Bleeding risk from new blood thinner Pradaxa higher than first reported

The FDA's approval in 2010 of the blood-thinner dabigatran (Pradaxa) got many doctors excited. This drug got the green light after a head-to-head trial with warfarin (generic, Coumadin) in people with an irregular heart beat from atrial fibrillation.

Pradaxa was at least as effective as warfarin for preventing stroke-causing blood clots, and possibly caused fewer bleeding side effects. In addition, it is easier to use. Pradaxa doesn't require frequent blood tests, and isn't affected by food, like warfarin is.

"Clinicians in the United States are excited to have the first new oral anticoagulant in over half a century," said Dr. Richard Becker, Director of the Cardiovascular Thrombosis Center at Duke School of Medicine in North Carolina, in an interview with the medical journal Nature Reviews Drug Discovery. "This approval gives clinicians an opportunity to select therapies based on patient need."

Since then, studies of Pradaxa have slightly dampened the enthusiasm for the new drug. Take, for example, the results of a University of Pittsburgh survey of 9,400 men and women covered by Medicare. All had atrial fibrillation, an irregular heart rhythm that lets blood clots form in the heart. None had damaged heart valves. When these clots get into the bloodstream, they can cause strokes. In this group, 1,300 had been prescribed Pradaxa and 8,100 took warfarin. The researchers followed these men and women until they either stopped using the drug, switched to a different blood thinner, died, or until December 2011.

Among those taking Pradaxa, 9% experienced a major bleed, compared with 6% among those taking warfarin. The bleeding sites tended to differ. Bleeding in the stomach and intestines was slightly higher among Pradaxa users. Bleeding in the head was slightly higher among warfarin users. Black patients and those with chronic kidney disease were more likely to bleed from Pradaxa. The results were reported online in the journal JAMA Internal Medicine.

Reducing stroke risk from atrial fibrillation

For decades, the best way to prevent stroke from atrial fibrillation was by taking warfarin (Coumadin). But warfarin is a kind of "Goldilocks" drugs. You need regular blood tests to make sure the amount in your blood isn't too high (which puts you at risk of bleeding) or too low (which puts you at risk of having a stroke). You also need to pay attention to what you eat, because a sudden meal with a lot of vitamin K can counteract warfarin.

Then came Pradaxa. After doctors had been prescribing it for a while, they noticed that it was causing more episodes of major bleeding than had been expected. The FDA ordered that additional studies be performed on the safety of Pradaxa in the real world.

Some studies, like the one from, the University of Pittsburgh, showed a higher bleeding risk with Pradaxa than with warfarin. Other studies show the opposite.

FDA approves other blood thinners

Since 2010, two other blood thinners have been approved to prevent strokes in people with atrial fibrillation and no heart valve problems: apixaban (Eliquis) and rivaroxaban (Xarelto). Post-approval studies on the safety of these drugs are still ongoing.

One downside of the three new drugs: they are much more expensive than warfarin. One upside: none require regular blood tests to adjust the dose. One big unknown: the long-term side effects.

Choosing the right blood thinner

How do you and your doctor decide which drug is right for you if you have atrial fibrillation? There is no right answer. Here are the questions I ask my patients:

• Is cost an issue? If yes, warfarin will be the likely choice.
• Are you sure you will take the medicine as prescribed? This is important for all drugs. But warfarin stays in the body longer, so you have a longer protection time if you miss a dose. That isn't the case with the other three.
• Is it relatively easy for you to get a blood test? If the answer is no, then one of the newer drugs might be better.

I usually start my patients with atrial fibrillation on warfarin. I do this mainly because I take a conservative approach to new drugs. Also I have many years of experience with warfarin. If the patient has trouble keeping his or her warfarin levels in the proper range, I then consider switching to one of the newer drugs.

I might start with a newer blood thinner in a person a higher-than-average risk of bleeding into or around the brain. Examples include a person with:

• uncontrolled high blood pressure
• previous bleeding inside the head
• a family member who has had episodes of bleeding inside the head
• excessive alcohol use.