Case Report: Shifting the paradigm in refractory in-stent restenosis: systemic immunomodulation with hydroxychloroquine and sirolimus
- 1Department of Integrative Medicine Cardiology, China-Japan Friendship Hospital
- 2Graduate School, Beijing University of Chinese Medicine
Abstract
Background: Recurrent in-stent restenosis (ISR) refractory to repeated percutaneous interventions remains a formidable clinical challenge. Despite the established efficacy of drug-coated balloons (DCBs) and drug-eluting stents, a subset of patients experience relentless restenosis, highlighting the need for novel systemic strategies targeting underlying pathophysiological drivers.
Objectives: To describe a case of extreme, refractory recurrent ISR that failed multiple DCB interventions but was associated with a marked response to systemic therapy with Hydroxychloroquine (HCQ) and Sirolimus, and to discuss the mechanistic rationale and potential clinical implications.
Methods: A 56-year-old female presented with rapidly recurring ISR in both the left anterior descending (LAD) and right coronary arteries (RCA). Over a 6-year period, she underwent 11 interventional procedures at our center and at outside institutions. Sequential trials of oral anti-inflammatory agents failed to halt the restenosis cycle. In May 2023, HCQ was initiated, and Sirolimus was added in October 2023. Serial angiographic and intravascular ultrasound (IVUS) follow-up were performed.
Results: Prior to systemic therapy, restenosis occurred every 6 months in both vessels. After initiating HCQ and Sirolimus, the RCA remained free of restenosis for over one year. The LAD, while requiring additional focal DCB treatments, showed a marked reduction in restenosis burden, with disease becoming highly localized. IVUS revealed neointimal hyperplasia with superimposed lipid-rich and fibrous plaques, without evidence of stent fracture or malapposition.
Conclusions: In a patient with recurrent ISR, targeted systemic immunomodulation with HCQ and Sirolimus was associated with sustained vessel patency and reduced restenosis burden. This case provides a hypothesis-generating observation that addressing systemic inflammatory and proliferative drivers may repersent a potential salvage strategy for refractory recurrent ISR, warranting further prospective investigation.
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BibTeX
@article{liao2026case,
title = {{Case Report: Shifting the paradigm in refractory in-stent restenosis: systemic immunomodulation with hydroxychloroquine and sirolimus}},
author = {Jiangquan Liao and Yan Wang and Jie Zhang and Tianshu Xie and Peng Yang and Lin Zhao and Tong Gao and Qian Wang and Jiejia Liang and Qian Li and Weidong Hong and Ke Dong and Changhong Zhao and Di Wang and Xianlun Li and Mingjing Shao},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1886312},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1886312/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: Shifting the paradigm in refractory in-stent restenosis: systemic immunomodulation with hydroxychloroquine and sirolimus
AU - Jiangquan Liao
AU - Yan Wang
AU - Jie Zhang
AU - Tianshu Xie
AU - Peng Yang
AU - Lin Zhao
AU - Tong Gao
AU - Qian Wang
AU - Jiejia Liang
AU - Qian Li
AU - Weidong Hong
AU - Ke Dong
AU - Changhong Zhao
AU - Di Wang
AU - Xianlun Li
AU - Mingjing Shao
PY - 2026
DA - 2026/10/28
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1886312
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1886312/full
AB - Background: Recurrent in-stent restenosis (ISR) refractory to repeated percutaneous interventions remains a formidable clinical challenge. Despite the established efficacy of drug-coated balloons (DCBs) and drug-eluting stents, a subset of patients experience relentless restenosis, highlighting the need for novel systemic strategies targeting underlying pathophysiological drivers. Objectives: To describe a case of extreme, refractory recurrent ISR that failed multiple DCB interventions but was associated with a marked response to systemic therapy with Hydroxychloroquine (HCQ) and Sirolimus, and to discuss the mechanistic rationale and potential clinical implications. Methods: A 56-year-old female presented with rapidly recurring ISR in both the left anterior descending (LAD) and right coronary arteries (RCA). Over a 6-year period, she underwent 11 interventional procedures at our center and at outside institutions. Sequential trials of oral anti-inflammatory agents failed to halt the restenosis cycle. In May 2023, HCQ was initiated, and Sirolimus was added in October 2023. Serial angiographic and intravascular ultrasound (IVUS) follow-up were performed. Results: Prior to systemic therapy, restenosis occurred every 6 months in both vessels. After initiating HCQ and Sirolimus, the RCA remained free of restenosis for over one year. The LAD, while requiring additional focal DCB treatments, showed a marked reduction in restenosis burden, with disease becoming highly localized. IVUS revealed neointimal hyperplasia with superimposed lipid-rich and fibrous plaques, without evidence of stent fracture or malapposition. Conclusions: In a patient with recurrent ISR, targeted systemic immunomodulation with HCQ and Sirolimus was associated with sustained vessel patency and reduced restenosis burden. This case provides a hypothesis-generating observation that addressing systemic inflammatory and proliferative drivers may repersent a potential salvage strategy for refractory recurrent ISR, warranting further prospective investigation.
SN - 2297-055X
ER -