Substitutes for Coumadin in Atrial Fibrillation

The most feared complication of atrial fibrillation — and one of the most common cardiac arrhythmias seen in older people — is stroke. Stroke occurs because blood clots tend to form in the atrial chambers of the heart in people who have atrial fibrillation. These clots can break free and travel to the brain, thus producing a stroke.

• Read all about atrial fibrillation.

For this reason, it's recommended that most people who have atrial fibrillation be treated with anticoagulants, or blood-thinners, to reduce the risk of stroke. And until recent years, this has meant that many patients with atrial fibrillation had to take Coumadin (warfarin).

• Read about preventing stroke in atrial fibrillation.

Using Coumadin safely and effectively is often a challenge. The "correct" dosage of Coumadin can vary quite a bit from patient to patient, and — depending on several factors, such as what food you eat and what medications you take — can vary quite a bit in the same patient from week to week. For this reason, it is often necessary for patients on Coumadin to have frequent blood testing to measure their coagulation status (the "thinness" of the blood), and frequent dosage adjustments to keep their coagulation status in the correct range. This procedure is inconvenient to say the least, and the inconvenience leads to frequent "lapses" which, in turn, means that often patients taking Coumadin will have periods of time during which their blood is too thin (which can increase the risk of serious bleeding), or not thin enough (which can increase the risk of stroke).

The problems doctors and patients commonly experience with Coumadin have led drug researchers to search for oral substitutes for Coumadin: pills that produce an anticoagulation effect without requiring frequent blood tests and dosage adjustments. After many years of effort, this research has now borne fruit. Three such Coumadin substitutes are now approved by the US Food and Drug Administration for patients with atrial fibrillation not associated with heart valve disease. These drugs are dabigatran (Pradaxa, approved October, 2010), rivaroxaban (Xarelto, approved November, 2011), and apixaban (Eliquis, approved December, 2012).

All three of these new drugs produce a stable anticoagulant effect with standard dosages, so no blood tests or dosage adjustments are required. And studies have suggested that with all three of the new drugs, the magnitude of stroke reduction in atrial fibrillation is at least as strong as with Coumadin. Further, in clinical trials, the risk of major bleeding complications with these newer drugs has been no higher — and in fact appears to be lower — than with Coumadin.

What Are The Drawbacks To the New Drugs?

There are disadvantages to the newer anticoagulants, however. Perhaps the chief disadvantage is that, in contrast to Coumadin, no antidote is currently available for any of these new drugs — that is, no drug is available that rapidly reverses their anticoagulant effects. This means that if a major bleeding episode does occur, the potential for a bad outcome may be higher with the new drugs than with Coumadin. (This fear, for dabigatran at least, has been somewhat relieved with the most recent evidence.) Antidotes which can reverse the anticoagulant effects are in development for all three of these new drugs, but it's not clear when (or even whether) they will become available.

Also, since these drugs are indeed quite new, it's relatively likely that as they come into widespread usage, some new, currently unidentified side effects may become apparent. (This is a risk one takes, of course, with any relatively new drug.) Finally, in contrast to Coumadin (which can be taken once a day), dabigatran and apixaban must be taken twice a day. Rivaroxaban is a once-a-day drug.

Which Drug Should Your Doctor Prescribe If You Have Atrial Fibrillation?

So if you have atrial fibrillation, which anticoagulant drug should you be given? Frankly, this is a question which medical experts are just now sorting out. But because of the well-known drawbacks of Coumadin, most experts are leaning fairly strongly towards recommending the newer anticoagulant drugs as the first choice in patients with atrial fibrillation not associated with valvular heart disease.

Patients with atrial fibrillation will probably find their doctors recommending one of the new drugs if they're being started on anticoagulation for the first time, if they've had difficulty maintaining a stable dose of Coumadin, or if (after listening to the potential risks and benefits of all the choices) they themselves express a clear preference for the newer drugs. On the other hand, patients who've been taking Coumadin successfully — with stable blood tests on a stable dosage — for a few months or longer are probably better off sticking with Coumadin.

At this point, there is little objective evidence for choosing one of the newer anticoagulant drugs over another. So for the time being, this decision is likely to be based on such things as the relative costs of these three drugs. As more clinical experience is gained with the new drugs, it is entirely possible that one of them will prove to be more advantageous (or more disadvantageous) than the others for specific categories of patients with atrial fibrillation. For instance, since dabigatran is excreted largely by the kidneys, it is not the best choice for people with kidney disease.

In summary, all three of these new anticoagulants appear to be attractive alternatives to Coumadin. However, the facts that no antidote is available for any of them, and that clinical experience with all three is limited, mean that doctors and patients deciding on the "right" therapy for atrial fibrillation ought to carefully weigh the risks, the benefits — and the unknowns — of all these choices before making their decision.

_Sources:

_{Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139.}

_{Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883.}

_{Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365:981.}

_{Furie KL, Goldstein LB, Albers GW, et al. Oral Antithrombotic Agents for the Prevention of Stroke in Nonvalvular Atrial Fibrillation: A Science Advisory for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2012.}