I Have Atrial Fibrillation: Which New Blood Thinner Should I Take?
By T. Jared Bunch, MD
Published Nov 19, 2013
Today at the American Heart Association meetings in Dallas, the results of the Engage AF TIMI 48 trial were presented. This was a large trial that essentially evaluated a new drug therapy to prevent stroke in patients with atrial fibrillation.
Atrial Fibrillation and Stroke
Atrial fibrillation is an abnormal heart rhythm that results in loss of active squeezing of the upper heart chambers. As such, blood flow slows and clots can form. These clots can then be injected to the body organs, and if they go to the brain a stroke develops.
For many years, one drug was the proven therapy for stroke prevention in patients with atrial fibrillation. This drug is called warfarin (Coumadin). Warfarin is an anticoagulant or blood thinner. The drug doesn’t actually make the blood thinner; it makes it less likely to form a clot. Warfarin works by blocking our body’s ability to recycle vitamin K. Vitamin K is used in many of the small proteins that come together to create a clot. With less vitamin K around in our bodies, there are less of these proteins available and as a consequence it takes the body longer to form a clot.
Warfarin is a tough drug to take long term. In previous studies around 30% of people will stop taking it. It requires frequent blood tests to regulate the dose. Warfarin also has many interactions with other drugs, herbs, and food sources. Diets often are modified to minimize the amount of vitamin K consumed and make the drug’s effect in the body more predictable. For over 20 years there has been extensive efforts to replace warfarin with other drugs. Many drugs have come and gone as they were either not as effective or were more hazardous than warfarin. Over the past 3 years new safer drugs have emerged. These drugs are called novel oral anticoagulants (NOACs). Where we have not had good alternatives for warfarin in the past, we now have 4 that have come available all in a short period of time. This is a great benefit for patient care, but at the same time it leads to confusion as to which drug should be used.
Novel Oral Anticoagulants
The new drugs are called dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Lixiana). The trade names are those in parenthesis. Edoxaban was the most recent drug studied and was the subject of the Engage AF TIMI 48 trial (4).
First, your insurance provider will have a direct say into which drug you take. One or two of these new drugs may be approved for your use. In this regard, realize that all of these drugs are at least as good as warfarin for preventing stroke and all are better than warfarin in reducing your risk of serious bleeding in the brain. All of these products are not reversible, similar to warfarin, and if you are bleeding the use of blood products and other measures may be required to help your body stop. However there are some important differences to consider.
Dabigatran (Pradaxa) was the first drug that was available in the United States. Dabigatran comes in two doses in the United States, 150 mg twice daily or 75 mg twice daily. Dabigatran was not only equal to warfarin, but it proved to be superior to it in preventing stroke in the RELY trial (1). Bleeding rates in the head were lower with dabigatran. However, bleeding from the stomach or bowels was higher. The most common side effect was dyspepsia, which is a term used to describe stomach pain. Dyspepsia was relatively common occurring in approximately 11% of people. The lower dose available in the United States is for people that have moderate kidney dysfunction. It is important to know that the lower dose was not formally used in the RELY study. Without a large body of clinical evidence to support the use of the lower dose and understand potential risks, I do not use it.
Rivaroxaban (Xarelto) was the second drug available in the United States. Rivaroxaban comes in two doses, 20 mg daily or 15 mg daily. In the Rocket AF trial, rivaroxaban was at least as good and tended to be better than warfarin at preventing stroke (2). Rivaroxaban also significantly lowered the risk of bleeding in the brain and head. Bleeding in other locations was slightly higher with rivaroxaban compared to warfarin. The lower dose is for people that have moderate kidney dysfunction. This dose was actively studied in the trial and found to be both effective and safe.
Apixaban (Eliquis) was the third drug to become available in the United States. Apixaban comes in two doses, 5 mg twice daily or 2.5 mg twice daily. In the Aristotle trial, apixaban was at least as good and tended to be better than warfarin at preventing stroke (3). Similar to the other drugs, risk of bleeding in the brain and head was lower. However, this drug was unique in that bleeding from other sites including the stomach, bowels, and bladder was less. Overall, apixaban due to better efficacy and lower bleeding improved survival significantly compared to warfarin. Apixaban is the only drug that can claim that survival improved with its’ use compared to warfarin. The lower dose is for people that have moderate kidney dysfunction. This dose was actively studied in the Aristotle trial and found to be both effective and safe.
Edoxaban (Lixiana) was the drug presented today and is not currently available in the United States. In the Engage AF TIMI 48 trial two doses were studied (60 mg and 30 mg daily) (4). This was a huge trial of 21,026 patients with follow-up of over 3 years in many patients. The higher dose of edoxaban was at least as good and tended to be better than warfarin at preventing stroke, however the lower dose was not as good as warfarin. Cranial or head bleeding was better with both the higher and lower doses of edoxaban compared to warfarin. Bleeding from the stomach was greater than warfarin with the higher dose of edoxaban and lower than warfarin with the lower dose of edoxaban.
Which Drug Should I Take?
Here are a few things to consider with attached recommendations.
If you have trouble taking drugs twice a day and often miss a dose, then you should use rivaroxaban or if it becomes available, the higher dose Edoxaban. Unlike warfarin these drugs quickly leave your body. You have to be very compliant with the dosing schedule or you will be at higher risk for a stroke.
If you have stomach pains or heart burn, then you should consider a drug other than dabigatran
If you are most concerned about stroke and less worried about bleeding then dabigatran was the only drug that was superior (not equal or slightly better) than warfarin in preventing stroke
If you are worried about bleeding or have experienced bleeding from the stomach, bowels, or bladder then apixaban is the better choice once you are cleared by your physician to use a blood thinner
If you want the drug that will, because of both its’ benefits and risks, help you live longer compared to warfarin then apixaban is your choice
If you have moderate kidney dysfunction then consider apixaban or rivaroxaban since these two drugs have reduced doses available that are well studied and found to be effective and safe
If you have used warfarin for years and rarely if ever have to change your dose and you have not experienced adverse symptoms then continue your warfarin.
I am hopeful with the many anticoagulation options in a competitive market the cost of these drugs will decline. As mentioned before, all of these drugs reduce stroke at rates nearly equal or better than warfarin and all reduce brain bleed risk. For the first time in decades, warfarin has significant competitors that will help us as physicians prevent one of the most devastating complications with atrial fibrillation, stoke.