Intensive Care Unit, Hospital General Universitario de Elche, Elche, Spain.
Pharmacoeconomics. 2012 Apr;30(4):303-21. doi: 10.2165/11589290-000000000-00000.
The benefit of unfractionated heparin (UFH) added to aspirin in patients with acute coronary syndromes (ACS) was described more than 20 years ago. Ever since, a wide variety of anticoagulant drugs have become available for clinical use, including low-molecular-weight heparins (LMWH), direct thrombin inhibitors and selective factor Xa inhibitors.
The aim of this study was to critically review the available evidence on the cost and incremental cost effectiveness of anticoagulants in patients with ACS.
Studies were identified using specialist databases (UK NHS Economic Evaluation Database [NHS EED] and Cost-Effectiveness Analysis [CEA] Registry), PubMed and the reference lists of recovered articles. Only studies based on randomized controlled trials were considered for inclusion. Finally, 22 studies were included in the review.
Enoxaparin is the only LMWH that has been shown to reduce the risk of death or myocardial infarction in patients with non-ST-elevation ACS (NSTE-ACS). In economic studies based on the ESSENCE trial conducted in the late 1990s, enoxaparin was consistently associated with a lower risk of coronary events, a reduction in the number of revascularization procedures and a lower cost per patient than UFH. However, these results refer to patients managed conservatively, with little use of thienopyridines and glycoprotein IIb/IIIa inhibitors, and the results are difficult to extrapolate to moderate-to-high-risk patients managed with the present day early invasive strategy. Available studies of LMWH in ACS with persistent elevation of ST-segment (STE-ACS) are limited to patients treated with thrombolysis. In this scenario, enoxaparin was shown to be a dominant alternative compared with UFH in a study based on the ASSENT-3 study and was considered an economically attractive alternative in three studies based on the ExTRACT-TIMI 25 study. However, these results should be interpreted cautiously due to the heterogeneity of the supportive randomized trials and the possible underestimation of bleeding costs. The effectiveness and safety of bivalirudin, a direct thrombin inhibitor, were evaluated in the ACUITY study (NSTE-ACS patients managed invasively) and the HORIZONS-AMI study (STE acute myocardial infarction patients planned for primary percutaneous coronary intervention). Bivalirudin monotherapy was not inferior to heparin plus a glycoprotein IIb/IIIa inhibitor and reduced the risk of major bleeding. The economic evaluations based on these studies suggest that bivalirudin is an attractive alternative to heparin plus a glycoprotein-IIb/IIIa inhibitor. In the OASIS-5 trial, compared with enoxaparin, fondaparinux reduced the mortality in patients with NSTE-ACS, probably because of a reduced risk of bleeding. In three economic evaluations of fondaparinux versus enoxaparin based on this trial, fondaparinux was the dominant strategy in two of them, and still economically attractive in a third. Taken as a whole, the usefulness of economic studies of anticoagulants in patients with ACS is undermined by the quality of the evidence about their effectiveness and safety; the narrow spectrum of the analysed scenarios; the lack of economic evaluations based on systematic reviews; the limitations of sensitivity analyses reported by the available economic evaluations; and their substantial risk of commercial bias.
The available studies suggest that enoxaparin is an economically attractive alternative compared with UFH in patients with NSTE-ACS treated conservatively and STE-ACS patients treated with thrombolysis. Bivalirudin in patients with ACS treated invasively is cost effective compared with heparin plus a glycoprotein IIb/IIIa inhibitor. In patients with NSTE-ACS, fondaparinux is cost effective compared with enoxaparin. The usefulness of these results for decision making in contemporary clinical practice is limited due to problems of internal and external validity.
二十多年前，曾描述过在急性冠状动脉综合征（ACS）患者中联合应用未分级肝素（UFH）和阿司匹林的益处。从那时起，已经有多种抗凝药物可供临床使用，包括低分子量肝素（LMWH）、直接凝血酶抑制剂和选择性因子 Xa 抑制剂。
本研究旨在批判性地回顾 ACS 患者中抗凝剂的成本和增量成本效益的现有证据。
使用专业数据库（英国国家医疗服务体系经济评价数据库[ NHS EED ]和成本效益分析[ CEA ]登记处）、PubMed 和检索到的文章的参考文献列表来确定研究。仅考虑基于随机对照试验的研究。最终，有 22 项研究被纳入综述。
依诺肝素是唯一一种被证明可以降低非 ST 段抬高型 ACS（NSTE-ACS）患者死亡或心肌梗死风险的 LMWH。在 90 年代后期进行的 ESSENCE 试验的经济研究中，依诺肝素与 UFH 相比，始终与较低的冠状动脉事件风险、较少的血运重建术和每位患者的较低成本相关。然而，这些结果指的是接受保守治疗的患者，很少使用噻吩吡啶类和糖蛋白 IIb/IIIa 抑制剂，并且结果难以外推到接受目前早期侵入性策略治疗的中高危患者。关于 ACS 中持续 ST 段抬高（STE-ACS）的 LMWH 的现有研究仅限于接受溶栓治疗的患者。在基于 ASSENT-3 研究的研究中，依诺肝素与 UFH 相比被证明是一种占主导地位的替代方案，在基于 EXTRACT-TIMI 25 研究的三项研究中被认为是一种具有经济吸引力的替代方案。然而，由于支持性随机试验的异质性和出血成本可能被低估，这些结果应谨慎解释。直接凝血酶抑制剂比伐卢定在 ACUITY 研究（接受侵入性治疗的 NSTE-ACS 患者）和 HORIZONS-AMI 研究（计划接受直接经皮冠状动脉介入治疗的 STE 急性心肌梗死患者）中进行了评估。与肝素加糖蛋白 IIb/IIIa 抑制剂联合应用相比，比伐卢定单药治疗并不劣于肝素加糖蛋白 IIb/IIIa 抑制剂，并降低了大出血风险。基于这些研究的经济评估表明，比伐卢定是肝素加糖蛋白 IIb/IIIa 抑制剂的一种有吸引力的替代方案。在 OASIS-5 试验中，与依诺肝素相比，磺达肝癸钠降低了 NSTE-ACS 患者的死亡率，可能是因为出血风险降低。在基于该试验的磺达肝癸钠与依诺肝素的三项经济评估中，磺达肝癸钠在其中两项中是主导策略，在第三项中仍然具有经济吸引力。总的来说，由于其有效性和安全性证据的质量、分析情景的狭窄范围、缺乏基于系统评价的经济评估、现有经济评估报告的敏感性分析的局限性以及其商业偏见的实质性风险，抗凝剂在 ACS 患者中的经济研究的有用性受到了损害。
现有研究表明，与 UFH 相比，依诺肝素在接受保守治疗的 NSTE-ACS 患者和接受溶栓治疗的 STE-ACS 患者中具有经济吸引力。在接受侵入性治疗的 ACS 患者中，比伐卢定与肝素加糖蛋白 IIb/IIIa 抑制剂相比具有成本效益。在 NSTE-ACS 患者中，磺达肝癸钠与依诺肝素相比具有成本效益。由于存在内部和外部有效性问题，这些结果对当代临床实践中的决策制定的有用性有限。
