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New alternatives to warfarin

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“Most experts would argue that from a safety perspective, for the things you really care about, these new drugs are much better than warfarin.”
-Dr. Christian Ruff
Brigham and Women’s Hospital

New drugs may be best when starting treatment for atrial fibrillation, but don’t switch if warfarin works for you.

Is it time to say goodbye to warfarin (Coumadin)? The answer depends on how well you and warfarin get along, and on whether you’ve ever met.

For almost 60 years, doctors have prescribed warfarin to prevent stroke-causing blood clots in people with atrial fibrillation. It’s been around this long for a very good reason: it works quite well for many people, says Dr. Christian T. Ruff of Harvard-affiliated Brigham and Women’s Hospital. But that’s not the whole story.

“It is one of the most difficult and dangerous drugs in clinical practice,” Dr. Ruff notes. “If you look at patients who started on warfarin, after a period of time nearly half are not taking it or are not in the therapeutic range of coagulation.” That range is between 2 and 3 on the international normalized ratio (INR) test, a measure of blood-clotting speed. People who are not in this narrow therapeutic range will overshoot or undershoot their blood-clotting targets. Overshooting makes them prone to bleeding problems, while undershooting increases the likelihood of developing a potentially dangerous blood clot.

In 2010, the FDA approved the first warfarin alternatives for people with nonvalvular atrial fibrillation: dabigatran (Pradaxa) and rivaroxaban (Xarelto). A third, apixaban (Eliquis), was approved in 2012. Now there are choices for people newly diagnosed with atrial fibrillation, as well as for those already taking warfarin.

New drugs gaining popularity

Warfarin is in a class of drugs called anticoagulants, which inhibit a major arm of the blood-clotting process. The three new anticoagulants target different parts of the coagulation process.

The goal of anticoagulant therapy is to slow the clotting process enough to prevent dangerous clots, but not so much that there is dangerous internal bleeding. This requires a delicate balance.

A major problem with warfarin is that it’s hard to find the right balance. Many common drugs, foods, and dietary supplements affect how well warfarin works. Depending on these and other factors, the same dose of warfarin may have too much or too little anticoagulant effect at different times.

This is why people taking warfarin must get regular INR clotting tests, says Dr. Daniel E. Singer, professor of medicine at Harvard Medical School.

Constantly hitting the INR target isn’t easy, and that’s one reason why the new anticoagulants now are being prescribed more often than warfarin among people starting treatment with a new or different anticoagulant.

Yet many doctors prefer to wait until they’re sure these newly approved drugs don’t cause unexpected long-term side effects, says Dr. Singer, who has consulted for all three of the companies making the new anticoagulants.

Warfarin is ahead of all the new drugs in one major measure: it costs a lot less. Even with the costs of extra INR testing factored in, the new agents are about 30 times more expensive. Public and private insurance makes the new drugs affordable for many people—but increased use of these expensive brand-name drugs adds to the nation’s health care costs.

New drugs more effective?

Warfarin works very, very well. It reduces strokes from blood clots by more than 60%. “That is pretty staggering,” Dr. Ruff says.

Yet the new anticoagulants may work even better. “Across the board, these new oral anticoagulants seem more effective,” says Dr. Sebastian Schneeweiss, professor of medicine at Harvard Medical School.

But most of the data on how well these new drugs prevent stroke come from clinical trials. People enrolled in clinical trials tend to take their medications more regularly than people do in the real world.

“The new agents are much shorter-acting. If you miss one, two, or three doses, you have no anticoagulation,” Dr. Ruff says. “One thing about warfarin is even if you miss a dose or two, you will still have enough blood thinner in your system.”

New anticoagulants safer

The most worrisome side effect of anticoagulants is a direct result of the way they work: slowing blood clotting makes bleeding more likely.

“The new anticoagulants are as bad or worse for most kinds of bleeding, especially gastrointestinal bleeding, but they have this really nice feature—they reduce the risk of bleeding into or around the brain by 33% to 50%,” Dr. Singer says. “That’s the showstopper as far as doctors and patients are concerned. These intracranial bleeds are relatively rare, but they are the most devastating toxicity of anticoagulants.”

Don’t switch if warfarin works

There is one safety issue where the new drugs fall short of warfarin. Because of the risk of bleeding, emergency surgery is much more dangerous for patients taking anticoagulants. There’s an antidote for warfarin—a dose of vitamin K—that largely blocks the drug’s anticoagulant effect. But with the new agents, doctors simply have to wait for the drugs to wear off.

Over all, Dr. Ruff says, the new drugs have a better safety profile.

“There are side effects—it is not a free lunch,” he says. “But most experts would argue that from a safety perspective, for the things you really care about, these new drugs are much better than warfarin.”

Because of the safety and effectiveness of the new drugs, anyone beginning anticoagulant treatment for atrial fibrillation should talk with his or her cardiologist about whether the new anticoagulants are worth the cost.

Posted by: Dr.Health

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