Comparing Warfarin to NOACs

Warfarin was initially approved by the Food and Drug Administration (FDA) for use in humans to prevent blood clots in 1955.1 For more than half a century, warfarin has been the only pill option for patients who needed to take an anticoagulant, or ‘blood thinner.’ However warfarin is not without issues, including requiring frequent blood test monitoring due to possible food and drug interactions. Since 2010, several new drugs have been approved for use in treating and preventing blood clots. The first drug was approved in October, 2010, and is called dabigatran (Pradaxa®).

In the years that followed, three additional drugs were approved: rivaroxaban (Xarelto®), apixaban (Eliquis®), and edoxaban (Savaysa®).3 The new drugs, sometimes called NOACs (Novel Oral Anticoagulants) or DOACs (Direct Oral Anticoagulants) target very specific factors in the very complex clotting process.2

Is there clinical equivalence between warfarin and other anticoagulants?

To be approved by the FDA, all new medications must undergo rigorous clinical trials. During the trials for the NOACs, their use for the prevention of stroke caused by a blood clot was investigated. What the trials discovered is that the new oral anticoagulants had similar effectiveness, not better, when compared to warfarin. It should be noted that the trials compared the new drugs to warfarin with a time in-range of less than 65%. This means the International Normalized Ratio (INR), the blood test to check effectiveness of warfarin, was in the patient’s target range (for atrial fibrillation, this is usually between 2.0 and 3.0) less than 65% of the time. The trials also found that warfarin is very effective and reduces stroke from blood clots by two-thirds, when compared with no treatment at all. The trials did find an increase in bleeding in the intestinal tract on the NOACs as compared to warfarin. Otherwise, these new agents had a favorable safety profile. 2 Essentially, the NOAC drugs were found to be ‘clinically equivalent’ to warfarin.4

If these new drugs had been studied against well-controlled warfarin (time in-range greater than 70%), how would the outcomes differed? In the STABLE study, patients on warfarin tested their INR at home using a finger-stick drop of blood and a device for home use. The study found that the average time in-range for the entire group was 69.7%. Those patients who tested their INR at home once per week were able to achieve a time in-range of 74%. Another significant finding in this study is that weekly testers also experienced fewer critical values (values when the INR was less than 1.5 or greater than 5.0).5

If you are on warfarin and your INR is not well controlled (time in-range less than 65%), your doctor may consider home INR testing as a way to improve your time in-range, before considering a switch to a new drug. If you are on warfarin and your INR is well controlled (time in-range greater than 65%), there is no clinical benefit in switching to a NOAC. You should speak with your doctor if your have any questions about your INR results and your time in-range.

The idea that novel anticoagulants are better than warfarin for patients with atrial fibrillation is a complex one and should be discussed on an individual basis with your physician, weighing the pros and cons of all options.

References:

  1. Finkel, R. Coming Upon Coumadin: How Warfarin was Discovered. Drug Information and Side Effects Database (Drugsdb.com). Aug 2, 2012. Retrieved from the website: http://www.drugsdb.com/blog/coming-upon-coumadin-how-warfarin-was-discovered.html.
  2. Hanley, C.M. et al. Are the novel anticoagulants better than warfarin for patients with atrial fibrillation? J Thorac Dis. 2015 Feb; 7(2): 165-171.Retrieved from the website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321074/.
  3. Drugs.com Pradaxa Approval History. 2017. Retrieved from the website: https://www.drugs.com/history/pradaxa.html.
  4. Mandrola, J. Novel Oral Anticoagulants vs Warfarin: The Truth is Relative. Medscape. Dec 18, 2013. Retrieved from the website: http://www.medscape.com/viewarticle/818013.  
  5. DeSantis, G., PhD. et al. STABLE Results: Warfarin Home Monitoring Achieves Excellent INR Control. American Journal of Managed Care. March 2014.

Pradaxa® is a registered trademark of Boehringer Ingelheim Pharmaceuticals, Inc.. Xarelto® is a registered trademark of Janssen Pharmaceuticals, Inc. Eliquis® is a registered trademark of Bristol-Myers Squibb Company. Savaysa® is a registered trademark of Daiichi Sankyo, Inc.  Alere is not affiliated or associated with the noted trademark owners or their related trademarks.