Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial

JAMA Neurol. 2022 Feb 1;79(2):176-184. doi: 10.1001/jamaneurol.2021.4804.

Authors

Baixue Jia¹, Xuelei Zhang², Ning Ma¹, Dapeng Mo¹, Feng Gao¹, Xuan Sun¹, Ligang Song¹, Lian Liu¹, Yiming Deng¹, Xiaotong Xu¹, Yong Zhang³, Zengpin Liu⁴, Sheng Guan⁵, Fan Zhang⁶, Bing Li⁷, Hongbo Zheng⁸, Xinfeng Liu⁹, Yajie Liu¹⁰, Kangning Chen¹¹, Jie Shuai¹², Jieqing Wan¹³, Jun Wang¹⁴, Xiangqun Shi¹⁵, Tianxiao Li¹⁶, Binge Chang¹⁷, David S Liebeskind¹⁸, Wengui Yu¹⁹, Zhongrong Miao¹; NOVA Trial Investigators

Collaborators

NOVA Trial Investigators:
Xiaochuan Huo, Xiaoqing Li, Gang Luo, Bo Wang, Wentao Gong, Tonghui Liu, Guangwen Li, Xianhui Su, Tao Quan, Guodong Xu, Liang Ma, Hongliang Wu, Huilong Zhang, Fayun Hu, Rui Liu, Qiushi Lv, Kaifeng Li, Guangjian Li, Fei Wei, Shenghao Ding, Hui Su, Guozhen Zhang, Ziliang Wang

Affiliations

¹ Interventional Neuroradiology Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Stroke Center, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
³ Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
⁴ Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
⁵ Neurointerventional Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
⁶ Department of Cerebrovascular Disease, Hainan General Hospital, Haikou, Hainan, China.
⁷ Department of Neurology, Yantai Yuhuangding Hospital, Yantai, Shandong, China.
⁸ Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁹ Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
¹⁰ Department of Neurology, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China.
¹¹ Department of Neurology, The Southwest Hospital of Army Medical University, Chongqing, China.
¹² Department of Neurology, Xinqiao Hospital, Army Medical University, Chongqing, China.
¹³ Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
¹⁴ Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing, China.
¹⁵ Department of Neurology, General Hospital of Lanzhou Military Command, Lanzhou, China.
¹⁶ Neurointerventional Department, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan, China.
¹⁷ Department of Neurosurgery, Tianjin First Central Hospital, Tianjin, China.
¹⁸ Department of Neurology, UCLA (University of California, Los Angeles).
¹⁹ Department of Neurology, University of California, Irvine, Irvine.

Abstract

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear.

Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS.

Design, settings, and participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021.

Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio.

Main outcomes and measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure.

Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46).

Conclusions and relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted.

Trial registration: ClinicalTrials.gov Identifier: NCT02578069.

Publication types

Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Constriction, Pathologic
Double-Blind Method
Drug-Eluting Stents* / adverse effects
Female
Follow-Up Studies
Graft Occlusion, Vascular / prevention & control
Humans
Intracranial Arteriosclerosis / therapy*
Ischemic Attack, Transient / mortality
Ischemic Attack, Transient / prevention & control
Male
Metals
Middle Aged
Prospective Studies
Recurrence
Risk
Stents* / adverse effects
Stroke / mortality
Stroke / prevention & control
Treatment Outcome

Substances

Metals

Associated data

ClinicalTrials.gov/NCT02578069