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

Abstract

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.

Systematic reviews of clinical practice guidelines: a methodological guide

“…This article was informed by insights gained through our experience in conducting SRs of CPGs at the University of Ottawa Heart Institute [50]. To provide further context to the reader, we summarize the processes used to complete an SR of CPGs on the outpatient use of low molecular weight heparin and fondaparinux for 10 indications of importance to Ontario decision-makers in Fig.…”

“…We caution reviewers, however, in interpreting or ''ranking'' the quality of recommendations strictly on the basis of the evidence used to inform them. Indeed, many clinically important recommendations are formed on the basis of very limited evidence and not every CPGR that has been informed by high-quality evidence will result in successful outcomes in every case [50].…”

Sedation Practices for Routine Gastrointestinal Endoscopy: A Systematic Review of Recommendations

“…In accordance with the AGREE II User Guide, 15 the study team prioritized the rigor of development domain; documents scoring ≥60% were considered to have appropriately addressed this domain. 16,17…”

Hypercoagulation and Viral Infection: Rationale of the Use of Anti-Thrombotic Therapies in Coronavirus-19 Disease

“…This occurs in a neutralization of Factor Xa, which ultimately inhibits the formation of thrombin and the formation of thrombus. Fondaparinux is also indicated in the prophylaxis and treatment of venous thrombo-embolism (26).…”