The phenprocoumon echo: Elevated INR risk after VKA reversal - A retrospective analysis of phenprocoumon and acenocoumarol in clinical practice in a Dutch teaching hospital.

INTRODUCTION: In case of excessively elevated INR values (INR > 6), major bleeding or emergency surgery, there is a need to reverse the anticoagulant effect of vitamin K antagonists (VKAs). Phenprocoumon’s longer half-life poses greater challenges for reversal compared to acenocoumarol when using short-acting agents like phytomenadione and prothrombin complex concentrate (PCC). Data on supratherapeutic INR recurrence after reversal of both acenocoumarol and phenprocoumon remain limited. This study aims to compare the incidence of supratherapeutic INR following reversal with PCC and/or phytomenadione in patients using phenprocoumon versus acenocoumarol. METHODS: A retrospective observational study was conducted at Spaarne Gasthuis (Haarlem/ Hoofddorp, the Netherlands), analysing data from 2009 to 2024. Patients using acenocoumarol or phenprocoumon who achieved successful reversal (INR ≤ 2.0 within 48 h) with PCC and/or phytomenadione were included. Patients were followed from 48 h post-reversal until INR > 3.5, VKA resumption, discharge, death, or 14 days post-reversal. The primary outcome was the time to elevated INR (> 3.5). RESULTS: A total of 2,334 admissions were included. In 1,506 admissions, no INR was measured during follow-up. Phenprocoumon use was associated with a significantly higher risk of supratherapeutic INR after both PCC-based reversal (HR: 4.01, 95% CI: 1.41–15.30) and phytomenadione alone (HR: 3.71, 95% CI: 1.20-14.72). The risk was especially pronounced in patients with a baseline INR ≥ 6. CONCLUSION: Phenprocoumon use is associated with a higher risk of supratherapeutic INR elevation following reversal compared to acenocoumarol use. In patients with a baseline INR ≥ 6, almost all recurrences were in phenprocoumon users.