Published on

May 7, 2026

List of AVKs

Vitamin K antagonists (VKAs) are used to treat atrial fibrillation (whether valvular or non-valvular). Direct oral anticoagulants (DOACs), on the other hand, are used specifically to treat 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, thereby preventing serious events such as pulmonary or cerebral embolism. The blockage 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 sources, there are two main classes of vitamin K antagonists (VKAs): 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-studied VKA. Fluindione should only be considered as a last resort. This recommendation is based on the risk of often severe immuno-allergic reactions that occur within the first 6 months of treatment and are observed more frequently with fluindione than with other VKAs. Despite this warning regarding 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 nature.

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

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

Acenocoumarol: 8 a.m.
Fluindione: 31 hours
Warfarin: 35 to 45 hours

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 accompanied by clot formation).
Pulmonary or cerebral embolism.
Certain heart attacks.
In people with certain heart rhythm disorders that can lead to blood clot formation.
In people with an artificial heart valve.
In people who are temporarily immobilized (for example, after a broken leg or surgery) to prevent blood clots caused by reduced 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 peak after a few days. Heparin injections are therefore continued for a few days (often around ten days) and can be discontinued once the oral treatment has stabilized.

Classes and medications of Vitamin K Antagonists (VKAs)

There are two types of VKAs:

Coumarin derivatives:
- Acenocoumarol (marketed under the brand 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, accounting for nearly 70% of patients taking vitamin K antagonists. Globally, warfarin is the most commonly prescribed vitamin K antagonist. It should be noted that warfarin is the most extensively studied 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 receiving long-term treatment with fluindione (more than 6 months) who are well-controlled and tolerate the medication well, there is no reason to change the treatment.

Key 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, or herbal product, or before undergoing 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 counteract the anticoagulant effect of vitamin K antagonists (VKAs).
Half-life: Acenocoumarol: 8 hours; Fluindione: 31 hours; Warfarin: 35 to 45 hours. The effect of vitamin K antagonists (VKAs) is less sensitive to missed doses than that of direct oral anticoagulants (DOACs) due to their longer half-life.
Risk of bleeding: VKAs, like DOACs, carry a risk of potentially serious bleeding.
Precautions: Intramuscular injections are contraindicated in patients taking vitamin K antagonists (VKAs). Be careful to avoid falls and injuries that could cause bleeding. It is recommended to use a soft-bristled toothbrush and an electric razor.

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

The use of vitamin K antagonists (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) may be used.

Monitoring of Vitamin K Antagonist (VKA) Therapy: INR

A key and distinctive feature of VKA therapy, compared to DOACs, is the need for regular clinical 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 based on the INR value, with the goal of achieving a "target INR" set by the doctor.

Monitoring the degree of anticoagulation by measuring the INR has a major advantage: the ability to precisely track the effectiveness of treatment and adjust the dose. However, it also has a disadvantage: the need for routine and regular 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 coagulation 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 different 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 consequence 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 is outside the acceptable range (too low or too high).
If you experience any bleeding, even minor, such as bleeding gums, nosebleeds, bleeding eyes (red eye), blood in the urine, abnormally heavy periods, unexplained bruises, black or bright red stools, vomiting or coughing up blood, or a cut or wound that won’t 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 symptoms 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 reduce the anticoagulant effect and increase the risk of thrombosis. For this reason, it is essential NEVER to take any medication, regardless of what it is, without consulting your doctor.

Some substances are contraindicated when taken 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 preferred pain reliever for patients taking 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 (such as fish oils).
Garlic.
Turmeric.
Ginger.
Ginkgo.
Ginseng.
Eleutherococcus.
Kava.
Tonka bean.
White willow.
Other herbal products.

Self-medication is therefore strictly prohibited when taking vitamin K antagonists (VKAs). As a safety precaution, when a doctor prescribes a new medication, they often measure the INR three or four days after starting treatment to ensure 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 Therapy

Living with VKA treatment requires knowing how to handle a variety of 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 highly 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 decision is made to switch, the 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 supply 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 to a destination with a significant time difference, ask your doctor for advice on adjusting your dosing schedule. As mentioned previously, be aware that INR values may vary between laboratories, especially abroad, and consult your doctor. Beware of Accidents and Falls: People taking oral anticoagulants (VKAs) should take care 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 at greater risk of falls, should take steps to make their homes safer. Any fall, especially to 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 therapy 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. Physicians consider several factors when making this decision:

The patient's individual risk of bleeding.
The patient's age and weight.
The patient's kidney function.
The patient's expected level of adherence to treatment.
The patient's ability to monitor the level of anticoagulation by measuring the INR (for vitamin K antagonists).
The patient's preference, after receiving appropriate information about the various 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 with Vitamin K Antagonist Therapy: Adherence and Safety

Once vitamin K antagonist therapy is started, daily self-management by the patient is essential to ensure its effectiveness and safety. Adherence to treatment is vital and must be regularly emphasized to the patient. A regular dosing schedule is recommended.

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

Carrying a card indicating anticoagulant therapy at all times. This document is mandatory. It must specify that the patient should not stop or change the treatment and should not 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) provided 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 scheduled appointments, and the results of laboratory tests performed, particularly the INR. The use of this document, which must be presented to any healthcare professional consulted, aims to ensure better coordination among healthcare providers (doctor, pharmacist, laboratory technician, 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 skipped doses must be recorded.

Communication with Healthcare Professionals: It is essential that patients inform all healthcare professionals they consult that they are taking vitamin K antagonists (VKAs). This includes doctors, pharmacists, laboratory staff, nurses, dentists, physical therapists, podiatrists, etc. This information is crucial because some procedures are contraindicated or require special precautions. For example, intramuscular injections are contraindicated in people taking VKAs. Before any injection, tooth extraction, foot care, minor surgery, or travel plans, it is essential to consult the treating physician. In the event of bleeding, it is imperative to contact your doctor immediately or go to the nearest emergency room.

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.