Carefully Monitor Direct Oral Anticoagulant Medications

Direct oral anticoagulants (DOACs) have transformed anticoagulation management by offering fixed doses and less monitoring compared with warfarin. Although they do not require routine monitoring (ie, international normalized ratio [INR] testing every 4-6 weeks for patients on stable doses), certain clinical situations require additional steps to provide appropriate dosing and reduce the risk of complications.

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There are 4 available DOACs on the US market: apixaban (Eliquis; Bristol Myers Squibb, Pfizer), edoxaban (Savaysa; Daiichi-Sankyo), rivaroxaban (Xarelto; Johnson & Johnson), and dabigatran (Pradaxa; Boehringer Ingelheim). Although some of these medications have additional FDA-approved uses (ie, rivaroxaban to reduce the risk of thrombotic vascular events in patients with peripheral artery disease), all 4 DOACs are approved for the treatment and prevention of venous thromboembolism and stroke prevention in nonvalvular atrial fibrillation (AFib).^1-4

Apixaban, edoxaban, and rivaroxaban are oral direct factor Xa inhibitors due to their mechanism of action of selectively inhibiting factor Xa to reduce the generation of thrombin and thrombus formation. Dabigatran is a direct thrombin inhibitor because it targets and inhibits factor IIa (thrombin) to achieve the same clinical effect.^1-4

Because these medications reduce the blood’s ability to clot, they are effective for preventing and treating certain thromboembolic events.^1-4 However, they also impair the body’s ability to stop a bleed, making it crucial for patients to be aware of bleeding events (ie, epistaxis, hematemesis, and melena).^1-4 Due to their predictable pharmacokinetic and pharmacodynamic responses at fixed doses, DOACs obviate the routine monitoring necessary with warfarin, which requires frequent adjustments based on INR monitoring.5,6 Additionally, all DOACs carry a boxed warning that premature discontinuation can increase the risk of thrombotic events.^1-4

Laboratory Tests

The American Heart Association (AHA) recommends obtaining a complete blood count (CBC), comprehensive metabolic panel (CMP), and liver function tests (LFTs) before initiation of a DOAC.⁵ A CBC provides information on an individual’s hematologic status. Because DOACs increase the risk of bleeding, it is important to ensure a patient has normal platelet counts and hemoglobin levels before initiation. Low levels could indicate a potential bleed that could be worsened by continued DOAC therapy. These labs help establish a patient’s baseline values and provide health care providers with the necessary parameters to make decisions to adjust treatment as needed from the outset.^5,6

Hepatic Impairment

LFTs are obtained because DOACs are hepatically metabolized, and impaired liver function could affect the drug’s metabolism. Impairment could lead to increased drug exposure and bleeding risk.1-4 Assessing liver function before therapy initiation will determine whether any dose adjustments will be required (see Table 1).^{1-4, 7-10}

Table 1.

Renal Impairment

A CMP includes a serum creatinine, which is a key component in evaluating renal function via creatinine clearance because DOACs are renally eliminated, and renal impairment can lead to drug accumulation and an increased risk of bleeding.^1-4 This allows clinicians to determine whether adjustments or alternative anticoagulants may be more appropriate (see Table 2 and Table 3).^{1-4, 7-10}

Table 2.

Table 3.

Ongoing Monitoring

Although there is no universally established routine monitoring schedule for patients on DOACs, the AHA does recommend that these monitoring parameters be performed in all patients before initiation, 1 to 3 months after initiation, and every 6 to 12 months thereafter, or more frequently based on patient-specific characteristics.⁹ If a situation warrants measurement of DOAC levels, such as a major bleeding event or concern about drug accumulation, the preferred test to quantify the anticoagulant effects would be anti–factor Xa activity calibrated specifically for the DOAC being measured.^1-4 Although DOACs were designed to reduce the burden of regular testing, meaningful and ongoing assessment ensures safety and efficacy.

REFERENCES

1. Rivaroxaban. MedlinePlus. Updated April 15, 2023. Accessed June 4, 2025. https://medlineplus.gov/druginfo/meds/a611049.html

2. Edoxaban. MedlinePlus. Updated June 15, 2020. Accessed June 4, 2025. https://medlineplus.gov/druginfo/meds/a614055.html

3. Apixaban. MedlinePlus. Updated February 15, 2025. Accessed June 4, 2025. https://medlineplus.gov/druginfo/meds/a613032.html

4. Dabigatran. MedlinePlus. Updated August 15, 2021. Accessed June 4, 2025. https://medlineplus.gov/druginfo/meds/a610024.html#:~:text=Dabigatran

5. Chen A, Stecker E, Warden BA. Direct oral anticoagulant use: a practical guide to common clinical challenges. J Am Heart Assoc. 2020;9(13):e017559. doi:10.1161/JAHA.120.017559

6. Dunois C. Laboratory monitoring of direct oral anticoagulants (DOACs). Biomedicines. 2021;9(5):445. doi:10.3390/biomedicines9050445

7. Xarelto. Prescribing information. Janssen Pharmaceuticals, Inc; 2021. Accessed June 4, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215859s000lbl.pdf

8. Eliquis. Prescribing information. Bristol Myers Squibb; 2012. Accessed June 4, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf

9. Savaysa. Prescribing information. Daiichi Sankyo, Inc; 2015. Accessed June 4, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf

10. Pradaxa. Prescribing information. Boehringer Ingelheim; 2011. Accessed June 4, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf