To date, several pharmaceutical companies started marketing an entirely new line of blood thinning medications (popularly called Novel Oral Anticoagulants or NOACs) that have been advertised as a much simpler and convenient alternative for people at risk for stroke. Strokes are caused by blood clots that lodge in a blood vessel in the brain, cutting off the oxygen supply. The consequences could be dire, and include permanent injuries and, in some instances, may cause the death of the patient.
In the last 50 years, the standard in treatment for the prevention of blood clots was warfarin: a substance also used as rat poison. It is synthesized from a substance known as coumarin, a pleasantly-scented chemical found in sweet clovers and woodruff.
In 1954, the Food and Drug Administration (FDA) approved warfarin to reduce the risk of stroke caused by blood clots. The newly discovered anticoagulant was then also approved to treat over 2 million U.S citizens suffering from atrial fibrillation (afib). Commercially marketed as Coumadin, Warfarin dominated the entire anticoagulants scenario for years to come before new drugs have been introduced.
Warfarin’s main drawback was its constant need for monitoring, as a patient’s life may be at risk if its blood levels are either too high or too low. Many food types such as kale, leafy greens or spinach, in fact, are rich in a substance called Vitamin K which may antagonize its effects. However, for this same reason, if its dose is too high, a patient can be saved from harm and potentially lethal bleeding by injecting him or her a dose of Vitamin K.
When drugs as Xarelto (the NOACs) hit the market, their principal advantage was the absence of important reactions with food or other drugs. Patients did not require any controls nor dietary restrictions, but convenience came at a very high price (other than its expensively market price). Factor Xa inhibitors lacked any effective method to reverse their effects, since no antidote was available. Whenever a bleeding accident occurs, not even emergency dialysis may save the patient’s life, and even a small domestic accident or a minor trauma can have mortal consequences.
The differences between Warfarin and Xarelto
- Patients taking warfarin need to pay a lot of attention to what they eat. Their blood nee get blood be tested at least once every month, and they must be careful about how much Vitamin K they consume. Many foods like chard or kale must be avoided and this can be an issue to a lot of people. Xarelto has no dietary restrictions to cope with instead.
- Warfarin is linked with a risk for brain bleedings which may be lethal, even if they’re quite uncommon. Xarelto’s bleeding are less frequent, but when they happen, they cannot be stopped. The newer drug half-life is short though, so in less than a day it’s out of a patient’s body.
- Xarelto has just a single dosage: 20 mg to reduce the risk of stroke. It’s taken once per day with meals, usually in the evening. Warfarin dosage varies wildly. It depends on factors such as weight, age, diet, and concomitant drugs therapy. If the dose is too high, there’s a risk of bleeding. If it’s too low, blood clots may occur.
- Xarelto’s mechanism of action depends on the levels of Vitamin K in the blood. The dosage must be continuously titrated to optimize its effectiveness. The more Vitamin K available (it’s naturally produced by the body), the lesser is the time blood takes to clot, so higher doses of Warfarin are needed. works otherwise. Xarelto’s dosage is independent of Vitamin K levels instead, and no monitoring is required at all.
- Xarelto’s cost is much higher than Warfarin’s especially to people who have no insurance plan. However, for those who have one the difference in price is negligible.
Article written by Dr. Claudio Butticè, Pharm.D.
. Xarelto Full prescribing information – (rivaroxaban) tablets, for oral use. Retrieved from: http://www.xareltohcp.com/shared/product/xarelto/prescribing-information.pdf
. “Bleeding with dabigatran, rivaroxaban, apixaban. No antidote, and little clinical experience.” Prescrire Int. 2013 Jun;22(139):155-9.
. Jaeger M, Jeanneret B, Schaeren S. “Spontaneous spinal epidural haematoma during Factor Xa inhibitor treatment (Rivaroxaban).” Eur Spine J. 2012 Jun;21 Suppl 4:S433-5.
. Daniel S. Budnitz, M.D., M.P.H., Maribeth C. Lovegrove, M.P.H., Nadine Shehab, Pharm.D., M.P.H., and Chesley L. Richards, M.D., M.P.H. Emergency Hospitalizations for Adverse Drug Events in Older Americans. N Engl J Med 2011; 365:2002-2012
. Raunsø J, Selmer C, Olesen JB, Charlot MG, Olsen AM, Bretler DM, Nielsen JD, Dominguez H, Gadsbøll N, Køber L, Gislason GH, Torp-Pedersen C, Hansen ML. Increased short-term risk of thrombo-embolism or death after interruption of warfarin treatment in patients with atrial fibrillation. Eur Heart J. 2012 Aug;33(15):1886-92.
. Patel MR, Mahaffey KW, Garg J, et al; and the ROCKET AF Steering Committee, for the ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891.
. Bruce L. Davidson, Sara Verheijen, Anthonie W. A. Lensing, Martin Gebel, Timothy A. Brighton, Roger M. Lyons, Jeffrey Rehm, Martin H. Prins: “Bleeding Risk of Patients With Acute Venous Thromboembolism Taking Nonsteroidal Anti-Inflammatory Drugs or Aspirin.” JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946.
. J P Hanley “Warfarin reversal” J Clin Pathol. 2004 Nov; 57(11): 1132–1139.
. Food and Drug Administration Web site. “Adverse Event Reporting System (AERS). (2011)” http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm (Accessed February 2011).