Direct-Acting Oral Anticoagulants

Over the past decade, the market has seen the addition of several new oral anticoagulants that act by directly inhibiting thrombin or activated factor X (Factor Xa) (Table 2). These DOACs can be given at fixed doses without the need for routine coagulation monitoring, which simplifies treatment. Meta-analyses have found that DOACs are as or even more effective than warfarin in reducing the risk of thromboembolic events.10-12 DOACs are also associated with lower rates of intracranial hemorrhage compared with warfarin.10,11 However, most DOACs increase the risk of gastrointestinal bleeding.10-12

Dabigatran is a direct thrombin inhibitor. It is available in dose strengths of 75 mg, 110 mg, and 150 mg administered twice daily. For stroke prevention in NVAF, dabigatran should be administered at 150 mg twice daily, and the dosage should be reduced to 75 mg twice daily for patients with a CrCl of 15 to 30 mL/min.13 In clinical trials, dabigatran 150 mg twice daily was found to be superior to warfarin, and dabigatran 110 mg twice daily was found to be noninferior to warfarin for the primary outcome of stroke (any type) and systemic embolism.13 Both the 110-mg and 150-mg doses significantly lowered the risk of hemorrhagic stroke by 74% and had lower rates of intracranial bleeding and life-threatening bleeding.13 The rate of major bleeding was similar to that seen with warfarin, while the rate of gastrointestinal bleeding was higher at the 150-mg dose.13 The most common adverse events are gastritis-like symptoms and bleeding.13 Dabigatran is primarily excreted by the kidneys; thus, plasma concentrations are increased in patients with moderate renal impairment (CrCl <50 mL/min).14

Apixaban is a direct factor Xa inhibitor. It is available in dose strengths of 2.5 mg and 5 mg administered twice daily. For stroke prevention in NVAF, apixaban should be administered at 5 mg twice daily, and the dosage should be reduced to 2.5 mg twice daily in certain conditions.15 In clinical trials, apixaban was found to be superior to warfarin in the primary outcomes of stroke and systemic embolism as well as in major bleeding.15 Rates of intracranial bleeding were lower in patients treated with apixaban, and rates of gastrointestinal bleeding were similar.15 The most common adverse events are bleeding-related.15 Apixaban is metabolized in the liver via CYP3A4-dependent and CYP3A4-independent mechanisms and should not be used in patients with severe hepatic impairment.14

Edoxaban is a direct factor Xa inhibitor. It is available in dose strengths of 15 mg, 30 mg, and 60 mg administered once daily. For stroke prevention in NVAF, edoxaban should be administered at 60 mg once daily for patients with a CrCl of >50 to £95 mL/min, and the dosage should be reduced to 30 mg once daily for patients with a CrCl of 15 to 50 mL/min.16 In clinical trials, both edoxaban 60 mg once daily and edoxaban 30 mg once daily were found to be noninferior to warfarin with respect to the primary outcome of stroke and systemic embolism.16 Both doses also significantly lowered rates of major bleeding compared with warfarin.16 The most common adverse events are bleeding and anemia.16 Edoxaban is metabolized in the liver via a CYP3A4-dependent pathway and should not be used in patients with moderate or severe hepatic impairment.14

Rivaroxaban is a direct factor Xa inhibitor. It is available in dose strengths of 2.5 mg, 10 mg, 15 mg, and 20 mg administered once daily. It should be consumed with the evening meal to ensure adequate absorption.17 For stroke prevention in NVAF, rivaroxaban should be administered at 20 mg once daily with the evening meal, and the dosage should be reduced to 15 mg once daily for patients with a CrCl of £50 mL/min.17 In clinical trials, rivaroxaban was found to be noninferior to warfarin with respect to the primary outcome of stroke and systemic embolism, and major bleeding was similar.17 Gastrointestinal bleeding was higher with rivaroxaban, but rates of intracranial hemorrhage and fatal bleeding were lower.17 The most common adverse events are bleeding-related.17 Rivaroxaban is metabolized in the liver via CYP3A4-dependent and CYP3A4-independent mechanisms and should not be used in patients with severe hepatic impairment.14