Publié le

7/5/2026

List of AVKs

Vitamin K antagonists (VKAs) are used in cases of atrial fibrillation (whether valvular or non-valvular). Direct oral anticoagulants (DOACs), on the other hand, are used specifically in cases of non-valvular atrial fibrillation.

List of Vitamin K Antagonists: Understanding Vitamin K Antagonists, How They Work, and How They Are Managed

Anticoagulant treatments play a crucial role in the prevention and management of diseases related to blood clot formation. These medications, often referred to as "blood thinners," aim to prevent the formation of clots (thrombosis) in blood vessels, thus preventing serious events such as pulmonary or cerebral embolism. The obstruction of a vein by a clot is called a thromboembolic event. In France, in 2013, it was estimated that 3.12 million patients were receiving at least one anticoagulant, including 1.49 million on an oral anticoagulant.

There are two main types of anticoagulants: injectable and oral.

Oral anticoagulants are represented by two main classes: vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). This article will focus specifically on vitamin K antagonists, their nature, use, precautions, and management, based on information provided by various sources. Introduction to Oral Anticoagulants and Specifics of VKAs: Oral anticoagulants are prescribed in tablet or capsule form. Among them, vitamin K antagonists (VKAs) are the most common and the oldest. They are used in the treatment or prevention of thromboembolic events when long-term, or even lifelong, anticoagulant therapy is required. Sources clearly distinguish VKAs from direct oral anticoagulants (DOACs). Vitamin K antagonists (VKAs) are used to treat atrial fibrillation (whether valvular or non-valvular). Direct oral anticoagulants (DOACs), on the other hand, are specifically used for non-valvular atrial fibrillation when it is associated with at least one thromboembolic risk factor (corresponding to a CHA2DS2-VASc score ≥ 1 for men and ≥ 2 for women). Risk factors include a history of stroke, transient ischemic attack, or systemic embolism; a left ventricular ejection fraction < 40%; symptomatic heart failure of NYHA class ≥ II; age ≥ 65 years; diabetes; coronary artery disease; or hypertension. It is important to note that DOACs have not demonstrated efficacy in atrial fibrillation related to valvular disease or in the prevention of valve thrombosis. Anticoagulant therapy, whether with VKAs or DOACs, is potentially dangerous in case of overdose and presents a risk of bleeding, sometimes fatal. For this reason, close medical monitoring is essential. VKAs and DOACs are considered first-line treatments when initiating oral anticoagulation. The choice between these two families of anticoagulants must be made on a case-by-case basis.

The Different Molecules of Vitamin K Antagonists

According to the According to sources, two main classes of vitamin K antagonists (VKAs) are distinguished: Coumarin derivatives and indanedione derivatives. Within the coumarin derivative class, we find acenocoumarol, marketed under the names Sintrom® and Minisintrom®, and warfarin, known as Coumadin®. Warfarin is generally the most prescribed VKA worldwide. In the indanedione derivative class, we find fluindione, marketed under the name Previscan®. It is noteworthy that, in France, fluindione accounts for nearly 70% of VKA prescriptions. However, sources indicate that a vitamin K antagonist (VKA) from the coumarin family (warfarin or acenocoumarol) should be preferred if VKA therapy is being considered. Warfarin is the best-evaluated VKA. Fluindione should only be considered as a last resort. This recommendation is based on the risk of often severe immuno-allergic reactions that appear within the first 6 months of treatment and are more frequently observed with fluindione than with other VKAs. Despite this warning for new prescriptions, in patients treated with fluindione long-term (more than 6 months), who are well-controlled and tolerate the treatment well, there is no reason to change the treatment. For patients who have recently started treatment with fluindione, regular monitoring of renal function is necessary, as well as for any signs that may suggest an immune-allergic adverse reaction of a cutaneous, hepatic, or hematological type.

The list of orally available vitamin K antagonists includes: COUMADIN, MINI-SINTROM, PREVISCAN, SINTROM.

The half-lives of the VKAs mentioned in the sources are:

Acenocoumarol: 8 h
Fluindione: 31 h
Warfarin: 35 to 45 h

Mechanism of Action and Indications of VKAs

Vitamin K antagonists work by partially blocking the activity of vitamin K. Vitamin K is an essential vitamin for blood clotting. By blocking this activity, vitamin K antagonists (VKAs) reduce the blood's ability to form clots. VKAs are indicated for the prevention of thromboembolic events. This includes, in particular, cases of atrial fibrillation, whether valvular or non-valvular. As mentioned previously, direct oral anticoagulants (DOACs) are limited to non-valvular atrial fibrillation. Beyond atrial fibrillation, anticoagulant therapies, including VKAs when long-term treatment is required, are prescribed in various situations to prevent or treat thrombosis and embolism. These situations include:

Phlebitis (inflammation of a vein with clot formation).
Pulmonary or cerebral embolism.
Certain myocardial infarctions.
In people with certain heart rhythm disorders that can promote clot formation.
In people with an artificial heart valve.
In people who are temporarily immobilized (for example, after a leg fracture or surgery) to prevent clot formation due to slowed blood flow.

VKAs are particularly suitable when anticoagulant therapy is needed for a long time, or even for life. Generally, oral anticoagulant therapy (such as a VKA) is prescribed following treatment with an injectable anticoagulant (such as heparin). The effect of oral anticoagulants is gradual, reaching its maximum after a few days. Heparin injections are therefore maintained for a few days (often around ten days) and can be stopped when the oral treatment is stabilized.

Classes and medications of Vitamin K Antagonists (VKAs)

There are two classes of VKAs:

Coumarin derivatives:
- Acenocoumarol (marketed under the names Sintrom® and Minisintrom®).
- Warfarin (marketed under the name Coumadin®).
Indanedione derivatives:
- Fluindione (marketed under the name Previscan®).

Most Prescribed Vitamin K Antagonists

Unusually, fluindione is the most frequently prescribed vitamin K antagonist in France, representing nearly 70% of patients on vitamin K antagonists. Globally, warfarin is the most commonly prescribed vitamin K antagonist. It should be noted that warfarin is the best-evaluated vitamin K antagonist.

The use of fluindione should only be considered as a last resort due to the risk of often severe immuno-allergic reactions. However, in patients treated with fluindione long-term (more than 6 months), who are well-controlled and well-tolerated, there is no reason to modify the treatment.

Main Characteristics of Vitamin K Antagonists

Efficacy and Use: Proven efficacy and long-standing use.
Interactions: Numerous drug and food interactions. Self-medication is strongly discouraged. It is essential to consult your doctor before taking any new medication, dietary supplement, herbal product, or before an injection or procedure.
Monitoring: The degree of anticoagulation is measured by the INR (International Normalized Ratio). Regular INR monitoring is necessary in routine practice. The dose is adjusted according to the target INR.
Antagonist agents: Vitamin K and prothrombin complex concentrates (PCCs) are used to antagonize the anticoagulant effect of vitamin K antagonists (VKAs).
Half-life: Acenocoumarol: 8 h; Fluindione: 31 h; Warfarin: 35 to 45 h. The action of vitamin K antagonists (VKAs) is less sensitive to missed doses than that of direct oral anticoagulants (DOACs) due to their longer half-life.
Hemorrhagic risk: VKAs, like DOACs, carry a risk of potentially serious bleeding.
Precautions: Injections into muscles are contraindicated in patients taking VKAs. Be careful of falls and injuries that could cause bleeding. It is recommended to use a soft toothbrush and an electric razor.

It is crucial to adhere to the prescribed dose, the frequency of INR measurements, and to inform all healthcare professionals that you are taking a VKA. Carrying a card indicating your treatment at all times is essential.

The use of VKAs is contraindicated during pregnancy and breastfeeding. During pregnancy, anticoagulation relies on the use of heparin. In breastfeeding women, heparins and vitamin K antagonists (VKAs) from the coumarin derivative family (warfarin, acenocoumarol) can be used.

Monitoring of Vitamin K Antagonist (VKA) Therapy: INR

A major and distinctive characteristic of VKA therapy, compared to DOACs, is the need for regular biological monitoring of the degree of anticoagulation. This monitoring is performed by measuring the INR (International Normalized Ratio).

The INR is a standardized measure of the time it takes for blood to clot. The VKA dose is adjusted according to the INR value, the goal being to reach a "target INR" determined by the doctor.

Monitoring the degree of anticoagulation by measuring the INR has a major advantage: the possibility of precisely tracking the effectiveness of the treatment and adjusting the dose. However, it also has a disadvantage: the need for routine and regular practical monitoring by both the patient and healthcare professionals. Unlike vitamin K antagonists (VKAs), there is no way to measure the degree of anticoagulation with direct oral anticoagulants (DOACs), and routine hemostasis tests do not reflect their anticoagulation level. For DOACs, no monitoring is necessary in routine practice, which is an advantage, but the inability to monitor them despite concerns about the variability of their plasma concentrations is a disadvantage. The need for INR monitoring means that patients on VKAs must have their INR measured at the intervals prescribed by their doctor. They must also record the INR result and the daily dose taken since the previous INR measurement in a logbook. Missing a blood test or an INR falling outside the acceptable range (too low or too high) are reasons to immediately notify their doctor. It is important to note that INR values can vary between two testing laboratories, particularly in different countries, and it is advisable to consult your doctor before traveling. The patient's ability to monitor the degree of anticoagulation with vitamin K antagonists (VKAs) is a factor to consider when choosing between a VKA and a direct oral anticoagulant (DOAC). In elderly patients, those with low body weight, or those suffering from chronic renal insufficiency, the use of VKAs that allow for monitoring of the degree of anticoagulation is particularly indicated, as these factors are themselves risk factors for bleeding. Risks, Drug and Food Interactions: Taking VKA therapy exposes you to certain risks that require thorough knowledge and constant vigilance. The main risk, a corollary of anticoagulation, is potentially serious bleeding. Signs of Bleeding or Overdose: It is essential to know the signs of bleeding or overdose to avoid missing a potentially life-threatening situation. You must inform your doctor immediately if:

Your INR falls outside the acceptable range (too low or too high).
You experience any bleeding, even minor, such as bleeding gums, nosebleeds, bleeding eyes (red eye), blood in the urine, abnormally heavy periods, the appearance of bruises, black or bright red stools, vomiting or coughing up blood, or a cut or wound that will not stop bleeding.
You experience unusual fatigue or paleness, abnormal shortness of breath, a headache that does not go away despite treatment, or general malaise (these signs may indicate internal bleeding).

Drug Interactions: Vitamin K antagonists interact with a wide variety of substances. These interactions can either increase the risk of bleeding or decrease the anticoagulant effect and increase the risk of thrombosis. For this reason, it is essential to NEVER take any medication, whatever it may be, without consulting your doctor.

Some substances are contraindicated with vitamin K antagonists (VKAs):

High-dose aspirin.
Medications containing miconazole (Daktarin oral gel, Gyno-Daktarin, Loramyc).
Medications containing St. John's wort (Arkogélules St. John's wort, Elusanes St. John's wort, MILDAC, PROSOFT), because they reduce the anticoagulant effect and increase the risk of thrombosis.

Other substances are not recommended:

Low-dose aspirin.

Even paracetamol, although recommended as the pain reliever of choice for patients on vitamin K antagonists (VKAs), can be dangerous if taken in too high a dose.

These precautions apply not only to prescription and over-the-counter medications, but also to dietary supplements and herbal products (phytotherapy). Many natural ingredients can increase the risk of bleeding:

Omega-3 fatty acids (fish oils, for example).
Garlic.
Turmeric.
Ginger.
Ginkgo.
Ginseng.
Eleutherococcus.
Kava.
Tonka bean.
White willow.
Other herbal products.

Self-medication is therefore absolutely prohibited when taking vitamin K antagonists (VKAs). As a safety precaution, when a doctor introduces a new medication, they often measure the INR three or four days after starting treatment to check that the anticoagulant balance has not been disrupted. Food Interactions: Some foods contain high amounts of vitamin K and can alter the INR by blocking the action of vitamin K antagonists (VKAs). Examples include broccoli, lettuce, spinach, cabbage, cauliflower, and Brussels sprouts. These foods are not forbidden, but it is crucial to include them in your diet regularly and in moderation. The danger lies in the irregular consumption of these vitamin K-rich foods, which can lead to fluctuations in the INR. A balanced diet is generally recommended.

Alcohol: Alcohol consumption should be moderate.

VKAs have many drug and food interactions, while DOACs have fewer.

Specific Situations and Management of VKA Treatment

Living with VKA treatment involves knowing how to manage various specific situations, from everyday life to unexpected events.

Missing a Dose: If you forget to take your oral anticoagulant (VKA) medication, the sources provide specific instructions. You can take the missed dose if you realize you missed it within eight hours of the usual time. After this eight-hour period, it is best to skip that dose and take the next one at the usual time the following day. It is important to note this missed dose in your treatment log and inform your doctor (and the laboratory, if the missed dose occurs shortly before a blood test). The half-lives of vitamin K antagonists (VKAs) (8 hours for acenocoumarol, 31 hours for fluindione, 35-45 hours for warfarin) are generally longer than those of direct oral anticoagulants (DOACs) (8-15 hours for apixaban, 12-14 hours for dabigatran, 8-10 hours for edoxaban, 9-13 hours for rivaroxaban). The effect of DOACs is very sensitive to missed doses due to their shorter half-life, which is not the case with VKAs. Under no circumstances should the next dose be doubled to make up for a missed dose, whether for VKAs or DOACs.

Switching from a VKA to a DOAC (and vice versa): Sources indicate that there is no scientific evidence to support replacing an effective and well-tolerated VKA treatment with a DOAC, and vice versa. However, if a change is decided upon, the switching procedures are as follows:

From VKA to DOAC: The first dose of the DOAC can be taken without delay when the INR is below a certain threshold: < 2 for apixaban and dabigatran, < 3 for rivaroxaban, and ≤ 2.5 for edoxaban.
From DOAC to VKA: DOAC treatment should be continued after starting VKA therapy until the INR is ≥ 2. For dabigatran, the specific switching method depends on the patient's renal function. Since DOACs can interfere with INR measurement, the INR should be measured just before taking the medication, and then again 24 hours after the last DOAC dose.

Surgical Intervention or Invasive Procedure: Any surgical intervention or invasive procedure in a patient on VKA requires specific management to minimize the risk of bleeding. For minor procedures, an INR between 2 and 3 is generally not a problem. This includes cataract surgery, skin surgery, injections into the joints (for example, in cases of osteoarthritis), minor oral and dental surgery, or a digestive endoscopy. For more complex surgery, it is necessary to temporarily stop VKA treatment to achieve an INR below 1.5, or even 1.2 for brain surgery. The sources do not explicitly detail how to stop and restart VKA in this context, but they do mention the temporary discontinuation. Pregnancy and Breastfeeding: The use of VKAs is contraindicated during pregnancy and breastfeeding. There are other types of anticoagulant treatments that the doctor can prescribe if necessary. Anticoagulation in pregnant women relies on the use of heparin. In breastfeeding women, heparins and vitamin K antagonists (VKAs) from the coumarin derivative family (warfarin, acenocoumarol) can be used. If you are taking VKAs and discover you are pregnant or planning to become pregnant, you must inform your doctor. Travel: When traveling, patients taking VKAs should take certain precautions. It is advisable to bring your prescription, a sufficient quantity of medication, and your monitoring booklet. This is particularly important because some VKAs may only be available in certain countries, such as France. If you are traveling with a significant time difference, ask your doctor for advice on adjusting your dosing schedule. As mentioned previously, be aware that INR values can vary between laboratories, especially abroad, and consult your doctor. Beware of Accidents and Falls: People taking oral anticoagulants (AVK) should be careful to protect themselves from anything that could cause significant bleeding or bruising. This includes avoiding contact sports or activities with a high risk of falls or cuts. DIY activities, for example, can also be risky. Older people, who are more at risk of falls, should take steps to make their homes safer. Any fall, especially on the head, or any blow to the head, should prompt a medical consultation. In addition, using a soft-bristled toothbrush is recommended to avoid injuring the gums. It is advisable to use an electric razor rather than a blade razor. Finally, it is best not to walk barefoot and not to remove corns or calluses from the feet yourself.

Choice and Initiation of Treatment: When to Prescribe a VKA?

When oral anticoagulant treatment is initiated, a VKA or a DOAC may be prescribed as first-line therapy. The choice between these two classes is not universal and must be made on a case-by-case basis. Several factors are taken into account by the physician to guide this decision:

The patient's individual bleeding risk.
The patient's age and weight.
The patient's kidney function.
The patient's anticipated level of adherence to treatment.
The patient's ability to monitor the degree of anticoagulation by measuring INR (for vitamin K antagonists).
The patient's preference, after receiving appropriate information on the different options.

Sources specifically emphasize that advanced age, low weight, and chronic kidney disease are factors that increase the risk of bleeding. In these situations, anticoagulation with vitamin K antagonists (VKAs) is particularly indicated, precisely because it allows monitoring of the degree of anticoagulation via the INR. If a VKA is chosen, sources recommend favoring a VKA from the coumarin family, i.e., warfarin or acenocoumarol. Warfarin is specifically mentioned as the best-evaluated VKA. As detailed previously, fluindione should only be considered as a last resort for new prescriptions, due to the increased risk of severe immuno-allergic reactions, particularly during the first 6 months. Since fluindione is the most widely prescribed drug in France, this recommendation is important for new initiations, while confirming that patients stable on long-term fluindione do not need to change treatment. For initiating DOACs, renal elimination and the specific prescribing guidelines for each molecule must be considered, including the number of doses, dose reduction criteria, drug interactions, and precautions for use or contraindications. Dabigatran is the DOAC most readily eliminated renally and the only one contraindicated in cases of severe renal impairment (creatinine clearance between 15 and 29 ml/min). Renal impairment impairs the renal elimination of DOACs, increasing their plasma concentration and the risk of bleeding. Apixaban is recommended at a low dose for severe renal impairment (CrCl 15-29 mL/min) and is not recommended for end-stage renal disease (CrCl < 15 mL/min). Dabigatran is contraindicated if CrCl < 30 mL/min. Rivaroxaban is recommended at a low dose for moderate to severe renal impairment (CrCl 15-49 mL/min) and is not recommended for end-stage renal disease (CrCl < 15 mL/min). Edoxaban is recommended at a low dose for moderate to severe renal impairment (CrCl 15-49 mL/min) and is not recommended for end-stage renal disease (CrCl < 15 mL/min). These details about DOACs are relevant because renal function is an important criterion for choosing between VKAs and DOACs. Sources also mention that age and weight are factors influencing DOAC dosage, which contrasts with the INR-based dose adjustment of VKAs. For example, apixaban is prescribed at a low dose (5 mg/day) if the patient has at least two of the following characteristics: age ≥ 80 years, weight ≤ 60 kg, serum creatinine ≥ 1.5 mg/dL. Dabigatran is prescribed at a low dose (220 mg/day) in patients aged 80 years or older. Edoxaban is prescribed at a low dose (30 mg/day) in patients weighing ≤ 60 kg. Rivaroxaban can be used at the standard dose (20 mg/day) in patients over 75 years of age and/or weighing less than 60 kg.

Living Daily with Vitamin K Antagonist Therapy: Adherence and Safety

Once vitamin K antagonist therapy is initiated, daily management by the patient is essential to ensure its effectiveness and safety. The importance of adherence to treatment is vital and must be regularly emphasized to the patient. A regular dosing schedule is advised.

Tools for Adherence and Safety: Several tools and practices are recommended to help patients on vitamin K antagonists:

Carrying a card indicating anticoagulant treatment at all times. This document is mandatory. It must specify not to stop or modify the treatment and not to take any other medication without consulting a healthcare professional. Such a card can be cut from the provided monitoring booklet. The use of a monitoring sheet (or monitoring booklet) given to the patient. This sheet should detail the treatment (indication, start date, dosage, name and contact information of the prescriber, etc.), the dates of past and planned consultations, and the results of laboratory tests performed, particularly the INR. The use of this document, to be presented to any healthcare professional consulted, aims to ensure better coordination between caregivers (doctor, pharmacist, biologist, dentist, nurse, etc.). The patient must complete this booklet at each blood test, noting the INR result and the daily dose taken. Any missed or missed doses must be recorded.

Communication with Healthcare Professionals: It is essential that the patient informs all healthcare professionals they consult that they are taking vitamin K antagonists (VKAs). This includes doctors, pharmacists, laboratories, nurses, dentists, physiotherapists, podiatrists, etc. This information is crucial because some procedures are contraindicated or require precautions. For example, injections into muscles are contraindicated in people taking VKAs. Before any injection, tooth extraction, foot care, minor surgery, or travel plans, the treating physician's advice is essential. En cas de saignement, contacter rapidement son médecin ou se rendre aux urgences les plus proches est impératif.

Précautions Quotidiennes : Au-delà de la gestion des médicaments et du suivi médical, certaines précautions simples peuvent réduire le risque d'hémorragie:

Faire attention pour éviter les blessures et les saignements, en étant prudent lors d'activités physiques ou manuelles.
Utiliser une brosse à dents souple pour protéger les gencives.
Préférer un rasoir électrique.
Ne pas marcher pieds nus.
Ne pas tenter de retirer soi-même les cors ou durillons des pieds.

Reconnaître les Signes d'Alerte : Comme mentionné précédemment, la connaissance des signes de surdosage ou de saignement (saignements anormaux, ecchymoses, signes de saignement interne comme fatigue ou pâleur inhabituelle, maux de tête persistants, malaise) est vitale.

Le non-respect des modalités de prescription des anticoagulants oraux (qu'il s'agisse d'AVK ou d'AOD) expose les patients à une augmentation du risque thrombotique ou hémorragique. Un "mésusage" identifié par la Haute Autorité de santé inclut les sous-dosages intentionnels (visant à réduire le risque de saignement, une pratique non démontrée comme efficace ou sûre) et l'utilisation en dehors des recommandations établies (chez des patients sans facteur de risque thrombo-embolique significatif ou avec une maladie valvulaire pour les AOD). Pour les AVK, la dose doit toujours être adaptée au degré d'anticoagulation, en visant l'INR cible recommandé. Le traitement anticoagulant doit être discuté au cas par cas, surtout chez les patients à faible risque thrombo-embolique, en considérant les caractéristiques individuelles, le risque hémorragique et les préférences du patient.

En conclusion, les antivitamines K sont des médicaments anticoagulants oraux anciens et efficaces, utilisés dans une large gamme d'indications thromboemboliques, y compris la fibrillation auriculaire valvulaire. Leur gestion nécessite une surveillance étroite de l'INR, un suivi régulier, une grande vigilance concernant les interactions médicamenteuses et alimentaires, et une bonne observance du patient. Bien que de nouvelles alternatives comme les AOD existent, les AVK restent un choix important, notamment pour certains profils de patients, et leur utilisation au long cours chez des patients stables est maintenue. Une communication ouverte entre le patient et les professionnels de santé, ainsi que l'utilisation des outils de suivi, sont fondamentales pour une utilisation sûre et efficace des AVK.