Greenhalgh Janette, Bagust Adrian, Boland Angela, Dwan Kerry, Beale Sophie, Fleeman Nigel, McEntee Joanne, Dundar Yenal, Richardson Marty, Fisher Michael
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
North West Medicines Information Centre, Pharmacy Practice Unit, Liverpool, UK.
Health Technol Assess. 2015 Apr;19(29):1-130. doi: 10.3310/hta19290.
Acute coronary syndromes (ACSs) are life-threatening conditions associated with acute myocardial ischaemia. There are three main types of ACS: ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). One treatment for ACS is percutaneous coronary intervention (PCI) plus adjunctive treatment with antiplatelet drugs. Dual therapy antiplatelet treatment [aspirin plus either prasugrel (Efient(®), Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd), clopidogrel or ticagrelor (Brilique(®), AstraZeneca)] is standard in UK clinical practice. Prasugrel is the focus of this review.
The remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182.
Four electronic databases (MEDLINE, EMBASE, The Cochrane Library, PubMed) were searched from database inception to June 2013 for randomised controlled trials (RCTs) and to August 2013 for economic evaluations comparing prasugrel with clopidogrel or ticagrelor in ACS patients undergoing PCI.
Clinical outcomes included non-fatal and fatal cardiovascular (CV) events, adverse effects of treatment and health-related quality of life (HRQoL). Cost-effectiveness outcomes included incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. An independent economic model assessed four mutually exclusive subgroups: ACS patients treated with PCI for STEMI and with and without diabetes mellitus and ACS patients treated with PCI for UA or NSTEMI and with and without diabetes mellitus.
No new RCTs were identified beyond that reported in TA182. TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38) compared prasugrel with clopidogrel in ACS patients scheduled for PCI. No relevant economic evaluations were identified. Our analyses focused on a key subgroup of patients: those aged < 75 years who weighed > 60 kg (no previous stroke or transient ischaemic attack). For the primary composite end point (death from CV causes, non-fatal myocardial infarction or non-fatal stroke) statistically significantly fewer events occurred in the prasugrel arm (8.3%) than in the clopidogrel arm (11%). No statistically significant difference in major bleeding events was noted. However, there was a significant difference in favour of clopidogrel when major and minor bleeding events were combined (3.0 vs. 3.9%). No conclusions could be drawn regarding HRQoL. The results of sensitivity analyses confirmed that it is likely that, for all four ACS subgroups, within 5-10 years prasugrel is a cost-effective treatment option compared with clopidogrel at a willingness-to-pay threshold of £20,000 to £30,000 per QALY gained. At the full 40-year time horizon, all estimates are < £10,000 per QALY gained.
Lack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. The long-term modelling exercise is vulnerable to major assumptions about the continuation of early health outcome gains.
A key strength of the review is that it demonstrates the cost-effectiveness of prasugrel compared with clopidogrel using the generic price of clopidogrel. Although the report demonstrates the cost-effectiveness of prasugrel compared with clopidogrel at a threshold of £20,000 to £30,000 per QALY gained, the long-term modelling is vulnerable to major assumptions regarding long-term gains. Lack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. Well-audited data are needed from a long-term UK clinical registry on defined ACS patient groups treated with PCI who receive prasugrel, ticagrelor and clopidogrel.
This study is registered as PROSPERO CRD42013005047.
The National Institute for Health Research Health Technology Assessment programme.
急性冠状动脉综合征（ACS）是与急性心肌缺血相关的危及生命的疾病。ACS主要有三种类型：ST段抬高型心肌梗死（STEMI）、非ST段抬高型心肌梗死（NSTEMI）和不稳定型心绞痛（UA）。ACS的一种治疗方法是经皮冠状动脉介入治疗（PCI）加用抗血小板药物辅助治疗。双重抗血小板治疗[阿司匹林加普拉格雷（Efient（®），第一三共株式会社英国分公司/礼来公司）、氯吡格雷或替格瑞洛（Brilique（®），阿斯利康）]是英国临床实践中的标准治疗方法。普拉格雷是本综述的重点。
本综述旨在评估普拉格雷在其经许可的用于PCI治疗ACS的适应症范围内的临床有效性和成本效益，是对英国国家卫生与临床优化研究所技术评估TA182的综述。
检索了四个电子数据库（MEDLINE、EMBASE、Cochrane图书馆、PubMed），从数据库建立至2013年6月检索随机对照试验（RCT），至2013年8月检索在接受PCI的ACS患者中比较普拉格雷与氯吡格雷或替格瑞洛的经济评估。
临床结局包括非致命和致命心血管（CV）事件、治疗不良反应以及健康相关生活质量（HRQoL）。成本效益结局包括每获得一个生命年的增量成本和每获得一个质量调整生命年（QALY）的增量成本。一个独立的经济模型评估了四个相互排斥的亚组：接受PCI治疗STEMI且患有和未患有糖尿病的ACS患者，以及接受PCI治疗UA或NSTEMI且患有和未患有糖尿病的ACS患者。
未发现TA182报告之外的新RCT。TRITON-TIMI 38（通过普拉格雷优化血小板抑制评估心肌梗死溶栓治疗38试验中的治疗结局改善）在计划接受PCI的ACS患者中比较了普拉格雷与氯吡格雷。未发现相关经济评估。我们的分析集中在一个关键患者亚组：年龄<75岁、体重>60 kg（既往无卒中或短暂性脑缺血发作）的患者。对于主要复合终点（CV原因死亡、非致命心肌梗死或非致命卒中），普拉格雷组（8.3%）发生的事件在统计学上显著少于氯吡格雷组（11%）。主要出血事件未观察到统计学显著差异。然而，当合并主要和次要出血事件时，氯吡格雷有显著优势（3.0%对3.9%）。关于HRQoL无法得出结论。敏感性分析结果证实，对于所有四个ACS亚组，在5至10年内，与氯吡格雷相比，在每获得一个QALY支付意愿阈值为20,000至30,000英镑的情况下，普拉格雷可能是一种具有成本效益的治疗选择。在整个40年时间范围内，所有估计值均<每获得一个QALY 10,000英镑。
缺乏数据妨碍了普拉格雷与替格瑞洛的临床比较；因此，普拉格雷与替格瑞洛相比的相对有效性仍然未知。长期建模练习容易受到关于早期健康结局获益持续的主要假设的影响。
本综述的一个关键优势在于，使用氯吡格雷的通用价格证明了普拉格雷与氯吡格雷相比的成本效益。尽管该报告证明了在每获得一个QALY支付意愿阈值为20,000至30,000英镑的情况下普拉格雷与氯吡格雷相比的成本效益，但长期建模容易受到关于长期获益的主要假设的影响。缺乏数据妨碍了普拉格雷与替格瑞洛的临床比较；因此，普拉格雷与替格瑞洛相比的相对有效性仍然未知。需要来自英国长期临床注册的经过充分审核的数据，该注册针对接受PCI治疗的特定ACS患者群体，这些患者接受普拉格雷、替格瑞洛和氯吡格雷治疗。
本研究注册为PROSPERO CRD42013005047。
英国国家卫生研究院卫生技术评估计划。
