Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial.
The use of vitamin K antagonists, such as warfarin, has been increasing over the last decades and despite the surge of the novel oral anticoagulants, warfarin is the most widely used anticoagulant worldwide. When immediate reversal of the anticoagulant effect of vitamin K antagonists is needed, for example in patients who present with major haemorrhage or require urgent surgical or otherwise invasive interventions, levels of vitamin K-dependent factors can be restored by administration of plasma or prothrombin complex concentrate (PCC). In some countries, including the US, PCC is not universally available, and patients have to be treated with plasma. The disadvantage of plasma for this indication is the relatively large volume that is required to correct haemostasis, potentially leading to long infusion times resulting in delayed administration and fluid overload.
This randomised controlled trial compared the administration of INR-dependent dosing of either PCC or plasma in 168 patients requiring rapid reversal because of the need for an invasive intervention. The primary outcome, haemostasis during surgical or invasive interventions, was observed in 90% of patients in the PCC group compared with 75% in the plasma group (difference between groups 14.3%, 95% confidence interval 2.8-25.8). The reduction of INR was significantly faster in the PCC group compared with the plasma group. Thromboembolic complications occurred in 7% of patients receiving PCC and in 8% of patients receiving plasma.
This is an important and relevant study. PCC for reversal of vitamin K antagonists is common clinical practice in many parts of the world but firm evidence for this treatment was lacking. The licensing of PCC in countries where it is not yet available allows the conduct of studies filling this gap. This study clearly shows the efficacy and relative safety of PCC for warfarin reversal, which is important in emergency situations. The information on PCCs is also helpful because this intervention is used for the reversal of the anticoagulant effect of novel direct oral anticoagulants such as rivaroxaban, apixaban and dabigatran.
– Marcel Levi