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Published on

15/7/2025

List of VKAs

VKAs are used in cases of atrial fibrillation (whether valvular or non-valvular). DOACs, on the other hand, are used specifically in cases of non-valvular atrial fibrillation.

List of VKAs: Understanding Vitamin K Antagonists, their Functioning and their Management

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

There are two main families of anticoagulants: injectables and oral medications. Oral anticoagulants are represented by two main classes: vitamin K antagonist oral anticoagulants (VKA) and direct-acting oral anticoagulants (DOAC). This article will focus specifically on vitamin K antagonists, their nature, their use, the precautions to be taken, and how they are managed, based on information provided by the sources.

Introduction to Oral Anticoagulants and Specifics of Vitamin K Antagonists

Oral anticoagulants are prescribed as tablets or capsules to be swallowed. Among them, antivitamin K drugs (AVK) 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 necessary.

Les sources distinguent clairement les AVK des anticoagulants oraux d’action directe (AOD). Les AVK sont utilisés en cas de fibrillation auriculaire (qu'elle soit valvulaire ou non valvulaire). Les AOD, en revanche, sont utilisés spécifiquement en cas de fibrillation auriculaire non valvulaire, lorsque celle-ci est associée à au moins un facteur de risque thromboembolique (correspondant à un score CHA2DS2-VASc ≥ 1 pour les hommes et ≥ 2 pour les femmes). Les facteurs de risque incluent un antécédent d'AVC, d'accident ischémique transitoire ou d'embolie systémique, une fraction d'éjection ventriculaire gauche < 40 %, une insuffisance cardiaque symptomatique de classe ≥ II de la NYHA, un âge ≥ 65 ans, le diabète, une coronaropathie ou une hypertension artérielle. Il est important de noter que les AOD n'ont pas démontré leur efficacité dans la fibrillation auriculaire liée à une pathologie valvulaire ni dans la prévention des thromboses de valve.

Anticoagulant treatment, whether with VKAs or AODs, is potentially dangerous if overdosed, with a risk of hemorrhage that can be fatal. For this reason, careful medical supervision is essential.

Vitamin K antagonists (VKAs) and Direct Oral Anticoagulants (DOACs) are considered first-line treatments when initiating oral anticoagulation. The choice between these two classes of anticoagulants should be made on a case-by-case basis.

Different Molecules of Vitamin K Antagonists

Depending on the source, there are two main classes of VKA:

Coumarin derivatives.
Indanedione derivatives.

In the class of coumarin derivatives, there is acenocoumarol, marketed under the names Sintrom® and Minisintrom®, and warfarin, known as Coumadine®. Warfarin is generally the most prescribed VKA in the rest of the world. In the class of indanedione derivatives, there is fluindione, marketed under the name Previscan®.

It is noteworthy that, in France, the prescription of fluindione represents nearly 70% of patients on vitamin K antagonists (VKA). However, sources indicate that a VKA from the coumarin family (warfarin or acenocoumarol) should be preferred if a VKA prescription is considered. Warfarin is the best-evaluated VKA. Fluindione should only be considered as a last resort. This recommendation is made in view of the risk of immuno-allergic reactions, often severe, which appear in 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 long-term fluindione (more than 6 months), who are well-balanced 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 any signs that may suggest an immuno-allergic adverse effect of cutaneous, hepatic or hematological type.

The list of oral vitamin K antagonist medications includes: COUMADINE, MINI-SINTROM, PRÉVISCAN, SINTROM.

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

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

Mechanism of Action and Indications of Vitamin K Antagonists (VKA)

Antivitamin K drugs work by partially blocking the activity of vitamin K. Vitamin K is an essential vitamin for blood coagulation. By blocking this activity, AVKs reduce the blood's ability to form clots.

VKAs are indicated for the prevention of thromboembolic events. This notably includes cases of atrial fibrillation, whether valvular or non-valvular. As mentioned previously, DOACs are limited to non-valvular atrial fibrillation.

Beyond atrial fibrillation, anticoagulant therapies, including vitamin K antagonists (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 circulation.

VKAs are particularly suitable when anticoagulant therapy is needed for a long duration, even for life. Generally, oral anticoagulant therapy (such as a VKA) is prescribed as a follow-up to injectable anticoagulant therapy (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 about ten days) and can be stopped when the oral treatment is balanced.

Classes and AVK drugs

There are two classes of VKAs:

The coumarin derivatives:
- Acenocoumarol (marketed under the names Sintrom® and Minisintrom®).
- Warfarin (marketed under the brand name Coumadine®).
The indanedione derivatives:
- Fluindione (marketed under the name Previscan®).

Most prescribed VKAs (Vitamin K antagonists)

Specifically, fluindione is prescribed very predominantly in France, representing nearly 70% of patients on VKAs. Globally, warfarin is generally the most prescribed VKA. It is noted that warfarin is the best evaluated VKA.

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

Main characteristics of VKAs

Efficacy and use: Demonstrated efficacy and long history of 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 measuring the INR (International Normalized Ratio). Regular monitoring of the INR is necessary in common practice. The dose is adjusted according to the target INR.
Antagonizing agents: Vitamin K and prothrombin complex concentrates (PCC) are used to antagonize the anticoagulant effect of vitamin K antagonists.
Half-life: Acenocoumarol: 8 h; Fluindione: 31 h; Warfarin: 35 to 45 h. The action of vitamin K antagonists (VKAs) is less sensitive to a missed dose than that of direct oral anticoagulants (DOACs) due to their longer half-life.
Hemorrhagic risk: AVKs, like DOACs, expose to a potentially serious risk of hemorrhage.
Precautions: Intramuscular injections are contraindicated in patients on VKAs. Be careful of falls and injuries that can 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 about taking a VKA. Carrying a card mentioning the treatment at all times is essential.

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

Monitoring of AVK Treatment: INR

A major and distinctive feature of VKA therapy, compared with AODs, is the need for regular biological monitoring of the degree of anticoagulation. This is done by measuring the INR (International Normalized Ratio).

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

Monitoring the degree of anticoagulation by measuring INR has a major advantage: the possibility of precisely monitoring the effectiveness of the treatment and adjusting the dose. However, it also has a disadvantage: the need for practical, routine, and regular monitoring for the patient and healthcare professionals. Unlike VKAs, there is no way to measure the degree of anticoagulation with DOACs, and routine hemostasis tests do not reflect their level of anticoagulation. For DOACs, there is no monitoring required in routine practice, which is an advantage, but the impossibility of monitoring despite questions about the variability of their plasma concentrations is a disadvantage.

The need for INR monitoring implies that patients on VKAs must have their INR measured at the rate indicated by their physician. They should also record the INR result and the daily dose taken since the previous INR in a logbook. Forgetting a blood test or the INR falling outside the acceptable range (too low or too high) are reasons to immediately notify their physician. It is important to note that the INR value may vary between two analysis laboratories, particularly in different countries, and it is advisable to check with your doctor if traveling.

The patient's ability to monitor the degree of anticoagulation for VKAs is a factor to consider when choosing between a VKA and a DOAC. In elderly patients, those of low weight, or those suffering from chronic renal failure, the use of VKAs allowing monitoring of the degree of anticoagulation is particularly indicated because these factors are in themselves risk factors for bleeding.

Risks, Drug and Food Interactions

Taking AVK medication exposes patients to certain dangers that require in-depth knowledge and constant vigilance. The main risk, a corollary of anticoagulation, is potentially serious hemorrhage.

Signs of Bleeding or Overdose: It is essential to know the signs of bleeding or overdose to avoid overlooking a potentially life-threatening situation. You should notify your doctor immediately if:

Your INR is outside the acceptable range (too low or too high).
Bleeding occurs, even if minor, such as bleeding from the gums, nose, eyes (red eye), blood in the urine, abnormally heavy periods, appearance of "bruises" (ecchymosis), black stools or stools covered in red blood, vomiting or bloody sputum, or a cut or injury that does not stop bleeding.
You experience unusual fatigue or paleness, abnormal shortness of breath, a headache that does not go away despite treatment, or malaise (these signs may indicate internal bleeding).

Drug Interactions: Vitamin K antagonists interact with numerous 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, whatsoever, without talking to your doctor.

Some substances are contraindicated with AVKs:

High-dose aspirin.
Medications containing miconazole (Daktarin oral gel, Gyno-Daktarin, Loramyc).
Medications containing St. John's wort (Arkogélules Millepertuis, Elusanes Millepertuis, MILDAC, PROSOFT), as they decrease the anticoagulant effect and expose to a risk of thrombosis.

Other substances are not recommended:

Low-dose aspirin.
Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, ketoprofen, diclofenac, etc.

Even paracetamol, although recommended as the painkiller of choice for patients on AVK, can be dangerous if taken in too high a dose.

These precautions apply not only to prescription or 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.
Eleuthero.
Kava.
Tonka bean.
White willow.
Other phytotherapy products.

Self-medication is therefore strictly prohibited when undergoing AVK treatment. As a safety measure, the introduction of a new medication by the physician is frequently accompanied by an INR measurement three or four days after the start of treatment to verify that the anticoagulant balance has not been disrupted.

Food Interactions: Certain foods contain high amounts of vitamin K and can alter the INR by blocking the action of AVKs. Examples include broccoli, lettuce, spinach, cabbage, cauliflower, Brussels sprouts. These foods are not prohibited, but it is crucial to distribute them regularly and without excess in the diet. The danger lies in the irregular consumption of these foods rich in vitamin K, which can lead to variations in INR. A balanced diet is generally recommended.

Alcohol: Alcohol consumption should be moderate.

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

Special situations and VKA treatment management

Living with AVK treatment means knowing how to manage a variety of specific situations, from day-to-day life to unforeseen events.

Missed Dose: If you forget to take your oral anticoagulant (VKA), the sources provide a precise course of action. You can take the missed dose if the omission is noted within eight hours after the usual time of administration. After this eight-hour period, it is preferable to skip this dose and take the next one at the usual time the next day. It is important to note this omission in your monitoring book and inform your doctor (and the laboratory, if the omission occurs shortly before a blood test). The half-lives of VKAs (8h for acenocoumarol, 31h for fluindione, 35-45h for warfarin) are generally longer than those of DOACs (8-15h for apixaban, 12-14h for dabigatran, 8-10h for edoxaban, 9-13h for rivaroxaban). The action of DOACs is very sensitive to forgetting a dose due to their shorter half-life, which is not the case with VKAs. Under no circumstances should the next dose be doubled to compensate 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 argument for replacing an effective and well-tolerated VKA treatment with a DOAC, and vice versa. However, if a change is decided, the transition methods are as follows:

De l'AVK à l'AOD : La première prise de l'AOD est possible sans délai lorsque l'INR est inférieur à un certain seuil : < 2 pour l'apixaban et le dabigatran, < 3 pour le rivaroxaban, et ≤ 2,5 pour l'edoxaban.
From DOAC to VKA: DOAC intake should be continued after the start of VKA therapy until the INR is ≥ 2. For dabigatran, the specific relay methods depend on the patient's renal function. As DOACs can interfere with INR measurement, the latter should be measured just before taking the medication, and again 24 hours after the last DOAC dose.

Surgical Intervention or Invasive Procedure: Any surgical intervention or invasive procedure in a patient on AVKs requires specific management to minimize the risk of bleeding. For minor procedures, an INR between 2 and 3 generally does not pose a problem. This includes cataract surgery, skin surgery, injections into joints (e.g., in cases of osteoarthritis), minor surgery of the mouth and teeth, or a digestive endoscopy.

For more extensive surgery, it is necessary to temporarily discontinue AVK treatment in order to return to an INR of less than 1.5, or even 1.2 for brain surgery. The sources do not explicitly detail "how" to stop and restart AVK in this context but mention temporary cessation.

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 is based on the use of heparin. In breastfeeding women, heparins and VKAs of the coumarin derivative family (warfarin, acenocoumarol) can be used. If you are taking VKAs and discover that you are pregnant or wish to become pregnant, you should inform your doctor.

Travel: When traveling, patients on 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 marketed in certain countries, such as France. In case of travel with significant time differences, ask your doctor for advice on adjusting the dosing schedule. As mentioned previously, be aware that the INR value may vary between laboratories, especially abroad, and check with your doctor.

Attention to Accidents and Falls: People taking oral anticoagulants (vitamin K antagonists) should be careful to protect themselves from anything that can cause significant bleeding or bruising. This includes avoiding violent sports or those with a high risk of falls or cuts. DIY activities, for example, can also present risks. Elderly people, who are more at risk of falling, should take steps to secure their homes. Any fall, especially on the head, or any blow to the head, should be the subject of a systematic medical consultation. In addition, the use of a soft toothbrush is recommended to avoid injuring the gums. It is advisable to use an electric shaver rather than a blade razor. Finally, it is preferable not to walk barefoot and not to remove corns or calluses from the feet yourself.

Treatment Choice and Initiation: When to Prescribe a VKA?

When oral anticoagulant therapy is initiated, a Vitamin K antagonist (VKA) or a Direct Oral Anticoagulant (DOAC) may be prescribed as first-line treatment. 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 renal function.
The predictable quality of the patient's treatment adherence.
The patient's ability to monitor the degree of anticoagulation by measuring INR (for VKAs).
The patient's preference, after receiving appropriate information on the different options.

Sources specifically emphasize that advanced age, low weight, and chronic renal insufficiency are factors that increase the risk of bleeding. In these situations, anticoagulation with VKAs is particularly indicated, precisely because it allows for monitoring of the degree of anticoagulation via the INR.

If the choice is a VKA, the sources recommend a VKA from the coumarin family, i.e. warfarin or acenocoumarol. Warfarin is specifically mentioned as the best-rated VKA. As detailed above, 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.

As fluindione is very widely prescribed in France, this recommendation is important for new initiations, while confirming that patients who are stable on long-term fluindione do not need to change treatment.

Pour l'initiation des AOD, il faut considérer leur élimination rénale et les modalités de prescription spécifiques à chaque molécule, incluant le nombre de prises, les critères de réduction de dose, les interactions médicamenteuses et les précautions d'emploi ou contre-indications. Le dabigatran est l'AOD le plus éliminé par voie rénale et le seul contre-indiqué en cas d'insuffisance rénale sévère (ClCr entre 15 et 29 ml/min). L'insuffisance rénale altère l'élimination rénale des AOD, augmentant leur taux plasmatique et le risque hémorragique. L'apixaban est recommandé à faible dose en cas d'insuffisance rénale sévère (ClCr 15-29 mL/min) et n'est pas recommandé en insuffisance rénale terminale (ClCr < 15 mL/min). Le dabigatran est contre-indiqué si la ClCr < 30 mL/min. Le rivaroxaban est recommandé à faible dose en cas d'insuffisance rénale modérée à sévère (ClCr 15-49 mL/min) et n'est pas recommandé en insuffisance rénale terminale (ClCr < 15 mL/min). L'edoxaban est recommandé à faible dose en cas d'insuffisance rénale modérée à sévère (ClCr 15-49 mL/min) et n'est pas recommandé en insuffisance rénale terminale (ClCr < 15 mL/min). Ces précisions sur les AOD sont pertinentes car la fonction rénale est un critère de choix important entre AVK et AOD.

Sources also mention that age and weight are factors influencing the dosage of DOACs, which contrasts with the adjusted dose of VKAs based on INR. For example, apixaban is 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 at a low dose (220 mg/day) in patients aged 80 years or older. Edoxaban is at a low dose (30 mg/day) in patients weighing ≤ 60 kg. Rivaroxaban can be used at a standard dose (20 mg/day) in patients older than 75 years and/or weighing less than 60 kg.

Daily life with VKA treatment: Compliance and safety

Once VKA therapy has been initiated, daily management by the patient is essential to guarantee its efficacy and safety. The importance of compliance is vital, and patients need to be reminded of this regularly. A regular dosing schedule is recommended.

Tools for Compliance and Safety: Several tools and practices are recommended to help the patient on VKA:

The permanent wearing of a card mentioning anticoagulant therapy. This document is a necessity. It must specify not to stop or modify the treatment and not to take any other treatment without consulting a healthcare professional. Such a card can be cut out from the supplied monitoring booklet.
The use of a follow-up sheet (or follow-up booklet) given to the patient. This sheet should detail the treatment (indication, start date, dosage, name and contact details of the prescriber, etc.), the dates of past and planned consultations, and the results of biological tests carried out, in particular the INR. The use of this document, to be presented to any healthcare personnel consulted, aims to ensure better coordination between healthcare providers (doctor, pharmacist, biologist, dentist, nurse, etc.). The patient must fill in this booklet each time blood is taken, noting the INR result and the daily dose taken. Any incident or missed dose should be noted.

Communication with Healthcare Professionals: It is essential that the patient reports that they are taking VKA medication to all healthcare professionals they consult. This includes physicians, pharmacists, analysis laboratories, nurses, dentists, physiotherapists, podiatrists, etc. This information is crucial because certain procedures are contraindicated or require precautions. For example, injections into the muscles are contraindicated in people taking VKAs. Before any injection, tooth extraction, foot care, minor surgery, or travel plans, the advice of the attending physician is essential. In case of bleeding, contacting your doctor quickly or going to the nearest emergency room is imperative.

Daily Precautions: Beyond medication management and medical follow-up, some simple precautions can reduce the risk of bleeding:

Take care to avoid injuries and bleeding, being cautious during physical or manual activities.
Use a soft toothbrush to protect gums.
Prefer an electric razor.
Do not walk barefoot.
Do not attempt to remove corns or calluses from your feet yourself.

Recognizing Warning Signs: As mentioned previously, knowledge of the signs of overdose or bleeding (abnormal bleeding, bruising, signs of internal bleeding such as unusual fatigue or pallor, persistent headaches, malaise) is vital.

Failure to comply with the prescribing instructions for oral anticoagulants (whether VKA or DOAC) exposes patients to an increased risk of thrombosis or hemorrhage. A "misuse" identified by the Haute Autorité de Santé includes intentional underdosing (aimed at reducing the risk of bleeding, a practice not proven to be effective or safe) and use outside of established recommendations (in patients without a significant thromboembolic risk factor or with valvular disease for DOACs). For VKAs, the dose should always be adjusted to the degree of anticoagulation, aiming for the recommended target INR. Anticoagulant treatment should be discussed on a case-by-case basis, especially in patients at low thromboembolic risk, considering individual characteristics, bleeding risk, and patient preferences.

In conclusion, antivitamin K drugs are old and effective oral anticoagulants used in a wide range of thromboembolic indications, including valvular atrial fibrillation. Their management requires close INR monitoring, regular follow-up, vigilance regarding drug and food interactions, and good patient compliance. Although new alternatives such as DOACs exist, VKAs remain an important choice, particularly for certain patient profiles, and their long-term use in stable patients is maintained. Open communication between the patient and healthcare professionals, as well as the use of monitoring tools, are fundamental for the safe and effective use of VKAs.