Research Article| Volume 398, P69-74, March 15, 2019

Maintenance dose of warfarin beyond time in therapeutic range for preventing vascular events

Published:January 18, 2019DOI:


      • The effectiveness of warfarin is dependent on the quality of anticoagulation control within the INR range of 2.0-3.0.
      • Despite the influence of genetic polymorphisms, the current guidelines do not consider these in all warfarin users.
      • We evaluated a total of 14,831 patients with warfarin medications.
      • In moderate/well-controlled TTR, a lower maintenance dose of warfarin (MDW) was significantly related to vascular events.
      • We propose that patients with a very low MDW might be alternatively considered for NOACs rather than warfarin.



      The quality of anticoagulation is closely associated with efficacy and safety in warfarin users. Although genetic polymorphisms have been related to warfarin dosages and vascular events(VE), genetic evaluations have not been recommended for all warfarin users. The aim is to evaluate the significance of the maintenance dose of warfarin (MDW) on VE, considering the time in therapeutic range (TTR).


      This retrospective study analyzed the data of patients who received warfarin for any reasons. A total of 11,835 patients with warfarin were divided into quartiles by MDW. We assessed TTR using the Rosendaal method and VE.


      VE occurred in 9.1% of the warfarin users. The mean TTR level was 34.0 ± 25.7%, and the MDW was 3.38 ± 1.06 mg per day. Patients with VE were more likely to have a lower MDW and lower TTR levels. In moderate- or well-controlled TTR status, a lower MDW was significantly related to under-controlled anticoagulation and associated with higher risks of VE. Lower MDW had a higher risk of stroke or arterial/venous thromboembolism (Q1: OR, 1.57; 95% CI 1.25 to 1.96; Q2: OR, 1.40; 95% CI 1.12 to 1.75; Q3: OR, 1.35; 95% CI 1.08 to 1.68).


      We suggest that patients with very low MDW might be at risk when using warfarin. Therefore, we propose that patients with a very low MDW might be alternatively considered for novel oral anticoagulants rather than warfarin.


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