Abstract: Background Coronary heart disease (CHD) is a major public health issue in China, and antiplatelet therapy forms the cornerstone of secondary prevention. Under the context of routine national centralized procurement of medicines, there remains a significant difference in the annual treatment costs between clopidogrel and aspirin. However, there is currently a lack of studies based on real-world healthcare costs in China that systematically evaluate the economic effectiveness of these two drugs for secondary prevention of CHD following centralized procurement. Objective To evaluate the cost-effectiveness of clopidogrel monotherapy versus aspirin for the long-term secondary prevention of CHD from the perspective of the Chinese healthcare system. Methods Based on the individual patient data meta-analysis published by Valgimigli et al. in The Lancet, a Markov model was constructed to simulate the 20-year disease progression of patients. The model included the following health states: event-free, post-myocardial infarction (acute/chronic), post-stroke (acute/chronic), post-bleeding, cardiovascular death, and non-cardiovascular death. The simulated cohort had a mean starting age of 65 years, with 78.6% male. Cost parameters were derived from the Tianjin Urban Employee Medical Insurance database (2019-2021, covering approximately 5.2 million enrollees), and published studies. Health utility values were obtained from EQ-5D studies in the Chinese population. Quality-adjusted life years (QALY) were used as the outcome measure, with half-cycle correction applied, and both costs and health outcomes were discounted at an annual rate of 5%. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess parameter uncertainty. Results The base-case analysis showed that over a 20-year simulation horizon, compared to the aspirin group, the clopidogrel group gained an additional 0.09 quality-adjusted life years (QALY) per patient while increasing medical costs by ¥9 373.74, resulting in an ICER of ¥98 729.16 per QALY gained. Using China's 2025 per capita GDP (¥99 665) as the willingness-to-pay (WTP) threshold, clopidogrel demonstrated a certain cost-effectiveness advantage under current parameters. Sensitivity analyses indicated that the ICER was sensitive to parameters such as the annual incidence of cardiovascular death and stroke. When the willingnesstopay threshold was raised to the level of one times the per capita gross domestic product (¥99 665/QALY), clopidogrel had a probability of being costeffective of approximately 53.2%; when the threshold was increased to approximately three times the per capita GDP (¥298 995/QALY), that probability increased to approximately 71.0%. Conclusion Under current volume-based procurement prices, clopidogrel monotherapy for routine secondary prevention of CHD lies in a marginal cost-effectiveness range compared with aspirin (base-case ICER ¥98 729 per QALY, slightly below the WTP threshold of ¥99 665, i.e., one times the per capita GDP). Probabilistic sensitivity analysis showed that at a WTP of ¥99 665, the probability of clopidogrel being cost-effective was approximately 53.2%. Given a manageable impact on the healthcare budget and combined with risk stratification using CYP2C19 genotyping, clopidogrel could be considered as one option for routine secondary prevention, but indiscriminate substitution for aspirin in all patients is not recommended.

Key words: Clopidogrel, Aspirin, Secondary prevention of coronary heart disease, Pharmacoeconomic evaluation, Markov model, Cost-effectiveness analysis

摘要： 背景 冠心病是我国重大公共卫生问题，抗血小板治疗是二级预防的基石。国家药品集中带量采购常态化背景下，氯吡格雷与阿司匹林年治疗费用仍存在显著差异。目前尚缺乏基于中国真实世界医疗成本、系统评估集采后两者用于冠心病二级预防经济性的研究。目的 从中国医疗卫生体系角度，评价氯吡格雷对比阿司匹林用于冠心病患者长期二级预防的经济性。方法 基于Valgimigli等发表于The Lancet的个体患者数据Meta分析，构建马尔可夫（Markov）模型模拟患者20年疾病进程。模型预设的健康状态包括：无事件、心肌梗死后（急性期/稳定期）、脑卒中后（急性期/稳定期）、出血后、心血管死亡及非心血管死亡。研究队列初始年龄设定为65岁，男性占比78.6%。成本参数来源于天津城镇职工医保数据库（2019—2021年，约520万参保人群）及已发表研究。健康效用值基于中国人群EQ-5D量表研究获取。以质量调整生命年（QALY）为效果指标，采用半循环校正，成本和健康产出均以5%年贴现率贴现。采用单因素敏感性分析和概率敏感性分析评估参数不确定性。结果 基础分析显示，在20年模拟期内，与阿司匹林组相比，氯吡格雷组每人多获得0.09个QALY，同时增加医疗成本9 373.74元，增量成本-效果比（ICER）为98 729.16元/QALY。以2025年中国人均国内生产总值（99 665元）作为支付意愿（WTP）阈值，氯吡格雷在当前参数下表现出一定的成本-效果优势。敏感性分析显示，ICER对心血管死亡发生率、脑卒中发生率等参数较为敏感；当WTP阈值提升至1倍人均GDP（99 665元/QALY）时，氯吡格雷具有成本-效果的概率约为53.2%；当WTP阈值提高至约3倍人均GDP（298 995元/QALY）时，该概率升至约71.0%。结论 当前集采价格下，氯吡格雷单药相对于阿司匹林用于常规冠心病二级预防处于边际成本-效果区间（基础分析ICER 98 729元/QALY，略低于1倍人均GDP的WTP阈值99 665元）。概率敏感性分析显示，在WTP为99 665元时氯吡格雷具有成本-效果的概率约为53.2%。在医保预算影响可控且结合CYP2C19基因检测进行风险分层的前提下，氯吡格雷可作为常规二级预防的选择之一，但不推荐不加选择地全面替代阿司匹林。

关键词: 氯吡格雷, 阿司匹林, 冠心病二级预防, 药物经济学评价, Markov 模型, 成本 - 效果分析