490: Update! Anticoagulation for Venous Thromboembolism with Dr. Tara Lech, PharmD

July 7, 2025 | By Ben Furman

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Transcript available via YouTube

Master the latest approaches for treating venous thromboembolism with expert tips on direct oral anticoagulant (DOAC) selection, dosing, and duration. Learn how to tailor anticoagulation for special populations, handle treatment failures, and navigate long-distance travel risks. We’re joined by Dr. Tara Lech, PharmD, CACP (Beth Israel Lahey Health, @AnticoagPharmD, @anticoagpharmd.bsky.social‬).

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Show Segments

• Intro
• Case 1 from Kashlak
• Choosing the right anticoagulant
• Distal deep vein thrombosis management
• Anticoagulation in special populations
• Case 2 from Kashlak
• Understanding treatment failure
• Anticoagulation reversal agents
• Outro

Disclosures

Dr. Lech reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Anticoagulation for Venous Thromboembolism (VTE) Pearls

1. Apixaban is preferred over rivaroxaban in patients with impaired renal function (CrCl <50 mL/min), especially <30 mL/min, due to better safety data.
2. Direct oral anticoagulants (DOACs) should be avoided in patients taking strong enzyme inducers or inhibitors like carbamazepine, rifampin, or ketoconazole; these patients require warfarin.
3. A 3-month course of anticoagulation is sufficient for venous thromboembolism (VTE) provoked by a transient risk factor (e.g., surgery, estrogen therapy); however, patients remain at increased risk of recurrence.

4. Compression stockings are not recommended for VTE prevention during air travel in low-risk individuals, but may benefit high-risk patients (e.g., prior VTE, cancer); prophylactic low-dose anticoagulation for high-risk patients is best decided on a case-by-case basis.
5. Avoid unnecessary hypercoagulable workups after unprovoked VTE; instead, focus on age-appropriate cancer screenings unless there’s a clear indication for the additional testing.
6. If treatment failure is suspected, check a Xa level or D-dimer to assess for adherence or clot extension, and consider switching to low molecular weight heparin (LMWH) if failure is confirmed.

Anticoagulation for VTE Update with Dr. Tara Lech – Notes

Initial Choice of Anticoagulant

The choice of anticoagulant in venous thromboembolism (VTE) management hinges on factors like renal function, bleeding risk, medication interactions, and insurance status. Most patients can be treated with a direct oral anticoagulant (DOAC). For patients with impaired renal function (creatinine clearance <50 mL/min and especially <30 mL/min), apixaban is preferred over rivaroxaban due to better safety data (Lau et al., 2022).

Note: Rivaroxaban and apixaban are the preferred DOAC agents when compared to dabigatran because of higher rates of GI side effects and dyspepsia with dabigatran (Lau et al., 2022)

Evidence supports that DOACs are as safe as warfarin in patients with chronic kidney disease, with no dose adjustment needed for apixaban in VTE treatment even with renal impairment (Buller et al., 2012; Cohen et al., 2022). There is still uncertainty regarding rivaroxaban dosing in patients with renal failure. 

While DOACs have fewer drug-drug interactions than other anticoagulants like warfarin, significant interactions still exist. For patients on carbamazepine, ketoconazole, and rifampin, DOACs should be avoided. These patients require a bridge to warfarin (Wiggins et al., 2020). Also, while not a true drug-drug interaction, patients should be encouraged to use acetaminophen instead of NSAIDs while on DOACs.

Starter pack dosing

Both apixaban (10mg BID for 7 days) and rivaroxaban (15 mg BID for 21 days) have increased dosing in the acute phase of VTE treatment, as patients are hypercoagulable and thus more likely to clot again (Stevens et al., 2021). Our expert recommends giving the full starter pack dosing at discharge, regardless of inpatient DOAC dosing, to minimize confusion. However, our expert also emphasizes that these decisions must be made on a case-by-case basis. If a patient has a high risk of bleeding or has been on a longer (i.e., 5-10 days) of parenteral therapy, then starting them on maintenance dosing upon discharge is appropriate.

Treatment duration

Treatment duration is based on whether the provoking factor is transient (i.e., recent surgery, estrogen therapy, etc.,) or persistent (malignancy, antiphospholipid antibody syndrome, etc). 

• Transient risk factors: treat with 3 months of a DOAC, while recognizing that the lifetime risk of recurrence never truly returns to zero.
• Persistent risk factors: often require indefinite anticoagulation.

Typically, follow-up ultrasounds at the end of the acute treatment period to monitor clot burden are not needed. Of note, complete clot resolution can take up to a year.

Anticoagulation and Air Travel

Evidence is mixed, but general recommendations to reduce risk of VTE in those at increased risk include frequent ambulation, calf exercises, compression stockings, and aisle seating with upcoming long travel (>6 hours) (Khan et al., 2012). For individuals with no increased risk for VTE, compression stockings are not recommended

For high-risk patients, prophylactic dosing options recommended by our expert include:

• Apixaban 2.5 mg BID
• Rivaroxaban 10 mg once daily

Case-by-case evaluation is crucial, including consideration of access to healthcare at the destination.

Distal Deep Vein Thrombosis (DVT) Management

A distal DVT is a thrombosis of the deep vein(s) of the calf that does not reach the popliteal vein (Chopard et al., 2020). Management can be guided by patient preference and symptoms. For minimally symptomatic patients who prefer not to be on anticoagulation, serial ultrasounds over two weeks without anticoagulation are an option (Stevens et al., 2021). However, many patients favor anticoagulation to reduce the risk of clot propagation.

VTE Treatment in Special Populations

Conception, Pregnancy and Breastfeeding

• Women of childbearing age being treated for a VTE should routinely be asked about pregnancy plans, as many treatment options for VTE are either known teratogens (warfarin) or lack sufficient safety data in pregnancy (DOACs). 
• If not transitioned during conception, transition from DOACs or warfarin to low molecular weight heparin (LMWH) when a pregnancy is identified.
• During breastfeeding, safety data for DOACs is  insufficient, so LMWH is also recommended.

People with Cancer 

• Historically, treatment with LMWH was gold standard, but studies (Agnelli et al., 2020) support DOAC safety and efficacy.
• Avoid warfarin, as its use is associated with a higher bleeding rate (Meyer et al., 2002).
• A recent study, the API-CAT trial (Mahé et al., 2025)  suggested that Apixaban 2.5 mg BID has similar safety as 5 mg BID with less bleeding, however this is pending further verification.

Low and High BMI

• Low BMI: Less robust data, but apixaban appears comparable to warfarin (Tan et al., 2024).
• High BMI (>40): Previously, there was cautious use of DOACs in patients with high BMIs due to limited evidence but newer data and guidelines support DOAC use in patients who are obese (Martin et al., 2021). Our expert advises caution post-bariatric surgery, as DOAC absorption may be impaired; monitoring anti-Xa levels may be helpful.

Differences between DOACs

While guidelines do not recommend one DOAC over another, there are some notable differences between DOACs to keep in mind.

• Renal Clearance: Apixaban (~25%) < Rivaroxaban (~33%) < Dabigatran (~80%) (Yao et al., 2020).
• GI Bleeding: Higher risk with rivaroxaban and edoxaban compared to apixaban (Sandblad et al., 2023; Jin et al., 2021; Lau et al., 2022).
• Administration: Rivaroxaban must be taken with food—important for people with cancer who have nausea or anorexia.

What to do About Unprovoked VTE?

Initial 3-6 months of anticoagulation is standard. If no provoking risk factor is identified during that initial time period, start conversations about indefinite therapy.

Reminder: A hypercoagulable workup should be avoided unless clinically indicated (e.g., renal artery thrombosis, cerebral venous sinus thrombosis,  family history, etc.,). Importantly, thrombophilia rarely impacts clinical decisions for VTE treatment (Connors, 2017), and unnecessary maintenance of anticoagulation therapy places patients at a needlessly elevated bleeding risk (Middledorp et al., 2023).  Instead, prioritize age-appropriate cancer screenings. For more discussion on the hypercoagulable workup, refer to our past episode with Dr. Jean Connors!

What to do about Treatment Failure?

It’s important to note that anticoagulation is not clot lysis. Anticoagulants inhibit the coagulation cascade, which prevents clot propagation, while allowing native fibrinolytic systems to dissolve the thrombus. Symptoms from VTE can persist for months even with adequate treatment. If you have suspicion for treatment failure, it’s important to uncover what might be causing the failure. Assess for medication adherence. DOACs can be challenging medications to take! If you worry about treatment adherence, it is reasonable to check a Xa level. A D-dimer can be another tool. If the D-dimer level is low, it’s likely that symptoms are caused by residual clot; however, if it is elevated, there may be a new or extended clot. Ultimately, if treatment failure is suspected, a follow up ultrasound should be performed. Importantly, it is critical to have the follow up ultrasound read by the same radiologist that performed the initial study. 

In the case of true treatment failure, treatment escalation is required (Rodger et al., 2019):

• If on DOAC, switch to therapeutic LMWH for 4 weeks.
• If on LMWH, consider a 20-25% dose increase.

If treatment failure is confirmed, it’s a great idea to reach out to pharmacist colleagues for guidance!

Reversal of DOACs

Four-factor prothrombin complex concentrate is the reversal agent of choice for warfarin and can be used for DOAC reversal as well. Andexanet alfa is a newer, DOAC-specific agent but there are ongoing studies to delineate its utility given the increased risk of thromboembolic events associated with its use. Full FDA approval remains pending for some indications.

**Update 24 December 2025: Andexanet alfa has been pulled from the US market by AstraZeneca. It was initially given accelerated approval in 2018 with the stipulation that randomized trials for safety and clinical efficacy were needed. The ANNEXA-I trial (Connolly, 2024) found increased risk of thrombosis and on 22 December 2025 the FDA put out an update on the safety of andexanet alfa (FDA site, accessed 24 December 2025)**

Links

AC Forum 

Goal

Listeners will develop a framework for outpatient management of venous thromboembolic disease. 

Learning objectives

1. Identify the initial management steps for a patient with a first-time, unprovoked deep vein thrombosis, including the selection criteria for direct oral anticoagulants
2. Review the current evidence regarding the optimal duration of anticoagulation therapy for venous thromboembolism (VTE), including considerations for extended treatment in patients with persistent risk factors
3. Differentiate the management strategies for anticoagulation in specific patient populations

Citation

Furman BW, Lech T, Williams PN, Watto MF. “490 Anticoagulation for Venous Thromboembolism Update”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast July 7, 2025.