Direct Oral Anticoagulants or Warfarin for A-fib?

A 66-year-old man with a history of hypertension and type 2 diabetes is hospitalized for palpitations and dizziness and is diagnosed with atrial fibrillation (A-fib). His heart rate is successfully regulated with a ß-blocker. He has a CHA₂DS₂-VASc score of 3, making him a candidate for anticoagulation. Which agent should you start?

Thromboembolism in patients with A-fib often results in stroke and death, but appropriate use of antithrombotic therapy can reduce risk. Evidence-based guidelines recommend that patients with A-fib at intermediate or high risk for stroke (CHADS₂ score ≥ 2, or prior history of cardioembolic stroke or transient ischemic attack) receive antithrombotic therapy with oral anticoagulation, rather than receive no therapy or therapy with antiplatelets.^2,3

The American College of Chest Physicians also recommends use of the direct oral anticoagulant (DOAC) dabigatran instead of warfarin for those patients with nonvalvular A-fib with an estimated glomerular filtration rate ≥ 15 mL/min/1.73 m².³

A meta-analysis of large randomized controlled trials (RCTs) investigated individual DOACs: dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. The results revealed similar or lower rates of ischemic stroke and major bleeding (except gastrointestinal bleeds; relative risk, 1.25) when compared with warfarin (at an international normalized ratio [INR] goal of 2-3).⁴ In addition, three separate meta-analyses that pooled results from large RCTs involving dabigatran, apixaban, and rivaroxaban also concluded that these medications significantly reduced incidence of embolic stroke and risk for major bleeds and hemorrhagic stroke, compared with warfarin.^5-7

However, less is known about the comparative effectiveness and safety of the ­DOACs when they are used in clinical practice, and it is not clear which, if any, of these agents is superior to others. Moreover, only about half of the patients in the United States with A-fib who are eligible to take DOACs are currently managed with them.⁸

STUDY SUMMARY

Different DOACs, different benefits

This large cohort study used data from three Danish national databases to assess the effectiveness of three DOACs compared with warfarin. The nearly 62,000 patients had been recently diagnosed with A-fib without valvular disease or venous thromboembolism. Subjects were prescribed either standard doses of dabigatran (150 bid; N = 12,701), rivaroxaban (20 mg/d; N = 7,192), or apixaban (5 mg bid; N = 6,349) or dose-adjusted warfarin to an INR goal of 2 to 3 (N = 35,436). Patients were followed for an average of 1.9 years.

Ischemic stroke, systemic emboli. In the first year of observation, there were 1,702 reports of ischemic stroke or systemic emboli. The incidence of ischemic stroke or systemic embolism was the same or better for each of the three DOAC treatments than for warfarin (2.9-3.9 vs 3.3 events per 100 person-years, respectively). Ischemic stroke or systemic emboli events occurred less frequently in the rivaroxaban group than in the warfarin group at one year (hazard ratio [HR], 0.83) and after 2.5 years (HR, 0.80). The rates of ischemic stroke and systemic emboli for both apixaban and dabigatran were not significantly different than that for warfarin at either end-point.

Bleeding events (defined as intracranial, major gastrointestinal, and traumatic intracranial) were lower in the apixaban group (HR, 0.63) and dabigatran group (HR, 0.61) than in the warfarin group at one year. Significant reductions remained after 2.5 years. There was no difference in bleeding events between rivaroxaban and warfarin.

Risk for death. Compared with warfarin, the risk for death after one year of treatment was lower in the apixaban (HR, 0.65) and dabigatran (HR, 0.63) groups, and there was no significant difference in the rivaroxaban group (HR, 0.92).