Key result
Switching from acenocoumarol to phenprocoumon initially decreased time in therapeutic range by 5.5 percentage points over the first 180 days, but eventually improved TTR and decreased INR variability in the subsequent 180 days.
Why the study?
Optimal VKA safety and efficacy require high TTR and low INR variability, and switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control.
Does switching from acenocoumarol to phenprocoumon improve time in therapeutic range and INR variability in patients on vitamin K antagonist therapy?
Cohort (n=1,473)
Yes
Does switching from acenocoumarol to phenprocoumon improve time in therapeutic range and INR variability in patients on vitamin K antagonist therapy?
Mean Difference: -5.5 (95% CI -9.6–-1.3)
p-value: p=0.01
Switching from acenocoumarol to phenprocoumon ultimately improves TTR and INR stability, but is preceded by a 6-month transition period of worsened anticoagulation control.
Transient TTR drop warrants transition caution; leaves open long-term phenprocoumon benefit pending prospective confirmation.
BACKGROUND: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. AIMS: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. METHODS AND RESULTS: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'. CONCLUSION: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.
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Miert et al. (2020) conducted a cohort in Atrial fibrillation, venous thromboembolism, or mechanical heart valve replacement requiring vitamin K antagonist therapy (n=1,473). Switching from acenocoumarol to phenprocoumon vs. Continuing acenocoumarol was evaluated on Difference in time in therapeutic range (TTR) over the first 180 days (target range 2.0-3.0) (MD -5.5 percentage points, 95% CI -9.6 to -1.3, p=0.01). Switching from acenocoumarol to phenprocoumon initially decreased time in therapeutic range by 5.5 percentage points over the first 180 days, but eventually improved TTR and decreased INR variability in the subsequent 180 days.
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