Pradaxa, generic name dibigatron, has the potential to change the way we manage atrial fibrillation to prevent stroke. Stroke is one of the most feared medical problems for many patients, and atrial fibrillation is one of the biggest risk factors for stroke. Stroke is the third leading cause of death in the U.S. and the leading cause of long term disability. Having atrial fibrillation increases a person’s risk of having a stroke about five fold and is the cause of 15-20% of strokes in America, over 100,000 strokes a year. Most patients with atrial fibrillation are candidates for long-term anticoagulation, and until Pradaxa was approved by the FDA in October, 2010 patients were either treated with oral warfarin, injectable low molecular weight heparin, or with less effective anti-platelet medications like aspirin.
Warfarin has been the choice of most physicians and patients for prevention of stroke in patients with atrial fibrillation because it works well. The annual risk of stroke in patients with atrial fibrillation is 4.5% without warfarin anticoagulation, and 1.4% with warfarin treatment. This risk varies a great deal from individual to individual depending on associated risk factors like coexisting hypertension, diabetes, congestive heart failure, prior TIA or stroke and age over 75. A scoring algorithm called the CHADS2 score is often used to better assess an individual’s risk. For most patients the absolute reduction in risk of stroke is high enough that most physicians have encouraged most of their atrial fibrillation patients to take warfarin. Warfarin therapy is no small undertaking though and has very significant bleeding risks. Several major problems are involved with use of warfarin as an anticoagulant:
- A patient has to wait several days for the anticoagulation effects of warfarin to take effect. During this time the patient needs to be tested frequently, sometimes daily, to assess whether the prescribed dose of warfarin is just right.
- It often takes one to several weeks to get the dose just right. Then after the INR is just right they will still need monthly blood tests to assure they remain adequately but not overly anticoagulated. If this sounds like a big hassle and expense you are very perceptive. It is.
- Many drugs interfere with warfarin metabolism and so drug interactions are notoriously difficult to manage in patients on warfarin.
- Because Warfarin is a vitamin K antagonist dietary variation in vitamin K content can have a significant effect on the anticoagulation effect of warfarin.
- The therapeutic window for warfarin dosage is quite narrow, meaning the difference in dose between not enough and too much can be quite small. It is very difficult to predict what dose an individual patient will need.
Pradaxa is approved by the FDA for treatment of atrial fibrillation at a single fixed dose for most patients. It is dosed at 150 mg twice daily, and is effective within hours of taking the first dose. It works at least as well as warfarin to prevent stroke in patients with non-valvular atrial fibrillation, and overall the Pradaxa side effects profile is generally lower than with warfarin. In addition Pradaxa has far fewer drug interactions than warfarin which is notoriously affected by both diet changes and innumerable other medications. Bleeding risks with Pradaxa seem to be about the same overall as with warfarin. There may be a minimally lower risk of major cerebral hemorrhage and a higher risk of gastrointestinal bleeding with Pradaxa vs. warfarin.
The big issue holding back the widespread use of Pradaxa seems to be its cost. In a recent cost effectiveness analysis in the Annals of Internal Medicine for use in patients age >65 with non-valvular heart disease, assuming a daily cost of Pradaxa at $13.60 the conclusion was that Pradaxa has incrememtally higher costs and incrementally higher added years of life. Currently Pradaxa costs $230./ 60 doses , ie. 30 days supply or $7.66/day at Costco.com. With this lower cost than assumed in the study it seems like Pradaxa may win in the cost effective analysis.
I believe this study takes into consideration the lower risk of cerebral hemorrhage complications that can often lead to very expensive hospitalizations and long term nursing home care with Pradaxa. When I talk with other physicians they generally tell me that they would rather deal with GI bleeding, which is slightly more common with Pradaxa, than with intracranial bleeding which is slightly more common with warfarin. I’ll be interested to see more post marketing cost analysis comparisons as they become available, and to see how many patients are switched from warfarin to Pradaxa, and how many new patients are started on each of these medications.
I will not be surprised if as more physicians gain experience with Pradaxa, and more cost analysis is done, that Pradaxa will become the standard of care for treatment of atrial fibrillation for stroke prevention in patients at high enough risk of stroke to warrant the risks of therapy.
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