Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial

the REC-CAGEFREE I Investigators; Ling Tao; Xingqiang He; Guidong Shen; Mingxing Wu; Yuquan He; Likun Ma; Feng Yang; Zheng Ji; Hua Wang; Yanqing Wu; Zhenfei Fang; Hong Jiang; Shangyu Wen; Yuanzhe Jin; Hui Chen; Lin Zhong; Sigan Hu; Yi Liu; Fei Li; Jingyu Zhou; Fan Ouyang; Zhihui Zhang; Bin Zhu; Ruining Zhang; Guotao Fu; Jianzheng Liu; Zhiwei Jiang; Duolao Wang; Davide Capodanno; Scot Garg; Yoshinobu Onuma; Patrick W. Serruys; Chao Gao

doi:10.1016/j.jacc.2025.10.027

Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial

the REC-CAGEFREE I Investigators
, Ling Tao
, Xingqiang He
, Guidong Shen
, Mingxing Wu
, Yuquan He
, Likun Ma
, Feng Yang
, Zheng Ji
, Hua Wang
, Yanqing Wu
, Zhenfei Fang
, Hong Jiang
, Shangyu Wen
, Yuanzhe Jin
, Hui Chen
, Lin Zhong
, Sigan Hu
, Yi Liu
, Fei Li

Jingyu Zhou, Fan Ouyang, Zhihui Zhang, Bin Zhu, Ruining Zhang, Guotao Fu, Jianzheng Liu, Zhiwei Jiang, Duolao Wang, Davide Capodanno, Scot Garg, Yoshinobu Onuma, Patrick W. Serruys, Chao Gao

Clinical Sciences

Xijing Hospital
University of Galway
Ankang Hospital of Traditional Chinese Medicine
Xiangtan Central Hospital
Jilin University
University of Science and Technology of China
First Hospital of Kunming
Tangshan Workers Hospital
Sichuan University
Nanchang University
Central South University
Renmin Hospital of Wuhan University
Tianjin Fourth Central Hospital
China Medical University
Capital Medical University
Yantai Yuhuangding Hospital
Bengbu Medical College
Southwest Hospital of AMU
Beijing KeyTech Statistical Consulting
University of Catania
East Lancashire Hospitals NHS Trust
University of Central Lancashire

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Background: Owing to the absence of a metallic scaffold, percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) may cause less chronic inflammation and potentially reduce late complications compared with drug-eluting stents (DES). However, in the REC-CAGEFREE I study, the strategy of DCB angioplasty with rescue stenting failed to achieve noninferiority to intended DES implantation for treating de novo lesions at 2 years. Objective: This study sought to investigate the 3-year outcomes of the REC-CAGEFREE I trial and assess the mid-term effects of DCBs compared with DES.

Methods: REC-CAGEFREE I was an open-label, randomized, noninferiority trial conducted across 43 sites in China. After successful lesion predilation, 2,272 patients with de novo coronary artery disease (regardless of target vessel diameter) were randomly assigned (1:1) to paclitaxel-coated balloon angioplasty with the option of rescue stenting (DCB arm) vs up-front deployment of second-generation thin-strut sirolimus-eluting stents (DES arm). The primary outcome was the device-oriented composite endpoint (DOCE; including cardiovascular death, target vessel myocardial infarction [TV-MI], and clinically and physiologically indicated target lesion revascularization [CPI-TLR]) assessed in the intention-to-treat population. The extended follow-up is ongoing and will continue for up to 10 years.

Results: From February 5, 2021, to May 1, 2022, 1,133 patients were randomly assigned to the DCB arm and 1,139 to the DES arm. The median diameter of devices was at 3.00 ± 0.46 mm. Rescue DES implantation after unsatisfactory DCB angioplasty was performed in 106 patients (9.4%). At 3 years, the DOCE occurred in 92 patients (8.2%) in the DCB arm and 56 (5.0%) in the DES arm (difference: 3.21%; 95% CI: 1.17%-5.26%; P = 0.002). Landmark analyses showed that the rates of difference in the DOCE at 0 to 1, 1 to 2, and 2 to 3 years were 1.69% (95% CI: 0.32%-3.06%), 1.10% (95% CI: −0.13% to 2.32%), and 0.58% (95% CI: −0.51% to 1.66%), respectively (P_trend = 0.023).

Conclusions: In patients with de novo coronary artery disease, DCB angioplasty with rescue stenting was associated with a higher rate of the DOCE compared with up-front DES implantation regarding the DOCE at 3 years.

Original language	English
Pages (from-to)	312-329
Number of pages	18
Journal	Journal of the American College of Cardiology
Volume	87
Issue number	3
Early online date	27 Oct 2025
DOIs	https://doi.org/10.1016/j.jacc.2025.10.027
Publication status	Published - 27 Jan 2026

Keywords

de novo coronary artery disease
drug-coated balloon
drug-eluting stents

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Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD 3 Year Follow-Up of REC-CAGEFREE I TrialAccepted author manuscript, 1.24 MBLicence: CC BY

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the REC-CAGEFREE I Investigators, Tao, L., He, X., Shen, G., Wu, M., He, Y., Ma, L., Yang, F., Ji, Z., Wang, H., Wu, Y., Fang, Z., Jiang, H., Wen, S., Jin, Y., Chen, H., Zhong, L., Hu, S., Liu, Y., ... Gao, C. (2026). Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial. Journal of the American College of Cardiology, 87(3), 312-329. https://doi.org/10.1016/j.jacc.2025.10.027

@article{6689b8bb58f94870922477270ba128fc,

title = "Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial",

abstract = "Background: Owing to the absence of a metallic scaffold, percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) may cause less chronic inflammation and potentially reduce late complications compared with drug-eluting stents (DES). However, in the REC-CAGEFREE I study, the strategy of DCB angioplasty with rescue stenting failed to achieve noninferiority to intended DES implantation for treating de novo lesions at 2 years. Objective: This study sought to investigate the 3-year outcomes of the REC-CAGEFREE I trial and assess the mid-term effects of DCBs compared with DES. Methods: REC-CAGEFREE I was an open-label, randomized, noninferiority trial conducted across 43 sites in China. After successful lesion predilation, 2,272 patients with de novo coronary artery disease (regardless of target vessel diameter) were randomly assigned (1:1) to paclitaxel-coated balloon angioplasty with the option of rescue stenting (DCB arm) vs up-front deployment of second-generation thin-strut sirolimus-eluting stents (DES arm). The primary outcome was the device-oriented composite endpoint (DOCE; including cardiovascular death, target vessel myocardial infarction [TV-MI], and clinically and physiologically indicated target lesion revascularization [CPI-TLR]) assessed in the intention-to-treat population. The extended follow-up is ongoing and will continue for up to 10 years. Results: From February 5, 2021, to May 1, 2022, 1,133 patients were randomly assigned to the DCB arm and 1,139 to the DES arm. The median diameter of devices was at 3.00 ± 0.46 mm. Rescue DES implantation after unsatisfactory DCB angioplasty was performed in 106 patients (9.4\%). At 3 years, the DOCE occurred in 92 patients (8.2\%) in the DCB arm and 56 (5.0\%) in the DES arm (difference: 3.21\%; 95\% CI: 1.17\%-5.26\%; P = 0.002). Landmark analyses showed that the rates of difference in the DOCE at 0 to 1, 1 to 2, and 2 to 3 years were 1.69\% (95\% CI: 0.32\%-3.06\%), 1.10\% (95\% CI: −0.13\% to 2.32\%), and 0.58\% (95\% CI: −0.51\% to 1.66\%), respectively (Ptrend = 0.023). Conclusions: In patients with de novo coronary artery disease, DCB angioplasty with rescue stenting was associated with a higher rate of the DOCE compared with up-front DES implantation regarding the DOCE at 3 years.",

keywords = "de novo coronary artery disease, drug-coated balloon, drug-eluting stents",

author = "\{the REC-CAGEFREE I Investigators\} and Ling Tao and Xingqiang He and Guidong Shen and Mingxing Wu and Yuquan He and Likun Ma and Feng Yang and Zheng Ji and Hua Wang and Yanqing Wu and Zhenfei Fang and Hong Jiang and Shangyu Wen and Yuanzhe Jin and Hui Chen and Lin Zhong and Sigan Hu and Yi Liu and Fei Li and Jingyu Zhou and Fan Ouyang and Zhihui Zhang and Bin Zhu and Ruining Zhang and Guotao Fu and Jianzheng Liu and Zhiwei Jiang and Duolao Wang and Davide Capodanno and Scot Garg and Yoshinobu Onuma and Serruys, \{Patrick W.\} and Chao Gao",

year = "2026",

month = jan,

day = "27",

doi = "10.1016/j.jacc.2025.10.027",

language = "English",

volume = "87",

pages = "312--329",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "3",

}

the REC-CAGEFREE I Investigators, Tao, L, He, X, Shen, G, Wu, M, He, Y, Ma, L, Yang, F, Ji, Z, Wang, H, Wu, Y, Fang, Z, Jiang, H, Wen, S, Jin, Y, Chen, H, Zhong, L, Hu, S, Liu, Y, Li, F, Zhou, J, Ouyang, F, Zhang, Z, Zhu, B, Zhang, R, Fu, G, Liu, J, Jiang, Z, Wang, D, Capodanno, D, Garg, S, Onuma, Y, Serruys, PW & Gao, C 2026, 'Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial', Journal of the American College of Cardiology, vol. 87, no. 3, pp. 312-329. https://doi.org/10.1016/j.jacc.2025.10.027

TY - JOUR

T1 - Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial

AU - the REC-CAGEFREE I Investigators

AU - Tao, Ling

AU - He, Xingqiang

AU - Shen, Guidong

AU - Wu, Mingxing

AU - He, Yuquan

AU - Ma, Likun

AU - Yang, Feng

AU - Ji, Zheng

AU - Wang, Hua

AU - Wu, Yanqing

AU - Fang, Zhenfei

AU - Jiang, Hong

AU - Wen, Shangyu

AU - Jin, Yuanzhe

AU - Chen, Hui

AU - Zhong, Lin

AU - Hu, Sigan

AU - Liu, Yi

AU - Li, Fei

AU - Zhou, Jingyu

AU - Ouyang, Fan

AU - Zhang, Zhihui

AU - Zhu, Bin

AU - Zhang, Ruining

AU - Fu, Guotao

AU - Liu, Jianzheng

AU - Jiang, Zhiwei

AU - Wang, Duolao

AU - Capodanno, Davide

AU - Garg, Scot

AU - Onuma, Yoshinobu

AU - Serruys, Patrick W.

AU - Gao, Chao

PY - 2026/1/27

Y1 - 2026/1/27

N2 - Background: Owing to the absence of a metallic scaffold, percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) may cause less chronic inflammation and potentially reduce late complications compared with drug-eluting stents (DES). However, in the REC-CAGEFREE I study, the strategy of DCB angioplasty with rescue stenting failed to achieve noninferiority to intended DES implantation for treating de novo lesions at 2 years. Objective: This study sought to investigate the 3-year outcomes of the REC-CAGEFREE I trial and assess the mid-term effects of DCBs compared with DES. Methods: REC-CAGEFREE I was an open-label, randomized, noninferiority trial conducted across 43 sites in China. After successful lesion predilation, 2,272 patients with de novo coronary artery disease (regardless of target vessel diameter) were randomly assigned (1:1) to paclitaxel-coated balloon angioplasty with the option of rescue stenting (DCB arm) vs up-front deployment of second-generation thin-strut sirolimus-eluting stents (DES arm). The primary outcome was the device-oriented composite endpoint (DOCE; including cardiovascular death, target vessel myocardial infarction [TV-MI], and clinically and physiologically indicated target lesion revascularization [CPI-TLR]) assessed in the intention-to-treat population. The extended follow-up is ongoing and will continue for up to 10 years. Results: From February 5, 2021, to May 1, 2022, 1,133 patients were randomly assigned to the DCB arm and 1,139 to the DES arm. The median diameter of devices was at 3.00 ± 0.46 mm. Rescue DES implantation after unsatisfactory DCB angioplasty was performed in 106 patients (9.4%). At 3 years, the DOCE occurred in 92 patients (8.2%) in the DCB arm and 56 (5.0%) in the DES arm (difference: 3.21%; 95% CI: 1.17%-5.26%; P = 0.002). Landmark analyses showed that the rates of difference in the DOCE at 0 to 1, 1 to 2, and 2 to 3 years were 1.69% (95% CI: 0.32%-3.06%), 1.10% (95% CI: −0.13% to 2.32%), and 0.58% (95% CI: −0.51% to 1.66%), respectively (Ptrend = 0.023). Conclusions: In patients with de novo coronary artery disease, DCB angioplasty with rescue stenting was associated with a higher rate of the DOCE compared with up-front DES implantation regarding the DOCE at 3 years.

AB - Background: Owing to the absence of a metallic scaffold, percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) may cause less chronic inflammation and potentially reduce late complications compared with drug-eluting stents (DES). However, in the REC-CAGEFREE I study, the strategy of DCB angioplasty with rescue stenting failed to achieve noninferiority to intended DES implantation for treating de novo lesions at 2 years. Objective: This study sought to investigate the 3-year outcomes of the REC-CAGEFREE I trial and assess the mid-term effects of DCBs compared with DES. Methods: REC-CAGEFREE I was an open-label, randomized, noninferiority trial conducted across 43 sites in China. After successful lesion predilation, 2,272 patients with de novo coronary artery disease (regardless of target vessel diameter) were randomly assigned (1:1) to paclitaxel-coated balloon angioplasty with the option of rescue stenting (DCB arm) vs up-front deployment of second-generation thin-strut sirolimus-eluting stents (DES arm). The primary outcome was the device-oriented composite endpoint (DOCE; including cardiovascular death, target vessel myocardial infarction [TV-MI], and clinically and physiologically indicated target lesion revascularization [CPI-TLR]) assessed in the intention-to-treat population. The extended follow-up is ongoing and will continue for up to 10 years. Results: From February 5, 2021, to May 1, 2022, 1,133 patients were randomly assigned to the DCB arm and 1,139 to the DES arm. The median diameter of devices was at 3.00 ± 0.46 mm. Rescue DES implantation after unsatisfactory DCB angioplasty was performed in 106 patients (9.4%). At 3 years, the DOCE occurred in 92 patients (8.2%) in the DCB arm and 56 (5.0%) in the DES arm (difference: 3.21%; 95% CI: 1.17%-5.26%; P = 0.002). Landmark analyses showed that the rates of difference in the DOCE at 0 to 1, 1 to 2, and 2 to 3 years were 1.69% (95% CI: 0.32%-3.06%), 1.10% (95% CI: −0.13% to 2.32%), and 0.58% (95% CI: −0.51% to 1.66%), respectively (Ptrend = 0.023). Conclusions: In patients with de novo coronary artery disease, DCB angioplasty with rescue stenting was associated with a higher rate of the DOCE compared with up-front DES implantation regarding the DOCE at 3 years.

KW - de novo coronary artery disease

KW - drug-coated balloon

KW - drug-eluting stents

U2 - 10.1016/j.jacc.2025.10.027

DO - 10.1016/j.jacc.2025.10.027

M3 - Article

C2 - 41194754

AN - SCOPUS:105022875961

SN - 0735-1097

VL - 87

SP - 312

EP - 329

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 3

ER -

Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial

Abstract

Keywords

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