Stephan Moll, MD writes… The FDA approved today (Dec 13th, 2013) the use of the drug Kcentra® for urgent warfarin reversal in patients who need an urgent surgical procedure. This extends the indications for use of this drug – it had been approved by the FDA in April 2013 to treat major bleeding on warfarin [ref 1].
The drug is derived from pooled plasma from healthy blood donors and contains the coagulation factors that are low in warfarin-treated patients, i.e. factors II, VII, IX, and X. It is also referred to as a 4-factor concentrate, or non-activated Prothrombin Complex Concentrate (PCC). The study that lead to approval today for the additional indication was presented as an abstract at the American Society of Hematology meeting last week [ref 2]. It has not been published yet in the peer-reviewed literature.
The Study that Lead to Today’s Approval [ref 2]
Methods: Patients requiring rapid reversal of warfarin and other vitamin K antagonists prior to an urgent surgical or invasive procedure were randomized to receive a single dose of either Kcentra® or plasma (fresh frozen plasma, FFP). All patients were to receive vitamin K as early as possible. The primary endpoints were (a) effective peri-operative hemostasis and (b) rapid INR reduction (≤1.3 at 0.5 h after end of infusion).
Results: 168 patients were included (Kcentra® n=87; FFP n=81). Effective hemostasis was achieved in 89.7% of patients in the Kcentra® group versus 75.3% in the FFP group, demonstrating superiority of Kcentra® over plasma (difference 14.3% [95%CI 2.8;25.8]). Rapid INR reduction was achieved in 55.2% of patients in the Kcentra® group versus 9.9% in the FFP group, demonstrating superiority of Kcentra® over FFP(difference 45.3% [95%CI 31.9;56.4]). Side effects were similar between treatment groups. Significantly fewer fluid overload events occurred with Kcentra® than with FFP.
Conclusions: Kcentra was superior to FFP for hemostatic efficacy and for rapid INR reduction, with a favorable safety profile.
- When urgent reversal of warfarin anticoagulation prior to urgent surgery is needed, vitamin K together with 4 factor PCC (Kcentra®) are indicated.
- Vitamin K together with 4 factor PCC (Kcentra®) are also indicated in the case of major bleeding on warfarin.
- However, as recently published in the ASH Choosing Wisely®) campaign and discussed on Clot Connect (link here), FFP and PCC should not be routinely given to patients on warfarin who have elevated INRs but are not bleeding.
- Sarode R et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding. A randomized, plasma-controlled, phase IIIb study. Circulation 2013;128:1234-1243.
- Refaai MA et al. Randomized Phase IIIb Study Of Rapid Vitamin K Antagonist Reversal In Patients Requiring An Urgent Surgical Procedure: Four-Factor Prothrombin Complex Concentrate Is Superior To Plasma. ASH annual meeting, Dec 6-10, 2013 (abstract #3588).
Disclosure: I have been a consultant for CSL Behring, the company making Kcentra®.
Last updated: Dec 13th, 2013