Atrial Fibrillation – A common indication for warfarin therapy plus monitoring

Coagulation Information: Indications for PT/INR Monitoring / Atrial Fibrillation

Atrial Fibrillation

Atrial fibrillation is the most common heart rhythm abnormality that people develop. During AF the heart's two upper chambers (the atria) beat chaotically and irregularly. The condition causes poor blood flow and the development of blood clots within the heart which can subsequently release into the arteries of the brain and cause a stroke. It is primarily a problem of the elderly.




AF is often classified as follows:

  • Recurrent AF: two or more episodes of AF
  • Paroxysmal AF: episodes end spontaneously within seven days
  • Persistent AF: pharmacologic or electrical cardio-version is required to terminate the arrhythmia
  • Permanent AF: sustained AF despite treatment to end the arrhythmia or when cardio version is inappropriate

Approximately 15% of strokes occur in patients with atrial fibrillation (AF). The risk of stroke in AF patients increases with age, from a 1.5% annual risk in patients aged 50-59 years to 23.5% in those aged 80-89 years. Indeed, elderly patients with AF are at the highest risk for stroke and the highest risk for hemorrhage. After adjusting for comorbid cardiovascular conditions, AF is associated with a 50% to 90% increase in mortality risk. Furthermore, stroke is a leading cause of serious long-term disability.

It has been recently estimated that around 5.6 million US and around 4.5 million EU citizens suffer from paroxysmal or persistent atrial fibrillation today. This number may increase in the US alone up to 15 Million people.  During the last 20 years there has been a 66% increase in hospitalizations due to atrial fibrillation and atrial fibrillation is regarded as one of the major risk factors for thromboembolic-caused stroke.

Anticoagulation

Five landmark clinical trials - AFASAK, SPAF, BAATAF, CAFA, and SPINAF - have demonstrated the unequivocal benefits of warfarin in preventing stroke among patients with AF. Below 2.0, patients have an increased risk for ischemic stroke, and above 3.0, the risk for intracranial bleeding begins to rise.

According to a large European fibrillation study from Hart et al., involving more than 1,000 patients, a risk reduction for stroke from 12% to 4% was achieved for this clinical picture. In other words, the number of stroke events can be reduced by 80 in every 1,000 patients treated with anticoagulants.
This was confirmed recently by the BAFTA study showing that stroke risk is lowered by 64 % and death by 25 % with VKA compared to no treatment, and stroke is reduced by 22 % with antiplatelet agents.
Warfarin is 40 % more efficacious than antiplatelet therapy and is appropriate in elderly population

Where oral anticoagulation is indicated, a risk stratification (e.g. using the CHADS2 score) must be performed. The CHADS2 scoring system assigns 1 point to each of four risk factors for stroke: Congestive Heart Failure, Hypertension, Age ≥75 years, and Diabetes. In addition, 2 points are assigned for prior Stroke, TIA, or systemic embolus. The annual risk for stroke is directly related to CHADS2 score, ranging from 1.9% for a CHADS2 score of 0 to 18.2% for a CHADS2 score of 6.

Guidelines:
The latest ACC/AHA/ESC AF guidelines confirm the need and benefits of oral anticoagulation in most patients. For patients with a CHADS2 score >1, the guidelines recommend warfarin therapy (INR 2.0-3.0) for long-term risk management.

Open questions:

  • Limited Compliance
    Despite considerable evidence supporting the use of anticoagulation therapy in the management of AF, warfarin is under-utilized across treatment settings. In a survey of community and academic hospitals in the US, nearly half of high-risk AF patients (47%) were not being treated with warfarin therapy.  In a European survey, only 54% of high-risk AF patients were receiving warfarin therapy.
    Long-term adherence to warfarin therapy is also low among patients with AF. Up to 25% of patients aged 80 years or older discontinued therapy within 90 days for reasons excluding death or return to normal sinus rhythm.  Factors associated with decreased use of oral anticoagulation include perceived bleeding risk, lack of proximity to an INR monitoring site, patient preference, and the innate difficulties of warfarin use.
  • Elderly patients
    The recent prospective randomised BAFTA trial assessed whether warfarin reduced the risk of major stroke or embolism without impacts on major haemorrhages as compared to acetylsalicylic acid in elderly patients.
    Findings indicated the benefit of warfarin over acetylsalicylic acid for stroke prevention (70% reduction in risks with warfarin use vs. acetylsalicylic acid) with significantly lower complication rates and similar risks of major haemorrhage (1.9% vs. 2.0% haemorrhage risk per year). Therefore, anticoagulation therapy is recommended for people with AF over 75 years old, unless there are contraindications.
    The safety and efficacy of oral anticoagulation self-management in elderly patients was confirmed by a randomized controlled trial from Siebenhofer et al. in 2007.
  • New anticoagulants
    New anticoagulants which do not require continuous monitoring are currently under evaluation for stroke prevention in AF.
    Presently, there are nevertheless no alternatives better than vitamin K antagonists for stroke prevention in atrial fibrillation (SPAF)