Back Page | Pradaxa: First Five Months of a New Era

My phone vibrated with an urgent message that read: "Please call. The INR [international normalization ratio] of your atrial fibrillation [AF] patient scheduled for cardioversion is too low. He is on the new blood thinner Pradaxa. What should we do?"

I responded, sounding like an expert "It's OK. Pradaxa thins the blood adequately; it just doesn't change the INR."

She astutely responded, "How do you know the blood is thin? What if the patient doesn't take the medicine faithfully?"

In the treatment of AF, this exchange illustrates a sea change in thinking.

Until five months ago, the only stroke prevention medication for AF was warfarin. Doctors don't like warfarin because of its variable effects, risk of under- or overtreatment and multiple drug/dietary interactions. In the best case, in closely supervised clinical trials, warfarin-treated patients are in therapeutic range only two-thirds of the time. Patients dislike warfarin because of the hassle of frequent INR measurements, and fear of a drug that can cause excess bleeding.

It's hard to put into words the anticipation (and surprise) that dabigatran (Pradaxa, Boehringer Ingelheim) brings. Here are a few upsides of dabigatran:

• Replaces warfarin, whose downsides are legion.
• The science supporting dabigatran is stellar. The 18,000 patient-strong RE-LY trial clearly showed that—for AF patients—dabigatran is a better blood thinner than warfarin. Dabigatran-treated patients had fewer strokes and less intracranial bleeding than those on warfarin.
• INR testing is not needed with dabigatran due to the way it thins the blood.
• No known significant drug or dietary interactions.
• The rapid onset of dabigatran's blood-thinning effect allows for shorter hospital stays. Previously, patients stayed hospitalized on IV (or subcutaneous) blood thinners for the three to five days it took warfarin to adequately thin the blood. Dabigatran shortens this to hours.

While there's a lot to like, dabigatran also has some downsides, including:

• For patients, it will cost much more than warfarin. How much patients are willing to pay for the convenience and superiority of dabigatran remains to be seen.
• It's a twice-a-day drug, which leads to concerns about compliance.
• One in 10 patients who take dabigatran gets heartburn.
• Dabigatran is cleared by the kidneys. Patients who have (or develop) kidney disease require dosing adjustments.
• The vial-dispensed drug expires after 30 days, but is available in blister packs.
• The un-measurability of dabigatran makes doctors nervous. We are still getting used to the foreign notion of not knowing whether the blood is thin, which is important. Consider the above vignette: To protect patients from a dislodged clot, the current protocol before cardioversion mandates three weeks of adequate blood thinning with warfarin, which is confirmed with serial INRs. With dabigatran, no such measurement exists.

I am a cautious early-adopter. I started prescribing dabigatran slowly. It's not just another new medicine; it's a paradigm shift. My approach to dabigatran is to discuss with my patients its risks, benefits, alternatives and expectations, including the drug's newness.

I also emphasize the fact that dabigatran may be especially helpful to AF patients with multiple risk factors for stroke (diabetes, heart failure, previous stroke, high blood pressure or age greater than 75) or those with difficult to control INR levels.

Discussing all of AF treatment in a single office visit is a challenge. Dabigatran makes this task harder. The novelty of how it works, the newness of the concept of a non-warfarin blood thinner and the difficulty of discussing clinical trials has added even more complexity.

In the first five months, I have not seen a major bleed with dabigatran. I also have performed atrial flutter ablations and electrical cardioversions on dabigatran without incident. A couple patients stopped the drug because of heartburn. Many more declined because of cost. In summary, my very early real-world experience with dabigatran looks encouraging.  

Dr. Mandrola is a cardiac electrophysiologist in private practice with Louisville Cardiology in Louisville, Ky. He can be reached at John.Mandrola@gmail.com.