News Review From Harvard Medical School -- Slightly More Heart Attacks with Pradaxa
People who take a newer blood thinner to prevent strokes may have a slightly higher risk of heart attack, a review of research finds. The overall heart attack rate was small, however. The new review combined results of 7 prior studies. The studies included 20,000 people who used dabigatran (Pradaxa). They were compared with about 10,500 people who used older drugs, warfarin (Coumadin) or enoxaparin (Lovenox). Everyone in these studies had atrial fibrillation. This is a heart rhythm problem that increases formation of blood clots. People were taking blood thinners to prevent strokes caused by a clot. Among those taking dabigatran, 1.2% had a heart attack or had chest pain that occurred with little exertion. For those taking the other drugs, the rate of these heart events was 0.8%. Drug companies have been working to develop alternatives to warfarin because it's difficult to maintain the right dose of this drug. People need frequent blood tests and changes in their dose. The wrong dose can cause bleeding or fail to prevent strokes. The journal Archives of Internal Medicine published the study. HealthDay News wrote about it January 9.
By Mary Pickett, M.D.
Harvard Medical School
What Is the Doctor's Reaction?
Warfarin (Coumadin) is a commonly used clot-prevention drug. These drugs are also called anticoagulants or blood thinners. There has been great enthusiasm for a new family of drugs that can be used instead of warfarin. But what does the news this week advise us to do? Curb our enthusiasm.
Researchers have been counting up heart attacks and other heart events in people who take a new drug and people who take older drugs. The old drugs include either warfarin or another clot-preventing drug, enoxaparin (Lovenox). The new drug is dabigatran (Pradaxa). From what they see now, these researchers say we need to know more about the new drug and its safety.
Most people use dabigatran because they have atrial fibrillation. This is a heart rhythm disturbance that slows the blood flow in the left atrium of the heart. Slow blood flow can allow a clot to form. If the blood clot travels to the brain, it can cause a stroke. People who have atrial fibrillation commonly use anticoagulant drugs to lower their risk for stroke.
The U.S. Food and Drug Administration (FDA) approved dabigatran in 2010. Just a few months later, expert groups updated their guideline about treatments for people with atrial fibrillation. The American College of Cardiology, the American Heart Association and the Heart Rhythm Society issued the new guideline. It gave patients the option to use either warfarin or dabigatran. It "rolled out a red carpet" for the new drug.
Warfarin is a tricky drug to use. It requires close monitoring with blood tests at least every three weeks to make sure the dose is correct. Some drugs and foods can temporarily cause warfarin to either be less effective than needed, or more hazardous. Even with frequent blood tests, only about 60% of patients can keep using the same dose after each check.
Dabigatran does not require frequent blood tests for monitoring. This is a huge advantage.
Laboratory costs are saved. However, the drug is very expensive. It costs about $10 a day. Some experts are worried that overdose or bleeding problems with dabigatran may also be harder to treat. That's because the effects of the medicine can't easily be reversed in an emergency. If warfarin has made the blood too thin, doctors can use vitamin K or neutralizing "binders" to reverse the effect. It is not as easy to reverse the effects of dabigatran.
The new concern about dabigatran is that studies appear to show a higher rate of heart attack with dabigatran than with warfarin or enoxaparin. People taking dabigatran also were more likely to have chest pain with little or no exertion.
It might not be fair to say this is a side effect of dabigatran. Some experts think that these studies might just show that warfarin and enoxaparin are better at preventing heart attacks. The total number of heart attacks was pretty low. But it is a difference that might make the new drug a bit less of a new favorite.
What Changes Can I Make Now?
If you take warfarin, a new drug might or might not be in your future. It is reasonable to wait a bit longer before you and your doctor consider a change to dabigatran or some other new drug. The safety details are still being worked out.
One change you might talk over with your doctor is the idea of testing your blood at home instead of a medical lab or doctors office. A home test fairly recently became available. It uses a meter to test a drop of blood. In the United States, only 1% of patients who take warfarin test themselves.
A recent article looked at 11 studies about the use of home monitoring. It combined their results, adding up to 6,400 patients. This study found that people who used home testing and office testing were equally likely to have bleeding problems from too much warfarin. But blood clot risk was reduced by a lot -- up to half -- for people who did home testing. Home testing for warfarin is both convenient and safe. We should use it more!
What Can I Expect Looking to the Future?
The FDA will give dabigatran close scrutiny because of this new worry about heart attack rates. It will stay on the market for now. Some of our most important information about drug safety comes from problems that we see and record among patients who are in the "real world," not in studies.
Another newly developed drug is similar to dabigatran. It is named rivaroxaban. Studies show that it reduces stroke risk from atrial fibrillation as well as warfarin and dabigatran. Rivaroxaban has not yet received FDA approval, so it is not on the market. The FDA may require more information about heart attack rates before it considers approval for rivaroxaban.