Gold standard case presentation

NOACs and vitamin K antagonists

Since the advent of the novel oral anticoagulants (NOACs) depending upon what your local policy is the NOACs have become the primary treatment choice for non-valvular atrial fibrillation (NVAF) and thromboembolic disease (pulmonary emobolism and/or deep vein thromboses).  there is still a role for vitamin K antagonists (warfarin) in valvular AF as well as those who are intolerant or allergic to NOACs. If you would like more information with regards to the trials comparing NOACs to vitamin K antagonists here is a screencast lecture that you can watch. Otherwise here is a summary of the different options comparing NOACs and vitamin K antagonists. There has been a lot of debate and discussion with regards to the definitions of valvular and nonvalvular AF the European Society of Cardiology definition of non-valvular AF which is currently used as a counterpoint to non-valvular AF and non-valvular AF ‘is restricted to cases in which the rhythm disturbance occurs in the absence of rheumatic mitral valve disease,  a prosthetic heart valve or mitral valve repair. Vitamin K antagonists are primarily warfarin however in Germany for example they use phenprocoumon – hence from now on we will talk about vitamin K antagonists (VKA). There are currently four NOACs on the market, dabigatran, rivaroxaban, edoxaban and apixaban. All the data that has been carried out with NOACs compares each of them separately with VKA. There are no head-to-head studies and there will likely never be head-to-head-studies and the trials are not easily comparable to help determine which is the best NOAC for which condition. The side effects  of the NOACs are primarily indigestion and nausea, diarrhoea and loose stools and minor bleeding and/or bruising. Major bleeding does occur but on the whole with a reduced incidence compared to VKA. Apixaban has an advantage in reducing the rate of ischemic and hemorrhagic strokes compared to VKA. Dabigatran reduces the number of hemorrhagic strokes compared to VKA and the same for rivaroxaban. When comparing bleeding outcomes, there is a reduction in major bleeds with dabigatran and apixaban and rivaroxaban.

Key features in counselling for vitamin K antagonists

• compliance ensuring VKA tablet is taken at the same time everyday and to not double up doses
• ensure patients know where they can obtain a supply and holiday planning
• explain what the international normalisation ratio (INR) is and the process of regular monitoring and explain the side effects as explained above
  • bleeding Symptoms
    • severe bruising, tea-coloured urine, dark, tarry stools,
    • coughing up blood (coffee-stained), severe headache, prolonged bleeding.
  • Recurrence of thromboembolism
    • new pain, shortness of breath, pain,
    • swelling redness in an extremity, sudden inability to speak, slurred speech,
    • sustained numbness or weakness in arm/leg
• actions to take if bleeding or bruising occur
  • how to manage if patient is vomiting or has diarrhoea
• loading versus maintenance dosing and changing doses compared to INR
• drug and food interactions
  • over-the-counter medicines:
    • Aspirin
    • Ibuprofen
  • ‘health’ Shop herbal remedies
    • Ask pharmacist/GP for advice
  • prescribed Medicines:
    • importance of notifying changes
    • starting/stopping interacting medicines
  • foods high in Vitamin K
    • importance of moderation with Vitamin K rich foods (green vegetable)
    • diet should be well balanced
• moderation of alcohol intake – no more than two units a day
• contraception and pregnancy if appropriate
• surgical procedures including dental work
• avoid intramuscular injections
• avoid sports and activities which may result in serious fall or injury

Medications that interact with VKA:

Gastrointestinal

• Cimetidine
• omeprazole and possibly other PPIs

Cardiovascular

• amiodarone* (liver enzyme inhibition is slow and may persist long after withdrawal requiring weekly monitoring over 4 weeks),
• fibrates
• ezetimibe
• propafenone
• propranolol
• statins – no clinically relevant interaction will normally be seen however it is prudent to check INR in the weeks after initiation and at any dose change

CNS

• Fluvoxamine
• SNRIs
• SSRIs
• tramadol

Antibiotics

• co-trimoxazol
• macrolides (can be serious but unpredictable)
• metronidazole
• quinolones (can be serious but unpredictable)
• tetracyclines
• influenza vaccine

Endocrine

• anabolic steroids (and danazol)
• high dose corticosteroids,
• glucagon (high dose 50mg+ over 2 days)
• Flutamide
• levothyroxine

NSAIDs

• ibuprofen at lowest effective dose (+/-PPI) is probably safest if NSAID is required
• N.B. All NSAIDs can increase the risk of bleeds and should be avoided if possible

Antiplatelets – increased bleed risk Aspirin, clopidogrel and dipyridamole

Miscellaneous

• alcohol (acute)
• allopurinol
• benzbromarone
• colchicine
• disulfiram
• Fluorouracil,
• interferon
• paracetamol (prolonged use at high dose)
• sulfinpyrazone
• tamoxifen
• topical salicylates
• zafirlucast
• Anti-infectives (antiinfectives in general may cause raised INR’s) azole antifungals* (esp. miconazole including oral gel and vaginal)

Herbal preparations/Food supplements

• carnitine, chamomile, cranberry juice, curbicin, dong quai, fenugreek, fish oils, garlic, gingo biloba, glucosamine, grapefruit juice, lycium, mango, quilinggao

Drugs that decrease the INR

Miscellaneous

• alcohol (chronic)
• azathioprine
• barbiturates
• bosentan
• carbamazepine
• carbimazole
• griseofulvin
• mercaptopurine
• nevirapine
• OCP/HRT
• propylthiouracil
• raloxifene
• rifampicin (most potent inducer)
• trazodone

Herbal preparations

• avocado
• co-enzyme Q10
• green tea
• natto
• soya beans
• St Johns wort (avoid)

Binding agents

• colestyramine
• sucralfate

NICE criteria for commencing a NOAC for stroke prevention and non-valvular AF:

Dabigatran is an option if: Non-valvular AF and NICE TA 249 criteria are satisfied, i.e. one or more of the following risk Factors:

• Previous stroke, TIA or systemic embolism

• Left ventricular ejection fraction below 40%

• Symptomatic heart failure of New York Heart Association class 2 or above

• Age 75 years or older
• Age 65 years or older with one of the following: diabetes mellitus, coronary artery disease or hypertension

Rivaroxaban is an option if: Non valvular AF and NICE TA 256 criteria are satisfied, i.e. one or more risk factors such as:

• Congestive heart failure
• Hypertension
• Age 75 years or older
• Diabetes mellitus
• Prior stroke or TIA

Apixaban is an option if: Non valvular AF and NICE TA 275 criteria are satisfied, i.e. one or more risk factors such as:

• Prior stroke or TIA
• Age 75 years or older
• Hypertension
• Diabetes mellitus
• Symptomatic heart failure

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