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  • Indications
  • Treatment of DVT

Acenocoumarol in Treatment of DVT

The use of acenocoumarol in the treatment of symptomatic deep vein thrombosis (DVT) is well-established. Acenocoumarol was shown to be superior to warfarin in efficacy and was effective in cases of warfarin resistance.51,52

  • Efficacy and Safety
  • Clinical Evaluation
  • Therapeutic Efficacy

Efficacy and safety of various vitamin K antagonists for the treatment of symptomatic venous thromboembolism
Lensing AWA, Hematology Meeting Reports 2008; 2(1): 11-12.

4289 patients with symptomatic venous thromboembolism

Randomized, comparative study

The patients were randomly allocated to receive one of the oral anticoagulants within 72 hours of the episode – warfarin, acenocoumarol, phenprocoumon or fluindione. The dose was adjusted to achieve a target international normalized ratio (INR) of 2.0–3.0 and the treatment was continued for 3 months.

The 3-month incidence of recurrent venous thromboembolism and of major bleeding.

  • The incidence of recurrent venous thromboembolism was lower with acenocoumarol, phenprocoumon and fluindione compared to warfarin.
  • The safety of the 4 drugs was comparable.
  • The frequency of INR monitoring was similar for all the 4 drugs.

VTE, venous thromboembolic events.

Clinical evaluation of acenocoumarol, an anticoagulant of intermediate range
Rullo FR et al., JAMA, 1958; 168(6):743-747.

Acenocoumarol, an orally administered anticoagulant with intermediate duration of effect, was used in the treatment of 100 hospitalized patients, majorly venous thromboembolism. The treatment was tailored to keep the prothrombin time (PT) between 20 and 43 seconds. The average initial dose of acenocoumarol was 21 mg. The average maintenance dose was 6.6 mg per day.

It was observed that in over one-third of the patients the PT was within the clinically practical range after 18 hours of dosing. The drug was thus rapidly effective. The dose of the drug was easy to adjust. Side-effects were few; no gastrointestinal intolerance was seen, and only five patients had minor bleeding episodes. Some patients continued to receive anticoagulant therapy on an ambulant basis after leaving the hospital, and one continued it for 64 days.

This experience illustrated some significant advantages of acenocoumarol, especially the possibility of controlling the intensity of its effects and the time of their disappearance.

Therapeutic efficacy of acenocoumarol in a warfarin-resistant patient with deep venous thrombosis: A case report
Marusic S et al., Eur J Clin Pharmacol 2009; 65(12): 1265-66.

  • What is warfarin resistance? Warfarin dose requirements of >70 mg weekly in order to maintain the international normalized ratio (INR) in the target therapeutic range is called warfarin resistance.
  • The case: An 80-year-old man with idiopathic iliofemoral vein thrombosis was admitted to the hospital. He had a history of hypertension and congestive cardiac failure for which he was receiving lisinopril 20 mg daily and furosemide 40 mg daily.
  • Treatment for venous thrombosis: Low-molecular weight heparin was administered on admission. Warfarin was added on the second day of admission at a loading dose of 6 mg daily.
  • Observations: The INR increased from 0.97 at baseline to 1.41 on day 15 despite increasing the dose of warfarin to 21 mg daily.
  • Action taken: Warfarin was stopped and acenocoumarol was started at a daily dose of 8 mg 5 days later.
  • The response: The target INR value of 2.66 was achieved after 2 doses of acenocoumarol.
  • Follow-up: At 9 months of follow-up, the patient is still stable with an INR between 2.0–3.0 with a daily dose of 2 mg acenocoumarol.
  • What is the cause for warfarin resistance? All other parameters remaining the same, the only cause for warfarin resistance is possibly genetic (CYP2C9 polymorphism).
Recommendations for oral anticoagulant (OAC) therapy in deep vein thrombosis (DVT) are as follows53:
  1. For patients with a first episode of DVT secondary to a reversible risk factor, long-term treatment with vitamin K antagonists (VKAs) for 3 months is recommended (Grade 1A)
  2. For patients with a first episode of idiopathic DVT, treatment with VKAs for at least 6 to 12 months is recommended (Grade 1A).
  3. For patients with DVT and cancer, low-molecular weight heparin is recommended for the first 3 to 6 months of long-term anticoagulant therapy (Grade 1A). For these patients, anticoagulation is recommended indefinitely or until the cancer is resolved.
  4. For patients with a first episode of DVT and documented antiphospholipid syndrome or who have two or more thrombophilic risk factors (e.g. combined factor V Leiden and prothrombin 20210 gene mutations), treatment for 12 months is recommended (Grade 1C). Indefinite anticoagulant therapy is also recommended in these patients.
  5. For patients with a first episode of DVT who have documented deficiency of antithrombin, protein C or protein S, or the factor V Leiden or prothrombin 20210 gene mutation, homocysteinemia, or high factor VIII levels (>90th percentile), treatment for 6 to 12 months is recommended (Grade 1A). Indefinite therapy is recommended, as for patients with idiopathic thrombosis (Grade 2C).
  6. For patients with two or more episodes of objectively documented DVT, indefinite treatment is suggested (Grade 2A).
  7. It is recommended that the VKA dose be adjusted to maintain a target international normalized ratio (INR) of 2.5 (2.0–3.0) for all treatment durations (Grade 1A). The guidelines recommend against high-intensity VKA therapy (3.1–4.0) (Grade 1A) and against low-intensity therapy (INR range, 1.5–1.9) compared to INR range of 2.0 to 3.0 (Grade 1A).
  8. In patients who receive indefinite anticoagulant treatment, the risk‐benefit of continuing such treatment should be reassessed at periodic intervals (Grade 1C).
  9. Repeat testing with Doppler ultrasound is suggested to exclude residual thrombosis or measurement of plasma D-dimers, to help determine the duration of the treatment (Grade 2C).