Action plan for warfarin anticoagulation in atrial fibrillation By Oluwole A. Williams, B.Sc., Pharm.D., R.PH.

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Atrial fibrillation (Afib) is a disorder of heart rhythm, also known as an arrhythmia. It is now an increasingly common disease, particularly in elderly persons of over 60 years of age. There are approximately 160,000 new incidences of Afib annually in the United States alone, each patient requiring proper care and management to prevent the occurrence of a stroke due to circulating blood clots.
People with Afib may be on medication treatments to stabilise/normalise their heart’s electrical conduction; or they may be surgically treated by the placement of a pacemaker device.
Among those that may suffer an Afib are people suffering from hyperactive thyroid glands, those with diseases of the heart’s mitral valve, and those with genetically induced malformations of the heart’s musculature. These patients will require a well co-ordinated counselling and treatment programme for better understanding of their ailment and for survival.
Some symptoms of an atrial fibrillation are: chest pain, palpitations, syncope and or fainting spells due to an heart failure. The irregular heartbeats and misfiring of electrical impulses seen in Afib may lead to pooling of blood, stasis and clot formation in the upper chamber of the heart. The clots formed may dislodge and travel through the blood vessels into the brain causing an occlusion and stroke.
Prevention of a stroke, management of Afib and treatment compliance, especially for oral anticoagulants is critical to the management of patients living with atrial fibrillation. Warfarin is an important oral anticoagulant that is commonly used in Afib, and its role as an anticoagulant is discussed comprehensively in this action plan. Aspirin, an antiplatelet is also used for its efficacy in preventing clot formation.

What drugs are used in Afib?
Your prescriber may recommended different kinds of medications in the management of your condition, depending on the diagnosis and perceived origin of the atrial fibrillation. Examples of these medications are listed below:
• Anticoagulants: Warfarin, Enoxaparin, Heparin.
• Antiplatelets: Aspirin, Clopidrogel, Cilostazol, and Dabigatran.
• Beta-blockers: Sotalol.
• Antiarrhythmics: Quinidine, Procainamide, Flecainide, Propafenone, Disopyramide, and others, Amiodarone, Dronaderone, Dofetilide ,Ibutilide.
• Calcium channel blockers: Verapamil and Diltiazem.
• Digoxin.

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Warfarin as an oral anticoagulant in atrial fibrillation
The use of warfarin in the management and prevention of complications of Afib is discussed here in detail because it is the most widely used oral anticoagulant agent for the prevention of strokes in Afib patients. Other than the need for monitoring of its effectiveness with an INR or PT Time test, warfarin is efficacious, cheap and tolerable in most patients with Afib.
Warfarin is superior to aspirin or clopidrogel, whether both agents are used singly or combined. It is preferred over dabigatran because it’s hepatically metabolised and can be used in patients with renal failure. The starting doses of warfarin in most cases are: 5MG in the elderly, 7.5MG in obese patients or 2.5MG in patients with very lean body mass.
Warfarin’s effect may take up to seven days to manifest, therefore most patients are first given heparin or low-molecular weight heparins (LMWH) together with oral warfarin if patient can be orally dosed. Most hospitals in the US do have standard warfarin dosing protocols for initiation therapy and for maintenance based on the patient’s Lab values of the INR and comorbid conditions.
Warfarin education and treatment counselling is an essential component of pharmaceutical care for patients who require continuous anticoagulant therapy in atrial fibrillation management. Following admission for an acute episode of Afib, and subsequent patient stabilisation and effective resolution of blood clots (if any) with LMWH or heparin infusion, the patient is initiated on warfarin for a continuous anticoagulation therapy.
Warfarin doses have to be taken daily and continuously for a life time in most Afib patients. The patient, if active, and family members or care-givers are educated appropriately by the clinical pharmacists on duty on the anticipated side-effects, adverse drug reactions, precautions, food-drug interactions and herb-drug interactions of warfarin.

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How warfarin works in preventing complications of Afib
Warfarin works by inhibiting a liver enzyme known as vitamin K epoxide reductase(VKOR) which converts natural vitamin K to the active form for the production of clotting factors (II, VII, IX and X). In this way, warfarin helps reduce the chances of blood clot formation, reducing the risks of a stroke in atrial fibrillation. It also slows the production of certain proteins: Proteins C, S and Z which are called anticoagulant proteins.
Warfarin doses must be taken daily to be effective in the prevention of clots in Afib. If doses are missed or skipped, the effectiveness is compromised. If warfarin doses are doubled, the risks of bleeds from the nose, gums, skin cuts and other body cavities are increased. Warfarin’s effect may be reduced or increased by some other drugs that a physician or dentist prescribes. The effect of warfarin is increased by drugs such as: Aspirin, Clopidrogel, Dabigatran, Cilostazol.
Some pain relief drugs used in arthritis may increase your risks of bleeding with warfarin, examples are: Naproxen, Ibuprofen, Nabumetone, Ketorolac, Diclofenac, Sulindac and Indomethacin. Inform your dentist appropriately that you are a warfarin patient. Use of certain steroids, orally or topically, may also increase your chances of skin bruises and bleeds with warfarin. Drugs or medications that interfere with warfarin metabolism or elimination from the body may equally prolong its effects and adverse reactions. These include: metronidazole, co-trimoxazole such as Batrim or Septra brands and their generic equivalents, as well as some medications used for high lipids- rosuvastatin, atorvastatin and simvastatin.

What’s the duration of warfarin treatment?
Oral doses of warfarin prescribed by a doctor or clinical pharmacist must be taken regularly and consistently as instructed, to prevent unfavourable circumstances and complications of Afib. Clinic visits need to be adhered to, so the doctor’s office may check the effectiveness of warfarin through the INR (International Normalised Ratio) Test, or by the PT (Prothrombin Time) Test.

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Side-effects of warfarin use
These include skin bruises, purple-toes syndrome, gum bleeds, stomach upsets, nausea, taste alterations, chills, numbness, muscle weakness, dizziness etc. Inform your physician or pharmacist immediately if you notice or experience any of the following:
*Bruises, Gum bleeds, or Bright-red colour stools.
*Head injuries from falls
*Unusual dizzy-spells, fainting, light-headedness or extreme weakness.
*Pregnancy, excessive period bleeds or blood in urine.
*Bright-Red or coffee-brown coloured stools.

Monitoring of warfarin effects
The effectiveness of warfarin is measured at clinic visits by the test known as the International Normalised Ratio (INR). The INR is a standardised test used in monitoring whether warfarin levels in the blood are maintained and normal for the prevention of blood clots.
In Afib patients, an INR goal of 2.0–3.0 is the target. INR values of less than 1.8 has been shown to double the risk of a stroke.

General goals of treatment in atrial fibrillation
(a) To reduce rapid heart rate
(b) To effect a control of irregular heartbeat or tachycardia
(c) To use an anticoagulant for stroke prevention
(d) To get the patient into normal heart rhythm.

References
1. Lopes RD, Crowley MJ, Shah BR et al, Stroke Prevention In Atrial Fibrillation(Internet); Agency For Healthcare Research and Quality(US); 2013 Aug. Report No. 13-EHC113-EF
2. Stuart J et al; Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009, 361: 1139 – 1151, September 17, 2009.
3. Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D; Warfarin versus aspirin for Stroke Prevention in an elderly population with atrial fibrillation – The Lancet vol. 370, Issue 9586; 11 – 17, August 2007.

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