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Drug reviews: use, side effects, effectiveness,  drug vs drug

Apixaban vs warfarin: rise of newer anticoagulant

Apixaban (Eliquis®) and warfarin are two popular prescription-only drugs classified as anticoagulants, commonly known as blood thinners. Warfarin has been used as an anticoagulant for a very long time. However, in recent years warfarin’s popularity decreased in place of newer anticoagulants such as apixaban, as reflected by prescribing statistics. Apixaban vs warfarin, a summary of the post:

  • Apixaban vs warfarin: Are they used to treat the same conditions?
  • Differences in mechanism of action between
  • Do apixaban and warfarin need drug monitoring?
  • Other advantages of apixaban vs warfarin
  • Prescribing statistics
  • Apixaban vs warfarin common side effects
  • Is apixaban better than warfarin?

Apixaban and warfarin are classified as blood-thinning drugs. Warfarin has a long history of use going back to 1950′ when it was approved for human use, and until recent years its been the most popular anticoagulant used in the UK. The popularity of warfarin has been driven mainly by two factors, effectiveness and low cost of the drug.

Apixaban, on the other hand, is a newer generation anticoagulant. Together with dabigatran (Pradaxa®), edoxaban (Lixiana®) and rivaroxaban (Xarelto®), apixaban belongs to a grop of drugs called the novel oral anticoagulants (NOACs).  

In the UK, apixaban is known as a branded drug called Eliquis®. In 2019, the first generic version of Eliquis® was approved in the US. Eliquis is still protected by patent rights in the UK, with exclusive availability rights until 2026 (IPO, 2021). 

Eliquis tablets: Apixaban 5mg tablets

Apixaban vs warfarin: differences in licensed use

Warfarin is licensed for treatment/prevention of the following conditions:

  • Prevention of clot formation in patients with rheumatic heart disease and atrial fibrillation (AF)
  • Prevention of clot formation in patients who had prosthetic heart valves inserted
  • Prevention and treatment of venous thrombosis (for example, deep vein thrombosis/DVT) and pulmonary embolism (a blood clot in the lungs).
  • Prevention of mini-strokes

Apixaban, on the other hands, is licensed for:

  • Prevention of strokes and blood clots formation in patients with non-valvular atrial fibrillation (NVAF) who additionally have another risk factor (one or more), for example, previous stroke or a ‘mini’ stroke, age 75 or over, high blood pressure (hypertension), diabetes, heart failure (class II or above)
  • Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE – blockage of blood vessels in the lungs), and prevention of recurrent DVT and PE in adults

Although not precisely the same, warfarin and apixaban have similar licensed use. Both drugs are used as anticoagulants to treat or prevent the formation of blood clots in the body.

The formation of a blood clot can lead to health emergencies such as stroke or heart attack.

Does apixaban have the same mechanism of action as warfarin? 

Warfarin and apixaban have a different mechanism of action. Warfarin stops the production of Vitamin K, which plays a role in blood clotting in the body, including wound healing and the formation of blood blots.

Apixaban is sometimes (incorrectly) called a non-Vitamin K antagonist. As the name suggests, apixaban and other newer anticoagulants do not affect vitamin K production.

Apixaban stops the production of enzymes (chemicals) required for the production of fibrin, a compound (protein) that plays a role in the clotting of the blood.

Although the end effect is very similar for both drugs, their mechanism of action is entirely different, which offers some treatment advantages with novel anticoagulant drugs.

Drug monitoring requirements for apixaban and warfarin

Perhaps one of the main disadvantages of warfarin therapy is the need for regular blood check (coagulation checks) to determine the International Normalised Ratio (INR). INR indicates how long it takes for the blood to clot. Higher INR means it takes longer for the blood to clot.

Patients have an INR target set between 2-3 (2.5 is a usual target). However, the INR target may differ, depending on the conditions treated. It is common for INR to change. When INR changes, patients need to adjust their dose by increasing or decreasing the number of warfarin tablets they take.

Does apixaban need regular blood checks?

Apixaban does not require regular blood checks to determine blood coagulation. Additionally, the dosage is much simpler as compared to warfarin as it does not change generally after treatment initiation is completed. 

Apixaban is usually taken twice a day. The actual dose depends on the condition treated. For example, the initial apixaban dose (first seven days) for DVT treatment or PE is higher. After seven days, a standard dose of 5mg twice a day is taken. Follow the directions from your prescriber on how to take apixaban.

As with many other drugs, patients may need to have a follow-up visit with GP to review the treatment and discuss any side effects. A blood test to assess renal (kidney) function may be required during the treatment with apixaban and other

Pharmacies in the UK can also be offered a free NHS service called New Medication Service (NMS). As part of this service, patients are contacted by a pharmacist a week and three weeks after a new medication is started.

Advantages of apixaban treatment

Advantages of the treatment with apixaban can easily be identified by contrasting the treatment to warfarin:

  • Starts to work faster
  • No need for drug monitoring
  • Not classified as a narrow therapeutic drug like warfarin (variation in drug concentration are not observed as with warfarin treatment)
  • Fewer interactions with other drugs, including over the counter medicines
  • No dietary restrictions

Apixaban vs warfarin: common side effects

British National Formulary (BNF) list the following common side effects for apixaban and warfarin:

  • Apixaban
    • Anaemia
    • Nausea
    • Haemorrhage, for example, Gastrointestinal haemorrhage
    • Skin reactions
    • Warfarin
    • Haemorrhage

 Product information leaflets for both drugs list more possible side effects. Product information leaflets can be found at medicines.org.uk.

Is apixaban is more effective than warfarin?

One of the primary studies which compared the effectiveness of warfarin and apixaban was the ARISTOTLE study. 18,201 patients took part in this study. All patients had atrial fibrillation (the irregular rhythm of the heart), with another risk factor for a stroke. The effectiveness of apixaban and warfarin was investigated in the prevention of ischemic (blood vessel in the brain blocked by a clot) and haemorrhagic strokes (rupture of blood vessel in the brain and consequent leak of blood in the brain). This trial also looked at rates of major bleeds and deaths from any reasons during the trial. Main results from the trial (Granger et al., 2011):

  • Apixaban was superior (better) to warfarin in preventing stroke/ clots formation in patients with atrial fibrillation.
  • Apixaban was associated with less bleeding than warfarin.

Which drug is more popular, apixaban or warfarin?

Apixaban vs warfarin: prescribing statistics in England
Graph: Druggist.Online Data source: OpenPrescribing.net

It is clear from the graph below that apixaban became a more commonly prescribed anticoagulant in England. Warfarin prescribing has been on the decrease in place of apixaban and other warfarin alternative drugs.

Can I be switched from apixaban to warfarin?

It is now evident that novel anticoagulant drugs became a more favourable treatment choice than warfarin. Patients who currently take warfarin may be offered to switch to newer anticoagulants. Not all patients who require anticoagulant therapy may be offered to switch from warfarin to a newer anticoagulant drug. Examples of patients who should not be changed from warfarin to apixaban or other newer anticoagulant (Williams, 2020):

  • Patients with prosthetic mechanical valve
  • Pregnant or breastfeeding women
  • Patients who have an IRN target outside the standard range (2.0-3.0)
  • Patients with severe renal (kidney) impairment
  • Patients who have cancer or receive chemotherapy
  • Patients who take drugs, which interact with novel anticoagulant drugs, for example, HIV individuals some n antiretrovirals and hepatitis antivirals.

More details can be found in a document called Guidance for the safe switching of warfarin to direct oral anticoagulants (DOACs) for patients with non-valvular AF and venous thromboembolism (DVT / PE).

Each DOAC has specific information on switching from warfarin. Generally, a newer anticoagulant is initiated after stopping warfarin, and the patient reached the appropriate INR. For example, for apixaban, patients INR need to drop below 2. During switching time, patients may be asked to do an INR test (blood test) daily.

 

References:

1. Apixaban Monograph for Professionals – Drugs.com Accessed on 30/04/2021.
2. Warfarin Anticoagulant Medication (clevelandclinic.org) Accessed on 30/04/2021.

I am a community pharmacist working in UK. I blog about drugs, health and pharmacy.

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