Coumadin, Eliquis, Pradaxa, Xarelto: Which anticoagulant is best for you?

Posted on: 08/05/2014

Koth Cassavaugh, Director of Pharmacy at Auburn Community Hospital (ACH), received his B.S. in pharmacy and his Pharm.D. from Albany College of Pharmacy. He is currently working with student Lauren Stummer, Wegman’s School of Pharmacy at St. John Fisher College, who is a Pharm. D. Candidate, Class of 2016. They provided answers for the following questions.

 

Q: How long has Coumadin been in use? What medical conditions is it used to treat, and how effective is it?

A: Warfarin (Coumadin) received FDA approval in 1954, although there have been many adjustments involving contraindications, warnings, and precautions to its label through the years. Coumadin in indiated for prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism. It is also indicated for prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Lastly, Coumadin is used to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events, such as stroke or systemic embolization after myocardial infarction. Coumadin is an anticoagulant that blocks the formation of Vitamin K, thus inhibiting the formation of clotting factors and protein that are dependent on Vitamin K. By inhibiting these clotting factors and proteins, Coumadin reduces the ability of blood to form clots and “thins” the blood. It is a very effective medication and has been shown to reduce patient mortality by 24%, reduce the risk of recurrent myocardial infarction by 34%, and reduce the risk of cerebrovascular events by 54%.

Q: What are the newer alternatives to Coumadin, and when were they approved?

A: The newer alternatives are Dabigatran (Pradaxa), approved in 2010; Rivaroxaban (Xarelto), approved in 2011; and Apixaban (Eliquis), approved in 2012.

Q: How do they differ from Coumadin in the way they work?

A: Eliquis, Xarelto, Pradaxa and Coumadin are all anticoagulants and inhibit clot growth and propagation by inactivating clotting factors, but they act on different steps in the clotting cascade. Eliquis and Xarelto are both Factor Xa inhibitors and Pradaxa is a Direct Thrombin Inhibitor. Thombin is an enzyme that facilitates the clotting of blood and Pradaxa acts directly on this enzyme, whereas Eliquis and Xarelto work on the clotting Factor Xa that precedes this enzyme in the clotting cascade. It is important to understand there is a clear distinction between the newer agents. They are often clumped on the assumption they are all one new class of drugs, but they are two distinct classes. This plays a role in not only the efficacy but also in the side effects. The direct thrombin inhibitor should not be considered the same as the Factor Xa agents or Coumadin.

Q: Please compare the new drugs to Coumadin in terms of benefits and possible dangers or side effects.

A: One advantage of the new oral anticoagulants compared to Coumadin is that they have a wider therapeutic window so they do not need individualized dosing. Coumadin dosing is very patient-specific and a lot of alterations need to be made to optimize therapy. The new anticoagulants also don’t require frequent blood test (INR) monitoring, whereas Coumadin does. The blood tests for Coumadin are to make sure the patient’s INR isn’t too low (non-therapeutic) or too elevated, increasing risk for bleeding. Since the newer agents are generally continuously in a therapeutic range, they have been shown to be more effective than Coumadin at reducing the risk of stroke. Coumadin also interacts with more prescription medications. Since the new oral anticoagulants don’t need as much monitoring and have fewer drug interactions, they are much more convenient. Patients going on Coumadin have to make some lifestyle changes. You have to watch the amount of green leafy vegetables you consume (or try to make it consistent). Patients are often instructed to avoid a hard bristle toothbrush, watch alcohol intake, and a host of other lifestyle modifications to prevent issues with Coumadin. Compared to Coumadin, the new anticoagulants have limited prospective data since they are relatively new, and there is concern whether you can reverse the agents if there is a bleeding issue. Vitamin K has been shown to be effective in reversing Coumadin, and there is FDA approval for the use of Prothrombin Complex Concentrate (PCC), also known as KCentra, for rapid reversal. There are reports of Kcentra reversing the effects of Xarelto and Eliquis, but it is not yet FDA approved. Pradaxa does not currently have any known reversal agents available.

Q: As a pharmacist, do you recommend one specific drug as the best anticoagulant?

A: There is no one perfect agent for everyone, and there are differing opinions on this matter. If a patient has been on one agent without problems then there is no reason to switch. For new patients or ones who have been having problems with their current agent, I feel most patients should be started or switched over to one of the anti Xa agents. The newer agents are more expensive from a strictly drug cost perspective, but when you factor in the cost of the frequent INR monitoring, they may be more cost-effective. There is the concern with reversing the newer agents, but most hospitals have treatment guidelines for patients with active bleeding issues. I am often an advocate for the agents that are a once-a-day medication. As with all agents, they will not work if not taken as prescribed, and it is often easier to remember to take one pill a day. Factors the physician and pharmacist review when dispensing these agents include patient compliance, renal function, bleeding risk, and other medications the patient is taking. Based on these factors, I tend to recommend either Xarelto or Eliquis. Having a variety of choices helps tailor the treatment for specific patients.

Q: Can Coumadin, Pradaxa, Xarelto or Eliquis be used in combination with over-the-counter medications, herbal products, or vitamins?

A: Before taking an over-the-counter medication, herbal product or vitamin, I recommend talking to a physician or pharmacist. Many of these products interact with and reduce the efficacy of prescription medications. Some specific classes of medications to avoid while taking anticoagulants are antifungals (such as Ketoconazole) and NSAIDs (such as Ibuprofen and Naproxen), which may put patients at an increased risk of bleeding.

Q: If a patient experiences negative side effects from an anticoagulant, should he/she discontinue it?

A: The patient should contact a physician or pharmacist before completely discontinuing their medication. Rapid discontinuation puts the patient at an increased risk of stroke. The dose needs to be tapered off and an alternative therapy considered. If there is uncontrolled bleeding, the patient should get to an ER as soon as possible.

Q: Is cardiovascular disease under better control due to improved medications?

A: We have a wider variety of more effective medications. But with the increase in obesity and diabetes, cardiovascular disease is becoming more prominent.

Q: Please add anything you think should be included in this article.

A: I always advocate for patients to discuss any question or concern with their pharmacist. Please try to use only one pharmacy so the pharmacist can see all that has been prescribed for you. This will help the pharmacist ensure your safety by seeing if there are any possible interactions with any of the medications you are taking. I also advocate for patients to keep an up-to-date list of all the medications they take. Bring this to your appointments, the pharmacy, and/or the hospital so all healthcare workers have an understanding of what medications you are on.

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