Is enoxaparin (Low Molecular Weight Heparin) still required as Venous Thromboembolism (VTE) prophylaxis for patients on aspirin and clopidogrel (Plavix)?

From the Guidelines

Yes, enoxaparin for VTE prophylaxis is still generally required for hospitalized patients at risk for venous thromboembolism, even if they are already taking aspirin and clopidogrel. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel primarily prevents arterial thrombosis but provides inadequate protection against venous thromboembolism 1. Enoxaparin, a low molecular weight heparin, works through a different mechanism by inhibiting factor Xa and thrombin, making it effective for preventing venous clots. The standard prophylactic dose is typically enoxaparin 40mg subcutaneously once daily (or 30mg twice daily in some cases), adjusted for renal function and weight.

Some key points to consider when using enoxaparin for VTE prophylaxis include:

• Renal function: dose adjustments may be necessary for patients with compromised renal function, with a recommended dose of 30 mg of subcutaneous enoxaparin daily for VTE prophylaxis and 1 mg/kg subcutaneously every 24 hours for VTE treatment for patients with creatinine clearance less than 30 mL/min 1.
• Weight: obese patients may require a higher dose of enoxaparin, such as 60 mg once daily, to achieve target range of thromboprophylaxis without increased bleeding 1.
• Bleeding risk: using enoxaparin alongside DAPT does increase bleeding risk, so individual patient assessment is crucial, with particular caution in patients with active bleeding, severe thrombocytopenia, or recent intracranial hemorrhage.

The decision to use enoxaparin for VTE prophylaxis should balance the patient's VTE risk factors (immobility, surgery, cancer, prior VTE) against bleeding risk. For patients with very high bleeding risk, mechanical prophylaxis with sequential compression devices might be considered as an alternative 1. Overall, the use of enoxaparin for VTE prophylaxis in hospitalized patients at risk for venous thromboembolism is supported by recent guidelines and studies, including the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

From the Research

Venous Thromboembolism Prophylaxis

The use of enoxaparin as VTE prophylaxis for patients on aspirin and clopidogrel is a topic of interest.

• The study 2 analyzed the effectiveness and safety of thromboprophylaxis with enoxaparin in medical inpatients, but it does not specifically address the use of enoxaparin in patients on aspirin and clopidogrel.
• Another study 3 investigated the efficacy and safety profile of commonly used VTE prophylaxis agents following hip and knee arthroplasty, and found that aspirin, enoxaparin, and dabigatran have an overall satisfactory efficacy and safety profile.
• However, the study 4 discusses anticoagulation during and after acute coronary syndrome, and mentions that dual antiplatelet therapy composed of aspirin plus a third generation P2Y12 inhibitor is the gold standard, while aspirin plus second generation P2Y12 inhibitor (clopidogrel) may be used as an alternative.
• The study 5 compared rates of VTE using different anticoagulants in anticoagulation-naïve patients being discharged home after total knee arthroplasty, and found that there is a decreased risk of VTE with LMWH, XaI, and fondaparinux compared to ASA.

Enoxaparin Use in Specific Patient Groups

• The study 6 performed a post-hoc analysis of two randomized studies to compare efficacy, safety, and overall survival of fondaparinux to standard initial (low-molecular-weight) heparin (LMWH) treatment in cancer patients with venous thromboembolism, and found that fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients.
• However, there is no direct evidence to suggest that enoxaparin is still required as VTE prophylaxis for patients on aspirin and clopidogrel, as the studies do not specifically address this patient population.

Considerations for VTE Prophylaxis

• The choice of pharmacologic prophylaxis should be made based on a balance of the risk/benefit profile of each medication 5.
• The use of enoxaparin as VTE prophylaxis may be considered in certain patient groups, but the decision should be based on individual patient factors and the specific clinical context.