More precise dosing of acenocoumarol for better control in patients aged above 80 years, a randomised controlled pilot study

Introduction: Many elderly patients are confined to treatment with vitamin K antagonists (VKA) instead of direct oral anticoagulants (DOACs). However, quality of VKA treatment declines with age. This might be caused by the lower dose requirements with increasing age, which result in relatively large day-by-day VKA dose differences. Therefore, more precise dosing with smaller dose increments might improve quality of VKA treatment in the elderly.

Methods: We randomised 80 elderly patients (≥80 years, using 0.5-2 mg acenocoumarol daily) to either conventional dosing with 1.0 mg acenocoumarol increments, or more precise dosing with 0.5 mg increments, to assess effect sizes and feasibility of a larger trial. We compared changes in the time in therapeutic range (TTR), INR variability and anticoagulation-related quality of life (measured with the PACT-Q) between treatment groups.

Results: Overall, baseline TTR was 61.3 ± 19.2. After six study months, TTR had improved to 69.5 ± 19.7 in the precise dosing group versus 67.7 ± 21.2 in the conventional dosing group (absolute difference 3.4 (95% CI -6.7 to 13.6)). The between-groups difference in INR variability was not assessed because of baseline differences. PACT-Q convenience declined slightly with more precise dosing, compared with conventional dosing: 2.1/100 (95% CI 0.5-3.7). Satisfaction decreased equally in both groups with -6.4 ± 8.6/100. Four dosing errors occurred: three with precise and one with conventional dosing.

Conclusion: Although more precise dosing of acenocoumarol leads to a slightly higher TTR, this effect is too small to convey a relevant clinical benefit and could be abolished by the increased risk of medication errors.