When it comes to blood thinners to prevent blood clots and reduce the risk of stroke, there is a new kid on the block. The brand name is Pradaxa but the drug is dabigatran etexilate mesylate. The most important question is: is Pradaxa a safe alternative to Coumadin (also called warfarin)?
Blood thinners are prescribed to people with heart or blood vessel diseases, or whose blood doesn’t flow well to the brain. Some people take a blood thinner for a very short time (usually heparin), and some people must take blood thinners regularly for years. For instance, people with an abnormal heart beat caused by atrial fibrillation are at a much higher risk of stroke than other people, and often take blood thinners their whole life. Atrial fibrillation, the most common cause of an irregular heartbeat, is a condition where the two upper chambers of the heart don’t contract normally.
Aspirin is also a blood thinner, but it works differently from prescription blood thinners like Coumadin. Aspirin keeps blood cells from clumping together (antiplatelet) while Coumadin lengthens the time (anticoagulant) it takes for a blood clot to form. Those who have atrial fibrillation and are at low risk for stroke may be prescribed aspirin. Aspirin poses less bleeding risks than Coumadin, but is usually not as effective for patients with atrial fibrillation. 1
How is Pradaxa different from Coumadin?
Like Coumadin, Pradaxa is an anticoagulant but it is also what is called a “thrombin inhibitor.” Both Coumadin and Pradaxa are supposed to reduce clotting, but not stop it completely. Stopping clotting completely can lead to excessive bleeding.
Pradaxa is only approved for use in patients with non-valvular atrial fibrillation, the most common type of atrial fibrillation. 2 Coumadin, on the other hand, is approved for the prevention and treatment of several health issues in addition to atrial fibrillation. These include pulmonary embolism (blockage of an artery in the lung) and venous thrombosis (blood clot in a vein). Additionally, Coumadin is sometimes prescribed to patients who have had a heart attack in order to prevent another heart attack. 3
Dose: Coumadin comes in several different doses. While this can cause some confusion, it also allows doctors to prescribe the dose that is best for a particular patient, based on age, weight, and other health factors. In the U.S., Pradaxa is available in only two doses, taken twice a day: 75 mg and 150 mg. The 75 mg dose is prescribed for those with kidney problems and is less effective in preventing stroke than the higher doses. In other countries, a 110 mg dose (also taken twice a day) is also available. This “in-between” dose appears to offer a lower bleeding risk while still being effective. Experts question why the FDA did not approve the 110 mg dose for sale in the United States, since it has the potential to be safer for some people than the 150 mg dose.4
Overdose and Bleeding: Coumadin interferes with your body’s ability to use vitamin K (found in many foods, including leafy greens), which your body needs to form clots and prevent excessive bleeding. This is why patients experiencing excessive bleeding due to a Coumadin overdose are given Vitamin K.5 Pradaxa works slightly differently from Coumadin. Those considering taking Pradaxa should know that there is no Vitamin K equivalent for this drug. If a person taking Pradaxa experiences excess bleeding (blood in stool, urine, coughing up blood or what looks like coffee grounds, small red spots under the skin), there is nothing that can undo or reverse its effects!6 That can be deadly.
Anticoagulants rank among the riskiest drugs on the market. However, certain anticoagulant drugs carry a higher bleeding and death risk than others. In a report monitoring adverse events for anticoagulants, it was found that bleeds associated with Pradaxa use were 5 times more likely to end in death than bleeds from Coumadin. 7 This may be influenced by the fact that there is no reversal agent for Pradaxa so once someone starts to bleed excessively it is very difficult to save them.
Blood Monitoring: A study published in 2014 looking at patients with atrial fibrillation taking Pradaxa found that the ones who suffered a stroke or major bleeding had much higher concentrations of Pradaxa in their blood.8 The study used both the 110 mg. dose available outside of the U.S. and the 150 mg. dose used in the U.S. How patients metabolized the drug ended up being much more important than the difference between the two doses. The huge range in blood concentration levels was just as large for each dose. The women in the study had Pradaxa blood concentrations 30% higher than the men, and people 75 and older had concentrations 68% higher than in people under 65.8 The researchers suspect that the high blood concentrations of Pradaxa in older people are the result of their kidneys not working as well, making it harder for them to clear the drug from their bodies. These findings suggest that, until tests are available to predict how people will metabolize Pradaxa, older patients and others may need to take doses even lower than 110 mg. or take their doses less frequently.
People taking Coumadin have to have their blood monitored regularly to make sure it is not becoming dangerously thin, since that could result in bleeding. Patients see Pradaxa as more convenient because they don’t need to get their blood monitored; this convenience can increase sales. This supposed benefit, however, presents risks: people who get their blood monitored regularly can find out if their blood has become too thin before it becomes a medical emergency. Without blood monitoring, a bleeding complication may be detected when it is too late to do anything to save the patient. Earlier this year, documents from the drug manufacturer, Boehringer Ingelheim, were released by a federal judge in response to thousands of lawsuits filed by users of Pradaxa and their families. According to experts who have seen these documents, Boehringer Ingelheim employees have expressed concern that the company’s own research shows that people may benefit from blood monitoring while on Pradaxa. 9 This raises serious questions about the safety of Pradaxa and whether the lack of blood monitoring is beneficial and safe for all patients.
Since Pradaxa’s approval in 2011, thousands of Pradaxa patients around the world have suffered serious and sometimes fatal bleeding. In July 2014, 4 articles published in the British Medical Journal (BMJ) described the risks of Pradaxa and reported that Boehringer Ingelheim held back important information during the review of Pradaxa’s clinical trials by the FDA and the European Medicine Agency (EMA – the European equivalent of the FDA).10 11 12 13 The withheld information showed that the company knew that monitoring patients’ plasma levels of the drug and adjusting the dose accordingly could have reduced the drug’s bleeding risk. However, Pradaxa’s biggest selling point was the convenience of not needing the blood monitoring required for Coumadin (warfarin). The BMJ articles point out that if monitoring had been required or recommended, Pradaxa would have lost its marketing advantage.
The research article in BMJ by Thomas Moore and his colleagues describes FDA’s approval process for Pradaxa as troubling from the start. Initially, the FDA refused to review the data for Pradaxa because there were inconsistencies and concerns about how well the data from the trial were collected. The authors also point out that the EMA currently makes tests and different doses of Pradaxa available to help make European patients safer. In contrast, the FDA has not provided patients in the U.S. with a plasma level test or the option of different doses.13
Dietary Restrictions: People taking Coumadin are advised not to eat excessive amounts of foods high in Vitamin K, because Vitamin K can decrease the effectiveness of Coumadin. Additionally, those taking Coumadin should avoid or limit alcohol as it can increase the effectiveness of the drug which may result in excessive bleeding. If you are taking Pradaxa for your atrial fibrillation, you don’t need to worry about whether your foods have Vitamin K or not. While Pradaxa does not require dietary restrictions, you should talk to your doctor about using alcohol if you are taking this drug.
Cost: Pradaxa costs around $3,000 per year while Coumadin usually runs about $200 per year. Coumadin requires blood test monitoring which does involve some additional cost, but it still will not cost as much as treatment with Pradaxa.
|Prevents clotting for those with atrial fibrillation||Yes||Yes|
|Reliable reversal agent available||No||Yes|
|Requires routine blood monitoring/testing||No||Yes|
|Approved for other indications (post heart attack)||No||Yes|
|Dosage availability||2 doses available in the United States.||Dosage determined by blood test. Several doses exist.|
The Bottom Line:
Pradaxa is an option for those with non-valvular atrial fibrillation, but it comes with several serious risks. Anyone thinking about taking this drug should consider the following:
•Pradaxa is not more effective at preventing strokes than its competitor, Coumadin.
•Pradaxa does not require blood test monitoring by a physician. But the company’s own data shows that being monitored could decrease your risk for complications.
•As with Coumadin, bleeding can occur with Pradaxa. The most serious bleeding would include gastrointestinal and bleeding of the brain, and is life-threatening.
•There is no known medicine or substance to reverse excess bleeding due to using Pradaxa.
•The 110 mg dose of Pradaxa, which is not available in the U.S. but is available in other countries, is less likely to cause excess bleeding than Coumadin and the 150 mg dose of Pradaxa.
All articles on our website have been approved by Dr. Diana Zuckerman and other senior staff.
- Sabir, I. N., Matthews, G. K., & Huang, C. H. (2013). Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice. Postgraduate Medical Journal, 89(1052), 346-351. doi:10.1136/postgradmedj-2012-131386 ▲
- (2013). Pradaxa prescribing information. Retrieved from http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf ▲
- (2011). Coumadin prescribing information. Retrieved from http://packageinserts.bms.com/pi/pi_coumadin.pdf ▲
- Eikelboom, J. W., Wallentin, L., Connolly, S. J., Ezekowitz, M., Healey,J. S., Oldgren, J., Yang, S., Alings, M., Kaatz, S., Hohnloser, S. H., Diener, H., Franzosi, M.G., Huber, K., Reilly, P., Varrone, J., Yusuf, S.Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation:The RE-LY trial. Circulation. 2011; 123: 2363-2372. ▲
- Fiumara K., Goldhaber S.,Z. Cardiology patient pages: A patient’s guide to taking Coumadin/warfarin. Circulation. 2009;119:e220–e222. ▲
- Kalus, J. S. (2013). Pharmacologic interventions for reversing the effects of oral anticoagulants. American Journal of Health-System Pharmacy, 70(10), S12-S21. doi:10.2146/ajhp130041 ▲
- Institute for Safe Medical Practices (2012). Quarter Watch. Retrieved from http://www.ismp.org/quarterwatch/pdfs/2012Q2.pdf ▲
- Reilly, P. A., Lehr, T., Haertter, S., Connolly, S. J., Yusuf, S., Eikelboom, J. W., & … Wallentin, L. (2014). The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: The RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). Journal of The American College Of Cardiology (JACC), 63(4), 321-328. doi:10.1016/j.jacc.2013.07.104 ▲
- Moore, K. (2014). Study of drug for blood clots caused a stir, records show. Retrieved from http://www.nytimes.com/2014/02/06/business/study-of-blood-clot-drug-pradaxa-unnerved-its-maker-documents-suggest.html?ref=health&_r=0 ▲
- Cohen D. Dabigatran: how the drug company withheld important analyses. BMJ 2014; 349:g4670 ▲
- Cohen D. Concerns over data in key dabigatran trial. BMJ 2014; 349:g4747. ▲
- Charlton B, Redberg R. The trouble with dabigatran. BMJ 2014; 349:g4681. ▲
- Moore TJ, Cohen MR, Mattison DR. Dabigatran, bleeding, and the regulators. BMJ 2014; 349:g4517 ▲