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I am a clinical pharmacist currently doing freelance writing on various pharmacy topics. I graduated from Arnold and Marie Schwartz School of Pharmacy in 1988 with a bachelors degree in pharmacy. While practicing as a clinical pharmacist I obtained my Doctor of Pharmacy degree (PharmD) from the University of Florida in 2003.

Thursday, February 7, 2013

Eliquis®, Pradaxa®, Xarelto®: Which Blood Thinner to Use?

Eliquis®, Pradaxa®, Xarelto®: Which Blood Thinner to Use?
With the recent approval of Eliquis® (apixaban) in most major countries for the prevention of stroke and systemic embolism (blood clots throughout the body) in patients with nonvalvular (patient has normal heart valves) atrial fibrillation (AF- an abnormal heart rhythm), all 3 of the new oral anticoagulants will now be available for this indication, leaving doctors with the dilemma of which one to use in which patients. Being the first oral alternatives to warfarin, with all its limitations, these 3 new agents, the thrombin inhibitor dabigatran (Pradaxa®, Boehringer Ingelheim), and the 2 factor Xa inhibitors, rivaroxaban (Xarelto®, Bayer/Johnson & Johnson) and apixaban (Eliquis®, Bristol-Myers Squibb/Pfizer), are expected to revolutionize the field of stroke prevention in AF. But do these drugs really herald the end of warfarin, and how do doctors decide which of the 3 new agents to use? Medscape Medical News spoke to experts with quite different views of the situation. Alexander G.G. Turpie, MD, emeritus professor of medicine at McMaster University, Hamilton, Ontario, Canada, a thrombosis (clot) specialist, is very positive about the new agents, saying they have major advantages over warfarin and should be used in preference to warfarin in most cases. In contrast, Larry B. Goldstein, MD, professor of neurology at Duke Stroke Center, Durham, North Carolina, believes they should have a more restricted role for the time being. "I would say that they are a very reasonable option for patients who are compliant but cannot maintain a stable INR [international normalized ratio] on warfarin," he said. The INR is a blood test that measures how effectively warfarin is thinning the blood. The INR must be kept within a specific range. "But if a patient is stable on warfarin and is managing well with home monitoring, I don't think there is an overwhelming need to switch them." Dr. Turpie points out that although warfarin is very effective, it has many limitations, including the need for monitoring and regular dose adjustments, as well as many drug and food interactions. These interactions, he says, "are preventing around half the people who should be taking oral anticoagulants from receiving such therapy. "These new drugs overcome these limitations and should vastly increase the number of patients able to take oral anticoagulants," he said. "Most patients and doctors now want to use one of these new agents instead of warfarin." In addition to the practical advantages of the new drugs, they have a major clinical benefit in that all 3 new agents were associated with lower rates of intracranial hemorrhage (ICH-bleeding within the brain) compared with warfarin in clinical trials. Dr. Turpie says that this factor alone is enough for him to choose one of the new drugs in preference to warfarin. "Even when I think just about the 2500 patients in my clinic who are taking warfarin for life, I know that 1 in 300 of them will have an ICH per year no matter how well controlled they are," he said. "Now with the new drugs, this can be reduced to 1 in 500 to 600. That is a big deal." Dr. Goldstein agrees that this is a strong argument in favor of the new drugs, but he counters that the lack of an antidote also has to be considered. "That means if an ICH does occur, there may be no way to stop it." Dr. Turpie would like to prescribe these new drugs for most of his patients with AF. "There are obvious exceptions, such as those patients with mechanical heart valves in whom they are contraindicated," he notes, but apart from this the major deciding factor for him will be the patient's ability to pay. "I will suggest one of these new drugs for my new patients, and when my existing patients come in for a review I will suggest they switch if they can afford it," he said. He adds that the patients themselves are also very keen to take one of the new agents. "Many patients are not waiting for a review and are coming in and asking for the new drugs." He believes warfarin has only a limited role now. "It is still needed for heart valve replacement patients and it will still be used in severe rheumatic valvular disease as there are no data on the new agents yet, but I think its time is over in AF."
Dr. Goldstein, however, is far more cautious. He says he understands the urge to use these new drugs extensively given the positive clinical trial results, but he cautions that there are many complex issues to be considered. "None of the studies had very long follow-up, so long term use of these agents is still somewhat of an unknown, and most clinicians know that drugs need to be out in the big wide world for a while before we know everything about them," he told Medscape Medical News.
He pointed out that although a main advantage of the new agents is the lack of requirement for monitoring because they are used at a fixed dose, this also has a flip side. "It means that we don't know if patients are actually taking their drugs," he says. If they are on warfarin we can assess their blood coagulation (blood clotting) levels with a simple blood test, but this is not possible with the new drugs."
He added that this is slightly easier with Pradaxa® than with the factor X inhibitors (Xarelto® and Eliquis®) because Pradaxa® increases clotting time, which can be tested. Whether this correlates with Pradaxa®'s clinical effect is unknown. But there is no test for Xarelto® and Eliquis®. "So while the monitoring of warfarin is a nuisance, it does mean the patient is having regular contact with a medical professional, which helps with adherence." "Patients are at increased risk of an embolic (clotting) event even if they just miss one dose of these new agents. I have personally seen this happen," he said. "This is a big issue, especially as these drugs will be used by a relatively elderly population. Doctors really have to drum this home to their patients. Whereas with warfarin, missing one dose probably wouldn't have much effect." He adds that the cost of the new agents will exacerbate this problem. "These drugs are expensive. I worry that some patients may say they can afford them and start taking them and then decide not to continue because of the cost and not tell their doctor, so put themselves at a large increase in risk of stroke." Dr. Turpie and Dr. Goldstein have different views on the bleeding risks with the new agents and the fact that no antidotes are available as yet. Dr. Turpie says he is "not too worried" about these issues. "The regulatory agencies seem happy with the bleeding data," he said. "It is well known that doctors report side effects more rigorously with new drugs. We see bleeding with warfarin all the time but don't often report it." But Dr. Goldstein believes the lack of an antidote is a problem. "While these drugs  effects will wear off relatively quickly, this is not sufficient when a patient is bleeding into the brain or is experiencing another type of life-threatening bleed. You just can't wait for it to stop under those circumstances. " So, having decided that your patient is a good candidate for one of the new agents, how do you to choose which one to go for? On the basis of clinical trial data, all 3 new agents seem to have advantages over warfarin. But they have somewhat different profiles. Dr. Goldstein noted that although all 3 showed a reduction in ICH versus warfarin, Pradaxa® was the only one that actually showed a significant reduction in thrombotic stroke; Eliquis® was the only one that showed a mortality (death) reduction and a reduction in major bleeding. Gastrointestinal bleeding (bleeding in the stomach and intestines) was increased with Pradaxa® and Xarelto® but was not significant with Eliquis®. Other issues that need to be considered include the dosing schedule. Xarelto® has the advantage of a once-daily dose, whereas Pradaxa® and Eliquis® are given twice daily. Dr. Goldstein pointed out that renal insufficiency (decreased kidney funtion) is an issue with all 3 new drugs, and they all need to be modified if kidney function is low, whereas warfarin can be used in patients with renal failure (patients whose kidneys have completely failed). In terms of which drug to select, Dr. Goldstein said, " I think you have to look at all the nuances from the trials and select the drug that is most appropriate for each individual patient. "Things to consider are will they be compliant, will once a day be much more preferable to twice a day, what other drugs are they taking, do they have issues with bleeding or GI [gastrointestinal] problems, and can they pay for the drugs. The doctor needs to have a long conversation with the patient about all these issues before deciding if any of these drugs are suitable and then which one " Dr. Turpie believes all 3 drugs are very similar, and most of the differences seen in the clinical trial results are due to differences in trial design, numbers, and patients recruited rather than the drugs themselves. "I would say that if a patient has renal insufficiency (low kidney function) or is prone to GI side effects, then either Xarelto® or Eliquis® may be a better choice than Pradaxa®."The bottom line is you must have a good discussion with your healthcare practitioner to decide which blood thinner is best for you as an individual patient.

Source: Medscape Medical News


  1. can you take omega oils with these medications//I
    AM ON PRADAXA at the moment.

  2. You must speak to your healthcare practitioner before taking omega oils if your are on medications like Pradaxa. Pradaxa is a blood thinner and makes you more susceptible to bleeding. Omega oils have a similar effect, so they can further increase your chance of bleeding. Please check with your doctor first before you take ANY supplements if you are on medications like Pradaxa.


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