New Anticoagulants Offer Promise, but Obstacles Remain


Dr. Hospitalist

I see more and more people taking one of the newer anticoagulants. I’ve also seen a few disasters with these drugs. What’s the story?

Stacy M. Harper, Green Bay, Wis.

Dr. Hospitalist responds:

Although warfarin (Coumadin) has been a mainstay anticoagulant for decades, it can often be a frustrating medicine to manage due to its myriad drug interactions and the constant need for therapeutic testing. Recently, we have seen new medications hit the market (with one more likely to be approved soon), each with its pros and cons. Here’s an overview:

  • Dabigatran (Pradaxa): It’s a direct thrombin inhibitor, taken twice daily. It has been approved for use in stroke prevention for atrial fibrillation (afib) (RELY trial) at 150 mg bid. It’s also been extensively studied for VTE prevention after orthopedic surgery, but it has not yet been approved in the U.S. for this indication.

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As with all of these drugs, there is no reversal agent and there are no levels to measure. A recent report noted an increased risk of bleeding in patients who are older, have a low BMI, or have renal dysfunction. The manufacturer recommends a dose of 75 mg bid for patients with renal dysfunction, defined as a GFR of 15 to 30 mL/min; however, that dosing regimen was never explicitly studied.

Overall, it’s become quite a popular drug with the cardiologists in my neck of the woods. GERD can be a bothersome side effect. I avoid using it in patients older than 80, or in a patient with any renal dysfunction. Also, remember that it is not approved for VTE prevention or treatment.

  • Rivaroxaban (Xarelto): An oral factor Xa inhibitor. Usually taken once daily at 10 mg for VTE prevention (RECORD trials). It is dosed at 20 mg/day for stroke prevention in afib (ROCKET-AF trial). Just recently, it was approved by the FDA for use in the acute treatment of DVT and PE (EINSTEIN trial), dosed at 15 mg BID for the first 21 days, and then continued at 20 mg daily after the initial period (see “Game-Changer,” p. 41). It is more hepatically metabolized than dabigatran, but it still has a significant renal clearance component. When compared to lovenox in orthopedic patients, it’s as effective but with a slightly higher risk of bleeding. I would avoid using it in any patients with significant renal or hepatic dysfunction.
  • Apixaban (Eliquis): Another oral factor Xa inhibitor. Studied at 2.5 mg BID for VTE prevention in orthopedic patients (ADVANCE trials). Studied at 5 mg BID for stroke prevention in afib (ARISTOTLE trial). It is not yet approved in the U.S for any indication, but a final decision is expected from the FDA by March. Overall, the data are fairly compelling, and it looks like a strong candidate. The data show a drug that is potentially more effective than lovenox, with less risk of bleeding for orthopedic patients. It is mainly hepatically metabolized.

So, with no drug company relationships to disclose, here are my general observations: For starters, I think dabigatran is being overused in older patients with renal dysfunction. I seem to stop it more than I recommend it, and it is far from my favorite drug. With rivaroxaban, it looks appropriate for VTE prevention, and now having the option of being able to transition patients who develop a clot onto a treatment dose of the drug is appealing. Apixaban’s data look the best out of all three agents in terms of both efficacy and bleeding, and although it is yet to be approved here, I imagine that will change in the near future. For all of these drugs, remember that we have no long-term safety data, and no reversal agents. It will be interesting to see how this plays out and which of these drugs have staying power. For all of warfarin’s faults, at least we know how to measure it and how to stop it.

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