A systematic review of clinical practice guidelines on the use of low molecular weight heparin and fondaparinux for the treatment and prevention of venous thromboembolism: Implications for research and policy decision-making

BackgroundVenous thromboembolism (VTE) is a major global cause of morbidity and mortality. Low molecular weight heparin (LMWH) and fondaparinux (FDP) are frequently used to treat and prevent VTE and have a variety of safety and practical advantages over other anticoagulants, including use in outpatient settings. These medications are commonly listed on drug formularies, which act as a gateway for health plan prescription coverage by outlining the circumstances under which patients will be covered for specific drugs and drug products. Because patient access to medications is impacted by the nature of their listing on formularies, they must be rigorously reviewed and modernized as new evidence emerges.MethodsAs part of a broader drug class review team, we completed a systematic review of clinical practice guidelines to determine whether the recommendations they reported aligned with the indications listed for the coverage of LMWH and FDP in an outpatient drug formulary. Guideline quality was assessed using the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool. Recommendation matrices were used to systematically compare, categorize, and summarize included recommendations.ResultsTwenty-seven guidelines were included from which 168 eligible recommendations were identified. Generally, AGREE II domains were adequately addressed; however, domain five (applicability) was poorly addressed. Most recommendations were based on moderate- to low-quality/limited evidence and reported on the use of LMWHs generally; few reported on specific agents.ConclusionsOur findings contributed to the recommendation that the formulary listing for LMWH and FDP be streamlined to include coverage for specific outpatient indications. The paucity of available evidence on the comparative efficacy of specific LMWH agents against each other and FDP limited agent-specific listing recommendations, highlighting the need for high-quality comparative studies on this topic.

研究背景
静脉血栓栓塞症（Venous thromboembolism, VTE）是全球范围内导致发病与死亡的主要病因之一。低分子肝素（Low molecular weight heparin, LMWH）与磺达肝癸钠（fondaparinux, FDP）是治疗和预防静脉血栓栓塞症的常用药物，相较于其他抗凝药物，二者具备多项安全性与临床应用优势，包括可用于门诊诊疗场景。此类药物通常被纳入药物处方集，处方集作为健康保险计划覆盖处方药物的准入依据，明确了患者可获得特定药物或药品报销的适用情形。由于患者的药物可及性受其在处方集中的收录情况影响，因此当新的临床证据出现时，必须对处方集进行严格评估与更新。
研究方法
作为更广泛的药物类别审查团队的一部分，我们完成了一项针对临床实践指南的系统综述，旨在明确指南中提出的推荐意见是否与门诊药物处方集内低分子肝素和磺达肝癸钠的报销适应证相契合。采用指南研究与评价工具（Appraisal of Guidelines for Research & Evaluation II, AGREE II）对纳入指南的质量进行评估。通过推荐意见矩阵系统地对纳入的推荐意见进行比较、分类与总结。
研究结果
共纳入27篇指南，从中筛选出168条符合标准的推荐意见。总体而言，AGREE II的各评价维度均得到了适当覆盖，但第五维度（适用性）的评估结果欠佳。大部分推荐意见基于中低质量或有限的临床证据，且多笼统提及低分子肝素的使用，仅少数推荐意见针对具体药物品种。
研究结论
本研究结果支持一项推荐意见，即应简化低分子肝素与磺达肝癸钠的处方集收录规则，将特定门诊适应证纳入报销范围。目前针对不同低分子肝素品种之间以及低分子肝素与磺达肝癸钠的相对疗效的相关研究证据匮乏，限制了针对具体药物品种的收录推荐意见制定，这凸显了开展高质量相关比较研究的必要性。