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Atrial Fibrillation

Target INR Levels in AF and for Mechanical Prosthetic Heart Valves

In those with atrial fibrillation (AF)

There is now reasonably good evidence that the risk of thromboembolism increases quite markedly when the INR falls below 2.0 . For example, one case-control study showed that compared to an INR of 2.0, an INR of 1.7 doubles the risk of stroke.

A study published in 2003 in the New England Journal of Medicine also reported that patients with atrial fibrillation were much more likely to have a disabling stroke if the INR levels were subtheurapeutic ie below 2.0.

The risk of major haemorrhage seems to be slightly higher with INR levels between 3 and 4, but the risk increases more markedly with INR levels over 4.

As an approximate guide, one could assume that the increased annual risk of major haemorrhage from anticoagulation with warfarin is 0.5% per yr in those under 65 years, and approximately 2% per yr in those older than 75 years. One would expect the risk of intracranial haemorrahge will be less with good control of hypertension.

The annual risk of bleeding may well be lower after a period of anticoagulation therapy. In other words those that are able to continue anticoagulant therapy without complications effectively self-select themselves as being at lower risk of bleeding. In the ACTIVE-W trial, those that were already on anticoagulant therapy at entry into the trial had a significantly lower risk of bleeding.

We should aim for an INR of 2.5-3.0 in most patients. I think aiming for an INR level just over 2.0 carries with it the risk that the INR will fall below 2.0 due to the apparently random fluctuations in responsiveness to warfarin. This fall in INR below 2.0 is associated with increased risk of stroke. On the other hand, aiming for an INR of at least 2.5 is not associated with a significant increase in risk of major bleeding compared to an INR level of just over 2.0.

With reference to mechanical prosthetic valves

We should aim for higher INR in higher risk patients- ie closer to 3.0. Higher risk situations include: presence of a ball&cage type valve (eg Starr-Edwards), or the valve is in the mitral position, or if there are prosthetic valves in both mitral and aortic positions. Those with prosthetic heart valves and with chronic atrial fibrillation, particularly with enlargement of the left atrium, can also be regarded as being at higher risk. Some also advocate routine use of low dose aspirin with warfarin in higher risk patients

Hitesh Patel, Cardiologist
6th August, 2006

References:

  • An analysis of the lowest effective intensity of prophlylactic anticoagulation for patients with nonrheumatic atrial fibrillation, N Eng J Med 1996;335:540-6
  • Effect of Intensity of Oral Anticoagulation on Stroke Severity and Mortality in Atrial Fibrillation. N Engl J Med 2003;349:1019-26
  • Optimal anticoagulant therapy in patients with mechanical heart valves, N Eng J Med 1995;333:11-7
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