A trial fibrillation (AF), the most prevalent type of arrhythmia, affects an estimated 2.7 to 6.1 million people in the United States.1 Patients with AF are at a 4 to 5 times higher risk of stroke, and AF accounts for 15% to 20% of ischemic strokes in the U.S. Strokes related to AF are more severe than are strokes caused by other underlying disease.2 For many years, warfarin (vitamin K antagonist) has been the mainstay treatment of AF-related stroke. Warfarin is highly effective in reducing the risk of AF-related stroke but has substantial limitations that can outweigh those advantages-including a narrow therapeutic window and certain drug-drug and drug-food interactions.3 To overcome these limitations, recent years have seen the production of new oral anticoagulants (NOACs), such as factor Xa (rivaroxaban, apixaban, and edoxaban) inhibitors and direct thrombin inhibitors (dabigatran). Table I
WarfarinWarfarin, introduced in 1954, is very effective in preventing AF-related strokes. Warfarin is reversible and inexpensive, and anticoagulation with warfarin (international normalized ratio, 2-3; mean, 2.5) has been shown to decrease AF-related stroke risk by 67%. However, warfarin still remains underused by about 50% of suitable candidates receiving treatment for AF. Warfarin therapy has some limitations, such as a slow onset of action, genetic variation in metabolism, multiple food and drug interactions, and a narrow therapeutic index that makes it difficult to use in practice.5 Therefore, there is a need in AF management for novel approaches to stroke prevention with NOACs.
DabigatranDabigatran is a selective and reversible, oral, direct thrombin inhibitor. The absolute bioavailability of dabigatran, after oral administration, is around 6.5% (serum halflife, 12-17 hr), which warrants twice-daily dosing. 6 Renal excretion is the primary route of elimination of dabigatran (80%). The approved doses of dabigatran in the U.S. are 150 mg twice daily in patients with normal renal function and 75 mg twice daily both in patients with poor renal function (creatinine clearance [CrCl], 15-30 mL/min) and in patients with CrCl 30-50 mL/min in the presence of P-glycoprotein inhibitors. Dabigatran is contraindicated in patients with CrCl <15 mL/min or in patients who are taking P-glycoprotein inhibitors with CrCl <30 mL/min.6 Idarucizumab is a humanized monoclonal antibody fragment, derived from an immunoglobulin G-isotype molecule, which reverses the anticoagulant effects of dabigatran.
RivaroxabanRivaroxaban is an oral, direct factor Xa inhibitor with a bioavailability of 70% and a serum half-life of 5 to 9 hours in healthy volunteers and 11 to 13 hours in the elderly. Two thirds of a rivaroxaban dose undergoes metabolic degradation in the liver, of which half is eliminated renally and half is removed via the hepatobiliary route in the feces. 4 The influence of renal function on rivaroxaban is considered to be moderate, and rivaroxaban is prescribed at oral dosages of 20 mg/d with evening meals (if CrCl >50 mL/min) or 15 mg/d...