Nonrecommended doses of DOACs may increase mortality in patients with AF

  • Camm AJ & al.
  • J Am Coll Cardiol
  • 22 Sep 2020

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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  • In a practice-based registry of patients with recently detected atrial fibrillation (AF), the use of nonrecommended doses of direct oral anticoagulants (DOACs) was not uncommon and was associated with increased risk of all-cause death, mostly cardiovascular death compared with recommended doses.
  • However, nonrecommended doses were not associated with a significant increased risk of stroke/systemic embolism (SE) and major bleeding.

Why this matters

  • Findings highlight the importance of prescribing anticoagulant at the correct recommended dose in order to achieve the most effective results.

Study design

  • This analysis included 10,426 patients with AF who received DOACs (rivaroxaban, 4491 [43.1%]; apixaban, 3290 [31.6%]; dabigatran, 2359 [22.6%]; and edoxaban, 286 [2.7%]) from the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) registry.
  • Funding: supported by an unrestricted research grant from Bayer AG (Berlin, Germany) to the Thrombosis Research Institute, which sponsors the GARFIELD-AF registry.

Key results

  • 7603 (72.9%) patients received recommended dosing, 2423 (23.2%) were underdosed and 400 (3.8%) were overdosed.
  • The risk of all-cause mortality was higher with nonrecommended dosing vs recommended dosing (adjusted HR [aHR], 1.24; 95% CI, 1.04-1.48).
    • nonrecommended underdosing (aHR, 1.25; 95% CI, 1.04-1.50);
    • nonrecommended overdosing (aHR, 1.19; 95% CI, 0.83-1.71).
  • The excess deaths were driven by cardiovascular events including heart failure and myocardial infarction
  • The risks of stroke/SE and major bleeding were not significantly different irrespective of the level of dosing, although the risk of bleeding was significantly lower with nonrecommended low dosing (aHR, 0.50; 95% CI, 0.28-0.88).
  • Nonrecommended high dosing was associated with a nonsignificant trend to higher risks of stroke/SE (HR, 1.51; 95% CI, 0.79-2.91) and major bleeding (HR, 1.29; 95% CI, 0.59-2.78).


  • Uncertainty over renal function may have led to unintended overdosing.
  • Treatment discontinuations or changes in dosage over time were not considered.