Rajat Deo, MD, assistant professor of medicine at the University of Pennsylvania

It is very challenging to maintain an adequate time and therapeutic range, or an adequate INR (international normalized ratio), in our patients who are on warfarin for atrial fibrillation and stroke prevention. It is important to recognize that in the recent phase III clinical trials that have evaluated the efficacy and safety of each one of the 4 NOACs (novel anticoagulants) to warfarin for stroke prevention in the nonvalvular atrial fibrillation patients, the time and therapeutic range in the nonintervention group was on the order of about 65%—meaning, again, 2 out of 3 individuals in the control arm for these studies had an adequate time and therapeutic range. So, that’s quite problematic.
 
That suggests to me that in the most optimal conditions in a large phase III multimillion-dollar clinical trial, at the very best, we can get about a 65% time and therapeutic range. One-third of the time, our patients are not in the adequate therapeutic range with warfarin therapy. I think that suggests that when we look at larger populations, real-world populations (my clinical practice or others), the time and therapeutic range is probably lower.
 
Overall, I believe it is challenging to maintain an effective therapeutic range using warfarin therapy in our atrial fibrillation patients. Our patients confront several physiologic factors and other comorbidities. They take other medications, their diet changes, and these are factors that influence the effectiveness of warfarin therapy and the time and therapeutic range.
 
A reversal agent for any anticoagulant is important. Ideally, an individual who is on an anticoagulant medication and experiences the side effect of bleeding would be under close supervision or monitored care, such that a reversal agent could be administered immediately. We recognize, however, that most bleeding events don’t occur in the hospital or under a supervised condition. And as a result, a catastrophic bleeding complication that results in a life-threatening situation may not benefit from a reversal agent because it may be too late by the time the patient presents to the emergency room. That being stated, a reversal agent, as I indicated, could be useful, especially for a periprocedural bleeding, for intraoperative bleeding, or for conditions when an individual does make it to the emergency room, to prevent a further complication of a bleeding event.
 
Warfarin is a medication that has been used for decades, and we understand its pharmacodynamics (pharmacokinetics) quite well. We also understand, from hundreds of various clinical studies, that warfarin can be an effective therapy when used the right way.
 
So, that point, past prior clinical experience, certainly weighs in in our confidence for using warfarin therapy in various situations, especially for stroke prevention and atrial fibrillation patients. However, warfarin certainly has its disadvantages as well. The biggest disadvantage is that the time and therapeutic range, or the amount of warfarin that is used to maintain an adequate anticoagulation state, can vary on a day-to-day basis as the patient’s physiology or own state-of-health changes. That makes warfarin use extremely challenging because we’re not sure of, at any given point, the individual’s INR and if the warfarin therapy is maximally effective. I believe that, in the end, warfarin is effective, but close monitoring is certainly required.
 

Use of Warfarin in Nonvalvular Atrial Fibrillation

Rajat Deo, MD, remarks on the advantages and disadvantages of warfarin use in preventing stroke in patients with nonvalvular atrial fibrillation.
Published Online: April 18, 2017


Rajat Deo, MD, assistant professor of medicine at the University of Pennsylvania

It is very challenging to maintain an adequate time and therapeutic range, or an adequate INR (international normalized ratio), in our patients who are on warfarin for atrial fibrillation and stroke prevention. It is important to recognize that in the recent phase III clinical trials that have evaluated the efficacy and safety of each one of the 4 NOACs (novel anticoagulants) to warfarin for stroke prevention in the nonvalvular atrial fibrillation patients, the time and therapeutic range in the nonintervention group was on the order of about 65%—meaning, again, 2 out of 3 individuals in the control arm for these studies had an adequate time and therapeutic range. So, that’s quite problematic.
 
That suggests to me that in the most optimal conditions in a large phase III multimillion-dollar clinical trial, at the very best, we can get about a 65% time and therapeutic range. One-third of the time, our patients are not in the adequate therapeutic range with warfarin therapy. I think that suggests that when we look at larger populations, real-world populations (my clinical practice or others), the time and therapeutic range is probably lower.
 
Overall, I believe it is challenging to maintain an effective therapeutic range using warfarin therapy in our atrial fibrillation patients. Our patients confront several physiologic factors and other comorbidities. They take other medications, their diet changes, and these are factors that influence the effectiveness of warfarin therapy and the time and therapeutic range.
 
A reversal agent for any anticoagulant is important. Ideally, an individual who is on an anticoagulant medication and experiences the side effect of bleeding would be under close supervision or monitored care, such that a reversal agent could be administered immediately. We recognize, however, that most bleeding events don’t occur in the hospital or under a supervised condition. And as a result, a catastrophic bleeding complication that results in a life-threatening situation may not benefit from a reversal agent because it may be too late by the time the patient presents to the emergency room. That being stated, a reversal agent, as I indicated, could be useful, especially for a periprocedural bleeding, for intraoperative bleeding, or for conditions when an individual does make it to the emergency room, to prevent a further complication of a bleeding event.
 
Warfarin is a medication that has been used for decades, and we understand its pharmacodynamics (pharmacokinetics) quite well. We also understand, from hundreds of various clinical studies, that warfarin can be an effective therapy when used the right way.
 
So, that point, past prior clinical experience, certainly weighs in in our confidence for using warfarin therapy in various situations, especially for stroke prevention and atrial fibrillation patients. However, warfarin certainly has its disadvantages as well. The biggest disadvantage is that the time and therapeutic range, or the amount of warfarin that is used to maintain an adequate anticoagulation state, can vary on a day-to-day basis as the patient’s physiology or own state-of-health changes. That makes warfarin use extremely challenging because we’re not sure of, at any given point, the individual’s INR and if the warfarin therapy is maximally effective. I believe that, in the end, warfarin is effective, but close monitoring is certainly required.
 
View More From This Discussion
Episode 1 Nonvalvular Atrial Fibrillation and Risk of Stroke
Episode 2 Use of Warfarin in Nonvalvular Atrial Fibrillation
Episode 3 Differentiation of Direct Oral Anticoagulants for Nonvalvular Atrial Fibrillation
Episode 4 Treatment With Direct Oral Anticoagulants for Nonvalvular Atrial Fibrillation
Episode 5 Considerations With Direct Oral Anticoagulants for Nonvalvular Atrial Fibrillation
Episode 6 Reversal Agents for Direct Oral Anticoagulants
Episode 7 Anticoagulant Use to Prevent Stroke in Patients With NVAF
Episode 8 Use of Warfarin in Nonvalvular Atrial Fibrillation
Episode 9 Differentiation of Direct Oral Anticoagulants for NVAF
Episode 10 Drug Monitoring and Reversal Agents for Direct Oral Anticoagulants
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