5 New Oral Anticoagulants for Atrial Fibrillation

OCTOBER 24, 2016
When trying to decide which therapy for nonvalvular atrial fibrillation (NVAF) is optimal for patients, many factors should be considered, including compliance, ability to perform daily activities of living, and nutrition replacement. It’s important to initiate the appropriate treatment from the beginning. In all patients with atrial fibrillation (AF), the risk of stroke increases by 500%.1 AF causes blood to circulate slower than normal due to irregular beating of the heart. Decrease in circulation allows blood to accumulate and form clots, which can cause ischemic strokes. Common causes of AF include hypertension, thyroid disease, diabetes, and coronary artery disease.1 Throughout the years, new treatment options have become available for NVAF. Warfarin, a vitamin K antagonist (VKA), has been the cornerstone treatment of NVAF, but certain monitoring parameters and restrictions make it difficult for certain patient populations to maintain compliance. New oral anticoagulants (NOAC) for NVAF include apixaban, dabigatran, rivaroxaban, and edoxaban.2 These new oral anticoagulants have quicker onset of action and shorter half-lives, and some proceed through renal elimination.

Warfarin
Warfarin interferes with the action of vitamin K, which is involved in blood clotting processes. A downside for patients is that this medication requires a lot of monitoring due to narrow therapeutic index. It requires frequent international normalized ratio (INR) monitoring at clinics. This may require patients to drive to these clinics on numerous days throughout the week for the drugs to become therapeutic. Food interactions and patient genetic profile may affect overall efficacy of warfarin. It’s important to keep a consistent amount of vitamin K in the daily diet to help maintain a therapeutic INR of 2-3.1 Efficacy of warfarin has been proven in clinical trials. A systematic review of clinical trials found that in patients with AF, warfarin can provide reduction in stroke and death rate.1 Vitamin K can be used to reverse the effects of warfarin in emergent situations of excess bleeding. 

Dabigatran
This factor II inhibitor works in the coagulation pathway to help prevent formation of blood clots. It can be used to treat NVAF and is dosed twice daily, which could potentially effect compliance for certain patients. The bioavailability of dabigatran is 7%, the lowest of all NOAC.2 When taken with food, the time to peak is increased compared to consumption without food.3 Dabigatran doesn’t require routine monitoring, so it may be an appropriate option for patients who aren’t able to get routine monitoring. The reversal agent of dabigatran is idarucizumab. Currently, none of the other NOAC have available reversal agents in the United States.

Apixaban
This factor Xa inhibitor works in the coagulation pathway to prevent formation of blood clots. It’s dosed twice daily for NVAF, but the dosage should be lowered if the patient categorized under at least 2 of the following: serum creatinine is greater than 1.5 mg/dL, age is 80 years or older, or weight less than 60kg.2 Routine monitoring isn’t required with this medication. One study’s results showed a lower rate of ischemic stroke occurrence with the use of apixaban compared to warfarin.4 An antidote for factor Xa inhibitors is currently being tested. Andexanet alfa is in clinical trials with patients using apixaban, rivaroxaban, edoxaban, or enoxaparin who present with major bleeding.5
 
Rivaroxaban
This factor Xa also works in the coagulation pathway to prevent formation of blood clots. It’s dosed once daily for NVAF, which is believed to improve patient compliance. This may be an appropriate option for patients with a history of noncompliance with previous medications. The dosage for NVAF is 20 mg once daily with food, which is important for increased absorption.6 Study results have shown rivaroxaban to be noninferior to warfarin in patients with AF. In a recent observational study published in JAMA Internal Medicine, it was found that rivaroxaban treatment for NVAF was associated with an increase in intracranial hemorrhage, extracranial bleeding, and gastrointestinal bleeding.7

Edoxaban
This is another factor Xa inhibitor with the same mechanism of action as the other factor Xa inhibitors mentioned in this article. It’s dosed once daily for NVAF, another option for noncompliant patients. Use isn’t recommended for any patient with a creatinine clearance greater than 95 ml/min.8 One study results showed that high-dose edoxaban (60 mg) wasn’t statistically significant for lower incidence of ischemic stroke compared to warfarin.9 The rate of hemorrhagic stroke was reduced in both high and low dose (30 mg) regimens compared to warfarin.
 
References
1. Atrial Fibrillation Association. Chapter 1 – what is AF? AFA website. preventaf-strokecrisis.org/report/chapter1/.
2. Urooj F, et al. New oral anticoagulants in nonvalvular atrial fibrillation. Clin Cardiol. 2016.
3. Pradaxa- dabigatran etexilate. Dailymed. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ba74e3cd-b06f-4145-b284-5fd6b84ff3c9&audience=consumer.
4. Granger CB, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992. nejm.org/doi/full/10.1056/NEJMoa1107039#t=article.
5. Clinical Development. Andexanet alfa: FXa inhibitor antidote. Portola Pharmaceuticals website. www.portola.com/clinical-development/andexanet-alfa-fxa-inhibitor-antidote/.
6. Xarelto- rivaroxaban tablet. Dailymed. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=10db92f9-2300-4a80-836b-673e1ae91610&audience=consumer.
7. Graham DJ, et al. Stroke, bleeding, and mortality risks in elderly medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Internal Med. 2016.
8. American Pharmacist Association. Edoxaban: Fourth novel oral anticoagulant approved. APhA website. pharmacist.com/edoxaban-fourth-novel-oral-anticoagulant-approved.
9. Bounameaux H, et al. Edoxaban: an update on the new oral direct factor Xa inhibitor. Drugs. 2014;74(11):1209-1231.

Shivam Patel, Pharm.D.
Shivam Patel, Pharm.D.
Dr. Shivam Patel has graduated from Lake Erie College of Osteopathic Medicine (LECOM) School of Pharmacy with a Doctor of Pharmacy degree. He is a PGY1 Pharmacy Resident at Martinsburg VA Medical Center. His professional interests include critical care, infectious disease, and ambulatory care. After completion of his PGY1 residency, Dr. Patel hopes to continue to serve veterans and become a Clinical Pharmacy Specialist.
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