Keeping it simple: Single drug approaches to VTE treatment

Patient case: Selecting a regimen for DVT treatment

Consider the needs of the following patient:

Mathilde is 79 years old and lives by herself in a small village. She takes a short walk to the village shop most days and otherwise keeps herself busy at home
She considers herself lucky to have kept her independence. Some of her family live locally and she has good neighbours who can help her if she needs them
Mathilde is generally in good health. She is borderline obese (BMI 29 kg/m²) and receives an ACE inhibitor to reduce her blood pressure, but she has no history of major health problems; something Mathilde attributes to never smoking or drinking alcohol
But last week, she was bedridden for several days because of a urinary tract infection. After treatment with antibiotics, she recovered, but soon after she began to notice pain and swelling in her right leg
Her GP referred her to the local hospital where an ultrasound scan confirmed that she had a proximal deep vein thrombosis (DVT)
Mathilde stayed in hospital overnight and was given an interim dose of enoxaparin. She made it very clear that she does not like injections, and she is adamant that she will not need any extra visits from family or healthcare workers when she is discharged

What should you consider when choosing a DVT treatment for Mathilde?

What are the options for acute treatment of DVT?

The non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) are named as first-line treatments for DVT in patients without cancer by both the European Society of Cardiology (ESC) and the American College of Chest Physicians (ACCP).1,2

Anticoagulation is recommended for at least 3 months, but NOAC regimens differ the most during the first weeks of treatment – a time when recurrence risk is at its highest.1-3

The approved regimens for dabigatran and edoxaban include a mandatory phase of at least 5 days of treatment with a parenteral anticoagulant before administration of the oral drug can commence.4,5

In contrast, rivaroxaban and apixaban are single-drug, oral therapies that avoid the need for parenteral treatment.6,7

But these two treatments also differ in the acute phase. For apixaban, intensified dosing is administered for the first 7 days.7 On the other hand, patients receive intensified dosing of rivaroxaban for 21 days based on data showing that this provides equivalent thrombus regression to pretreatment with parental anticoagulation followed by a vitamin K antagonist.6,8

Approved NOAC doses for the treatment of VTE in patients with CrCl ≥15 ml/min4-7

*In patients with moderate (CrCl30–49 ml/min) or severe (CrCl15– 29 ml/min) renal impairment, a reduction of rivaroxaban dose from 20 mg once daily to 15 mg once daily should be considered if the patient’s assessed risk for bleeding outweighs the risk for recurrent DVT and PE;

^#Dabigatran 110 bid in patients aged ≥80 years or taking concomitant verapramil. In patients aged 75–80 years, patients with moderate renal impairment, patients with gastritis, oesophagitis or gastro-oesophagal reflux, or other patients at increased bleeding should receive dabigatran 150 mg bid or 110 mg bid based on an individual assessment of the thromboembolic risk and the risk of bleeding;
^‡Edoxaban 30 mg od in patients with one or more of moderate or severe renal impairment (creatinine clearance 15–50 mL/min), body weight ≤60 kg, or concomitant use of ciclosporin or dronedarone, erythromycin or ketoconazole.

Neither the ESC nor the ACCP recommend one NOAC over another. However, the ACCP do provide guidance on factors that may influence the choice of anticoagulant.1,2

One such factor is an avoidance of parenteral therapy. So, for a patient like Mathilde who is averse to injections, rivaroxaban or apixaban may be the best choice.2

Another factor to consider is dosing schedule and if once-daily dosing is preferred, rivaroxaban would then be selected over apixaban.2

Should anticoagulation be continued beyond 3 months?

Another important treatment decision would need to be made after 3 months.

The ACCP recommend continuing anticoagulation after 3 months for patients with a first unprovoked venous thromboembolism (VTE) and low or moderate bleeding risk, and cessation of anticoagulation after 3 months for patients with VTE provoked by surgery or non-surgical transient risk factors.2 The ESC recommend an individualized approach that takes into account the risk of recurrence versus the risk of bleeding.1

Assessment of a patient’s risk of recurrent VTE or bleeding determines whether anticoagulation is continued beyond 3 months1,2

In Mathilde’s case, it could be that the DVT was provoked by the short period of time that she was bedridden, but could that be a coincidence? Both her age and her BMI may increase the risk of recurrent VTE and it is also necessary to understand exactly how mobile she is in her day-to-day life.9

Further information on optimizing the duration of anticoagulation can be found here.

Summary

As always with decisions to anticoagulate, the benefits and risks of each treatment regimen must be well understood. The only way to do this, is to get to know the patient and consider them as an individual.

Because every patient is different.

Mathilde’s preference to avoid daily injections means that a parenteral treatment may not be suitable. However, other patients may be reassured by having family members or healthcare professionals visiting to administer their treatment, despite the burden that comes with injections.

As well as patient preference, factors such as comorbidities and the likelihood of treatment compliance need to be considered when choosing a regimen.

Only by taking everything into account is it possible to ensure that patients get the treatment that is right for them.

References

Mazzolai L, Aboyans V, Ageno W et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function. Eur Heart J 2018;39:4208–4218. Return to content
Kearon C., Akl E.A., Ornelas J. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149(2):315-52. Return to content
Limone B.L., Hernandez A.V., Michalak D. eta/. Timing of recurrent venous thromboembolism early after the index event: a meta-analysis of randomized controlled trials. Thromb Res. 2013; 132(4):420-426. Limone B.L., Hernandez A.V., Michalak D. eta/. Timing of recurrent venous thromboembolism early after the index event: a meta-analysis of randomized controlled trials. Thromb Res. 2013; 132(4):420-426. Return to content
Daiichi Sankyo Europe GmbH. Lixiana® (edoxaban) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf.[accessed 9 April 2020]. Daiichi Sankyo Europe GmbH. Lixiana® (edoxaban) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf.[accessed 9 April 2020]. Return to content
Boehringer Ingelheim International GmbH. Pradaxa® (dabigatran etexilate) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf [accessed 9 April 2020]. Boehringer Ingelheim International GmbH. Pradaxa® (dabigatran etexilate) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf [accessed 9 April 2020]. Return to content
Bayer AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf. [accessed 9 April 2020]. Bayer AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf. [accessed 9 April 2020]. Return to content
Bristol-Myers Squibb, Pfizer. Eliquis® (apixaban) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf. [accessed 9 April 2020]. Bristol-Myers Squibb, Pfizer. Eliquis® (apixaban) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf. [accessed 9 April 2020]. Return to content
Agnelli G, Gallus A, Goldhaber SZ et al. Treatment of proximal deep-vein thrombosis with the oral direct Factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in patients with acute symptomatic Deep-Vein Thrombosis) study. Circulation 2007;116:180–187. Return to content
Engbers MJ, van Hylckama Vlieg A, Rosendaal FR. Venous thrombosis in the elderly: incidence, risk factors and risk groups. J Thromb Haemost 2010;8:2105–2112. Return to content

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See Also

Keeping it simple: Single drug approaches to VTE treatment

Patient case: Selecting a regimen for DVT treatment

What are the options for acute treatment of DVT?

Should anticoagulation be continued beyond 3 months?

Summary

References

Join more than 1.500 of your peers to stay up to date with the latest in thrombosis.

Thrombosis Adviser

Join more than 1.500 of your peers to stay up to date with the latest in thrombosis.

See Also

Keeping it simple: Single drug approaches to VTE treatment

Patient case: Selecting a regimen for DVT treatment

What are the options for acute treatment of DVT?

Should anticoagulation be continued beyond 3 months?

Summary

References

See Also

See Also

See Also

See Also

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