Personalizing anticoagulant treatments for nonvalvular atrial fibrillation

Colored angiogram of the brain of a 48-year-old patient after a massive stroke.
Colored angiogram of the brain of a 48-year-old patient after a massive stroke.

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The American Heart Association estimates that atrial fibrillation (AF) affects approximately 2.7 million Americans.1 It is projected that cases of AF will increase to 12.1 million by the year 2030; however, there is much uncertainty within the magnitude of future trends in capturing diagnosis and morbidity of the sequela associated with AF.2 In addition to being the most common cardiac arrhythmia, AF is also classified as the most common rhythm disorder among adults aged older than 65 years living in the United States.

Determining treatment for any individual with nonvalvular AF requires a balance between the risks and benefits of oral anticoagulation therapy. Individualized selection of an anticoagulant is based on stroke and bleeding risk, cost, interactions, likelihood of adherence to medication regimen, and individual patient preference related to lifestyle. Anticoagulation therapy for individuals who require more than aspirin therapy may include one of the three inhibitors of activated factor X (factor Xa), rivaroxaban, apixaban, or edoxaban; a direct thrombin inhibitor, dabigatran; or a vitamin-K-dependent inhibitor, warfarin.3,4

Direct factor Xa inhibitors

Direct factor Xa inhibitors cause selective inhibition of factor Xa, which aids in the formation of thrombin, abetting the development of thrombosis.5 There are three oral direct factor Xa inhibitors approved by the US Food and Drug Administration (FDA) for the treatment of nonvalvular AF: rivaroxaban, apixaban, and edoxaban.

Rivaroxaban. The recommended dosing of rivaroxaban is 20 mg daily taken with an evening meal if creatinine clearance (CrCl) is greater than 50 mL/min (Table 1).6 For patients with a CrCl between 15 and 50 mL/min, 15 mg daily taken with an evening meal is recommended.6 Rivaroxaban is not recommended for individuals with a CrCl less than 15 mL/min due to the decreased clearance of the drug through the kidneys.6 The drug should be withdrawn if the patient develops acute renal failure.6

Rivaroxaban's plasma concentration is as high as 80% to 90%, with peak plasma levels 2 to 4 hours after dosing.6 It is primarily eliminated in the urine, approximately 36% unchanged.6 The half-life of rivaroxaban is approximately 5 to 9 hours.6 In individuals with renal impairment, clearance of the drug may differ.

Patients with moderate to severe hepatic impairment, particularly those with coagulopathy concerns, should avoid rivaroxaban.6 Common reactions and side effects include bleeding, pruritus, and elevation of liver enzymes.5

Click to enlarge.

Apixaban. The recommended dosing of apixaban is 5 mg twice daily (Table 1).7 In patients with at least two of the following characteristics, the recommended dose is 2.5 mg twice daily: age 80 years or older; body weight less than 60 kg; or serum creatinine level of 1.5 mg/dL or greater.7

Plasma protein binding of apixaban is approximately 87%; the drug has a half-life of 12 hours, and a peak effect is reached within 3 to 4 hours.7 Common side effects of apixaban include bleeding, anemia, nausea, skin rash, or a more serious allergic reaction.7

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