Mahmud; Emanuele Barbato; Batla Falah; Melek Ozgu Issever; Björn Redfors; Alexandra Popma; Michael Curtis; Niels van Royen; Jean-Francois Tanguay; Luc Janssens; William N Newman; Koen Teeuwen; James W Choi; Maurits T Dirksen; Akiko Maehara; Martin B Leon

doi:10.1016/j.jacc.2024.10.074

Randomized Comparison of Novel Low-Dose Sirolimus-Eluting Biodegradable Polymer Stent vs Second-Generation DES: TARGET-IV NA Trial

J Am Coll Cardiol. 2024 Oct 24:S0735-1097(24)09966-2. doi: 10.1016/j.jacc.2024.10.074. Online ahead of print.

Authors

Robert W Yeh¹, Olivier F Bertrand², Ehtisham Mahmud³, Emanuele Barbato⁴, Batla Falah⁵, Melek Ozgu Issever⁵, Björn Redfors⁶, Alexandra Popma⁵, Michael Curtis⁷, Niels van Royen⁸, Jean-Francois Tanguay⁹, Luc Janssens¹⁰, William N Newman¹¹, Koen Teeuwen¹², James W Choi¹³, Maurits T Dirksen¹⁴, Akiko Maehara¹⁵, Martin B Leon¹⁵

Affiliations

¹ Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: ryeh@bidmc.harvard.edu.
² Quebec Heart and Lung Institute, Quebec City, Quebec, Canada.
³ Division of Cardiovascular Medicine, University of California San Diego, La Jolla, California, USA.
⁴ Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
⁵ Clinical Trial Center, Cardiovascular Research Foundation, New York, New York, USA.
⁶ Clinical Trial Center, Cardiovascular Research Foundation, New York, New York, USA; Department of Population Health Sciences, Weill Cornell Medicine, New York, New York, USA; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
⁷ University of Calgary, Calgary, Alberta, Canada.
⁸ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁹ Montreal Heart Institute and Universite de Montreal, Montreal, Quebec, Canada.
¹⁰ Department of Cardiology, Imelda Hospital, Bonheiden, Belgium.
¹¹ North Carolina Heart and Vascular Research, Raleigh, North Carolina, USA.
¹² Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands.
¹³ Baylor Research Institute, Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas, USA.
¹⁴ Department of Cardiology, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands.
¹⁵ Clinical Trial Center, Cardiovascular Research Foundation, New York, New York, USA; NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York, USA.

PMID: 39480379
DOI: 10.1016/j.jacc.2024.10.074

Abstract

Background: Drug-eluting stents (DESs) with controlled antiproliferative drug release reduce restenosis risk, but durable polymers can delay healing and inhibit reendothelialization. The Firehawk biodegradable polymer sirolimus-eluting stent (BP-SES) has a fully biodegradable sirolimus-containing polymer coating localized to recessed abluminal grooves on the stent surface and delivers roughly one-third the drug dose of other DESs.

Objectives: We report the primary results of the TARGET-IV NA (Firehawk Rapamycin Target Eluting Coronary Stent North American Trial) randomized controlled trial comparing clinical outcomes with BP-SES vs currently used second-generation DESs.

Methods: The TARGET-IV NA study was a prospective, multicenter, single-blind, 1:1 randomized noninferiority trial comparing the BP-SES with control in North America and Europe among patients undergoing percutaneous coronary intervention for chronic or acute coronary syndromes. The primary endpoint was target lesion failure (TLF) at 12 months (composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization). The primary analysis (intention-to-treat) tested noninferiority of BP-SES vs control using an absolute margin of 3.85% and 1-sided α of 0.025. Noninferiority-powered secondary endpoints were tested in an optical coherence tomography substudy (endpoint: mean neointimal hyperplasia thickness) and an angiography substudy (endpoint: in-stent late lumen loss).

Results: A total of 1,720 patients (mean age 66 years; 74% male) with 2,159 lesions were randomly allocated to receive either BP-SES (860 patients, 1,057 lesions) or control second-generation DES (860 patients, 1,084 lesions). A total of 61% of patients presented with stable coronary disease, 32% had unstable angina, and 7% had non-ST-segment elevation myocardial infarction (NSTEMI) or recent ST-segment elevation myocardial infarction. The rate of TLF with BP-SES was noninferior to control at 12 months (3.4% vs 3.3%, absolute risk difference 0.13%, upper bound 97.5% CI: 2.03, P_{noninferiority} < 0.0001). Cardiac death, myocardial infarction, and stent thrombosis rates were similar between groups. Angiographic follow-up was available in 104 patients (97.2% of those enrolled in the angiographic substudy) and 128 (94.1%) lesions. At 13 months, the powered secondary endpoint of mean in-stent late lumen loss was 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; P_{noninferiority} < 0.0001). The optical coherence tomography substudy included 37 patients (42 lesions) with no difference in mean neointimal hyperplasia thickness between groups at 13 months (P_{noninferiority} = 0.01).

Conclusions: The biodegradable polymer sirolimus-eluting stent was noninferior to currently used second-generation DES with regard to TLF at 1 year. (Firehawk® Rapamycin Target Eluting Coronary Stent North American Trial; NCT04562532).

Keywords: Firehawk; TARGET-IV NA; drug-eluting stent; randomized clinical trial; target lesion failure.

Associated data

ClinicalTrials.gov/NCT04562532