Cost-Effectiveness of Low-Dose Compared to Standard-Dose Alteplase for Acute Ischemic Stroke in China: A Within-Trial Economic Evaluation of the ENCHANTED Study

Lei Si; Xiaoying Chen; Menglu Ouyang; Xia Wang; Guofang Chen; Yong-Jun Cao; Guojun Wu; Jinli Zhang; Jingfen Zhang; YuKai Liu; Shihong Zhang; Lili Song; Candice Delcourt; Hisatomi Arima; Lidan Wang; Thomas Lung; Mingsheng Chen; Craig S Anderson; Stephen Jan; ENCHANTED Investigators

doi:10.1159/000525869

Cost-Effectiveness of Low-Dose Compared to Standard-Dose Alteplase for Acute Ischemic Stroke in China: A Within-Trial Economic Evaluation of the ENCHANTED Study

Cerebrovasc Dis. 2023;52(2):145-152. doi: 10.1159/000525869. Epub 2022 Aug 31.

Authors

Lei Si^{1

2}, Xiaoying Chen^{3

4

5}, Menglu Ouyang¹, Xia Wang¹, Guofang Chen⁶, Yong-Jun Cao⁷, Guojun Wu⁸, Jinli Zhang⁹, Jingfen Zhang¹⁰, YuKai Liu¹¹, Shihong Zhang¹², Lili Song^{1

13

14}, Candice Delcourt^{1

15}, Hisatomi Arima^{1

16}, Lidan Wang¹⁷, Thomas Lung^{1

18}, Mingsheng Chen², Craig S Anderson^{1

18

13

19

20}, Stephen Jan¹; ENCHANTED Investigators

Affiliations

¹ The George Institute for Global Health, University of New South Wales, Kensington, New South Wales, Australia.
² School of Health Policy & Management, Nanjing Medical University, Nanjing, China.
³ The George Institute for Global Health, University of New South Wales, Kensington, New South Wales, Australia, xchen@georgeinstitute.org.au.
⁴ Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia, xchen@georgeinstitute.org.au.
⁵ The George Institute China at Peking University Health Science Centre, Beijing, China, xchen@georgeinstitute.org.au.
⁶ Xuzhou Central Hospital, Xuzhou, China.
⁷ The Second Affiliated Hospital of Soochow University, Soochow, China.
⁸ Hebei Yutian County Hospital, Tangshan, China.
⁹ The People's Liberation Army No. 263 Hospital, Beijing, China.
¹⁰ Inner Mongolia Baotou City Central Hospital, Baotou, China.
¹¹ The First Hospital of Nanjing, Nanjing, China.
¹² West China Hospital Sichuan University, Chengdu, China.
¹³ The George Institute China at Peking University Health Science Centre, Beijing, China.
¹⁴ The People's Liberation Army No. 85 Hospital, Shanghai, China.
¹⁵ Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
¹⁶ Department of Preventive Medicine and Public Health, Fukuoka University, Fukuoka, Japan.
¹⁷ School of Health Management, Anhui Medical University, Hefei, China.
¹⁸ Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
¹⁹ Neurology Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
²⁰ Heart Health Research Center, Beijing, China.

PMID: 36044836
DOI: 10.1159/000525869

Abstract

Introduction: The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) showed that a low-dose alteplase was safe but not clearly non-inferior to standard-dose alteplase in acute ischemic stroke (AIS). Given the significant cost of this medicine, we undertook a cost-effectiveness analysis to determine the probability that low-dose is cost-effective relative to standard-dose alteplase in China.

Methods: For ENCHANTED participants in China with available health cost data, cost-effectiveness and cost-utility analyses were undertaken in which death or disability (modified Rankin scale scores 2-6) at 90 days and quality-adjusted life-years (QALYs) were used as outcome measures, respectively. There was adherence to standard guidelines for health economic evaluations alongside non-inferiority trials and according to a health-care payer's perspective. The equivalence margin for cost and effectiveness was set at USD 691 and -0.025 QALYs, respectively, for the base-case analysis. Probabilistic sensitivity analyses were used to evaluate the probability of low-dose alteplase being non-inferior.

Results: While the mean cost of alteplase was lower in the low-dose group (USD 1,569 vs. USD 2,154 in the standard-dose group), the total cost was USD 56 (95% confidence interval [CI]: -1,000-1,113) higher compared to the standard-dose group due to higher hospitalization costs in the low-dose group. There were 462 (95% CI: 415-509) and 410 (95% CI: 363-457) patients with death or disability per 1,000 patients in the low-dose and standard-dose groups, respectively. The low-dose group had marginally lower (0.008, 95% CI: -0.016-0.001) QALYs compared to their standard-dose counterparts. The low-dose group was found to have an 88% probability of being non-inferior based on cost-effectiveness versus the standard-dose group.

Conclusions: This health economic evaluation alongside the ENCHANTED indicates that the use of low-dose alteplase does not save overall healthcare costs nor lead to a gain in QALYs in the management of Chinese patients with AIS compared to the use of standard dose. There is little justification on economic grounds to shift from standard-of-care thrombolysis in AIS.

Keywords: Acute ischemic stroke; Alteplase; Clinical trial; Cost-effectiveness; Health economics.

MeSH terms

Brain Ischemia*
China
Cost-Benefit Analysis
Fibrinolytic Agents / adverse effects
Humans
Ischemic Stroke* / drug therapy
Stroke*
Tissue Plasminogen Activator / adverse effects
Treatment Outcome

Substances

Tissue Plasminogen Activator
Fibrinolytic Agents