Unfractionated heparin in cardiology: redefining the standard of practice.

Acute coronary syndromes (ACS) consist of unstable angina (UA), non-ST-segment myocardial infarction (NSTEMI) and ST-segment myocardial infarction (STEMI). Timely intervention with effective, predictable antithrombin therapy is critically important in the early management of these conditions. Platelet aggregation is also an important component of thrombus formation in arterial thrombosis. Historically, unfractionated heparin (UFH) has been combined with aspirin to suppress thrombin propagation and fibrin formation; however, its effectiveness has been questioned in this setting. Unlike newer anticoagulant alternatives, UFH paradoxically stimulates platelet aggregation, which may further promote clot formation. In addition, obtaining a valid therapeutic activated partial thromboplastin time (aPTT) in cardiology patients is a major challenge, and dosing is complex. Due to substantial variation in reagents and instruments, target aPTT ranges for UFH in ACS clinical trials cannot be extrapolated to individual institutions. Further, the risk of ischemic events is greater shortly after abrupt discontinuation of UFH compared with alternative agents with longer half-lives and less stimulation of platelet aggregation. Key UA-NSTEMI clinical trials have demonstrated that UFH is inferior to newer agents, such as the low-molecular-weight heparins (LMWHs). Consistent with this evidence, the most recent practice guidelines of the American College of Cardiology and the American Heart Association in UA-NSTEMI identify the LMWH enoxaparin as the agent of choice. In patients with STEMI receiving the fibrinolytic tenecteplase as reperfusion therapy, enoxaparin has also been superior to UFH in combination. In percutaneous procedures, newer indirect (enoxaparin) and direct (bivalirudin) antithrombins have demonstrated safety and efficacy. There is little doubt that as we move forward in optimizing adjunctive anticoagulation in the cardiology setting, UFH will largely be replaced by better antithrombin agents.

Venous thromboembolism prevention with LMWHs in medical and orthopedic surgery patients.

OBJECTIVE: To discuss the role of low-molecular-weight heparins (LMWHs) in the prevention of venous thromboembolism (VTE) in medical and orthopedic surgery patients. VTE prophylaxis trials in these practice settings establishing the current use of LMWHs marketed in the US are included. An overview is also provided of VTE incidence, risk factors, and prophylaxis consensus guidelines. DATA SOURCES AND STUDY SELECTION: Clinical trials, review articles, and meta-analyses for Food and Drug Administration-approved LMWHs were identified from a MEDLINE search (1980-March 2002). Search terms included dalteparin, enoxaparin, internal medicine, low-molecular-weight heparin, orthopedic surgery, risk factors, tinzaparin, and venous thromboembolism. DATA SYNTHESIS: Consensus guidelines are useful as an initial guide to appropriate VTE prophylaxis; however, a review of the primary literature is needed to identify optimal agents, regimens, or interventions. LMWHs have demonstrated sound efficacy in VTE prevention; however, the quantity and quality of literature are not always comparable for the available agents. CONCLUSIONS: Enoxaparin has demonstrated efficacy and safety in VTE prevention in medical patients, whereas information is limited or lacking for dalteparin and tinzaparin. Total hip replacement (THR) trials have been conducted with all US-marketed LMWHs and have demonstrated the efficacy and safety of each agent. Trials specifically establishing the efficacy of an LMWH in total knee replacement surgery (TKR) have been published for enoxaparin. One combination THR and TKR trial has been published for tinzaparin. These trial outcomes have positioned the LMWHs as key alternatives to adjusted-dose warfarin for VTE prophylaxis in orthopedic surgery. Inherent differences between LMWHs prevent the extrapolation of clinical outcomes from 1 trial to another.