Published in the April 2011 issue of Today’s Hospitalist
WHEN THE ANTICOAGULANT DABIGATRAN was approved by the FDA late last year, some analysts predicted that the therapy would usher in a paradigm shift.
Clinical trials have shown that compared to warfarin, dabigatran reduced the incidence of thromboembolic strokes by 30% and intracerebral bleeding by 60% among patients with nonvalvular atrial fibrillation. In addition, dabigatran is an oral agent that doesn’t require patients to undergo regular INR checks.
But dabigatran is still a new drug, at least in the U.S., and physicians have some concerns. Because the drug has a short half-life (it must be taken twice a day), patients who miss too many doses may wind up with inadequate anticoagulation. While the drug has a solid safety profile, data point to an elevated risk of GI bleeding among older patients. And because the therapy must be cleared through the kidneys, it presents challenges for patients with renal problems.
To assess the impact that dabigatran will have on physicians in general “and hospitalists in particular “we talked to cardiologist Samuel Z. Goldhaber, MD, a nationally known expert on anticoagulation who has been moderating a discussion about the drug at the New England Journal of Medicine’s CardioExchange blog (www.cardioexchange.org). Dr. Goldhaber is professor of medicine at Harvard Medical School, staff cardiologist at Boston’s Brigham and Women’s Hospital and medical co-director of Brigham and Women’s anticoagulation management service.
Dabigatran is relatively new. Is it important for hospitalists to know this drug?
If a patient comes into the hospital on dabigatran, hospitalists need to be familiar with it, just like any other medication. And for new onset atrial fibrillation, when the decision is made that a patient is at sufficiently high risk to warrant anticoagulation to prevent stroke, dabigatran is going to be the first choice for most patients because it has a 30% lower stroke rate than warfarin.
Those data come from the RE-LY study, published in the New England Journal of Medicine in 2009. This is the only trial where warfarin, which was first marketed in 1954, has been beaten.
What do data say about the safety of dabigatran?
In terms of the safety profile, the big difference is the 60% lower rate of head bleeding. In elderly patients, there was more GI bleeding with dabigatran than warfarin, but the overall safety profile looked excellent.
Who are the early adopters of the drug?
Among cardiologists, electrophysiologists are really embracing dabigatran. These are the people doing the ablations and using various drug therapies to suppress atrial fibrillation, so they have received the drug with open arms.
To which of your patients are you giving dabigatran?
For new onset cases of atrial fibrillation that meet the risk score of CHADS2 or higher, where anticoagulation is unequivocally recommended, dabigatran would be my default choice “barring end-stage renal disease in patients with a creatinine clearance of less than 15.
For patients taking warfarin who are doing fine and are within the therapeutic range, there’s no particular reason to rock the boat. But dabigatran will be particularly useful for patients who are already taking warfarin and are having trouble staying within therapeutic range.
How can physicians know if dabigatran is working for their patients? There’s no lab value (like an INR with warfarin) to reference.
Prescribing this drug is really a matter of faith, based on trial data. It requires a new mindset, just like low molecular weight heparin when it was introduced in the early 1990s. Then, as now, there was concern that we had no routine way to monitor coagulation. We were prescribing fixed doses of low molecular weight heparin on the basis of weight. Now, we’re dosing dabigatran as a fixed dose.
Dabigatran costs significantly more than warfarin. How do you justify the additional costs?
Dabigatran wholesales for about $6.75, and most of the time you can get a 5 mg warfarin pill for 75 cents wholesale, so there’s a difference in price. But if you include the cost of treating excessive strokes and head bleeds with warfarin, warfarin is much more expensive. And if you take into account not just the cost of the medication but the cost of a nurse or pharmacist to regulate warfarin, the cost of an anticoagulation management service and the cost of regular INRs, dabigatran looks more cost effective.
How are payers handling prescriptions?
I haven’t heard that payers are rejecting prescriptions. Most are sending prescriptions back to physicians for preauthorization, and some are asking for physicians to supply additional information.
There’s no antidote for dabigatran. Is that a problem?
It could be. The effects typically wear off in about 12 hours. In catastrophic circumstances, the drug can be removed by hemodialysis.
What concerns should physicians prescribing dabigatran keep in mind?
It’s important to emphasize to patients that they have to comply with twice-daily dosing. This is not warfarin, and you can’t forget one or two doses and still have some anticoagulation effect. Dabigatran should not be prescribed to patients who have problems with medication adherence, so for patients not taking their warfarin daily, this would not be a good choice.
The drug should also be taken with food. I’m finding that a lot of patients don’t really have much for breakfast except for coffee, so they need to change their breakfast habits with dabigatran.
The drug should not be used in patients in end-stage renal failure, and there’s a 2% discontinuation rate because of dyspepsia. And when switching from warfarin, you may have to omit one or two doses of warfarin and switch when the INR falls below 2.0.
What do hospitalists need to know about stopping and starting the drug around surgeries?
If patients have normal renal function, omit one or both doses of dabigatran the day before surgery. If the patient cannot tolerate any perioperative anticoagulation at all, then omit both doses the day before.
Don’t use dabigatran on the day of surgery and confer with the surgeon to determine how soon it is safe to resume anticoagulation postoperatively. Remember, the patient will be fully anticoagulated within two hours of taking dabigatran.
Edward Doyle is Editor of Today’s Hospitalist.