Melanie Condeni, BCCCP, BCPS, PharmD
Pharmacist
MUSC Health of Medical University of South Carolina
Charleston, SC, United States
Disclosure information not submitted.
Kyle Weant, BCCCP, BCPS, PharmD
Clinical Assistant Professor
University of South Carolina College of Pharmacy, United States
Disclosure information not submitted.
Ron Neyens, PharmD
Clinical Pharmacy Specialist
MUSC Health of Medical University of South Carolina, United States
Disclosure information not submitted.
Evert Eriksson, MD, FACS, FCCM
Professor
MUSC Health of Medical University of South Carolina, United States
Disclosure information not submitted.
Todd Miano, PharmD, PhD
Critical Care Pharmacist
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania, United States
Disclosure information not submitted.
Title: Fixed vs variable-dose prothrombin complex concentrate in warfarin-related bleeding: a meta-analysis
INTRODUCTION/HYPOTHESIS: Though four-factor prothrombin complex concentrate (PCC) is the standard of care for emergent warfarin reversal, the optimal approach to dosing is uncertain. In this systematic review and meta-analysis, we estimated the proportion of patients treated with fixed dose (FD) PCC who achieved adequate reversal, and compared the rate of adequate reversal in patients who received FD vs. weight based (WB) dosing.
Methods: Medline and Scopus were searched from January 2000 to March 2021 for English language controlled trials and observational studies in adults. We included studies that evaluated only FD regimens and those that compared FD and WB dosing regimens for emergent warfarin reversal. Outcomes were achievement of goal international normalized ratio (INR) and survival to hospital discharge. Pooled estimates were obtained using random effects meta-analysis. Effect heterogeneity was examined in subgroup analysis. Risk of bias was assessed using validated tools.
Results: 18 observational studies (n=1759) were included. 11 studies (n=874) included only patients who received a FD regimen, and 7 studies (n=885) compared FD vs. WB regimens. In patients treated with FD, the proportion of patients achieving goal INR varied depending on the INR target, being significantly higher for goal INR< 2 (90.8%, CI95 86.5, 94.5) compared to goal INR< 1.6 (72.0%, CI95 66.7, 77.1). Compared to WB dosing, FD was less likely to achieve a goal INR of < 1.6 (Risk Difference (RD) -16.0%, CI95 -27.0, -6.0) but achieved similar reversal for a goal INR of < 2.0, (RD -2.0%, CI95 -8.0, 5.0). In 4 studies (n=539) there was no difference in hospital mortality (RD 2.0%, CI95 -9.0, 12.0). In 6 studies (n=659) there was no difference in thrombosis (RD -1.0%, CI95 -3, 2.0).
Conclusions: FD-PCC for warfarin reversal was associated with significantly lower attainment of goal INR compared to WB dosing when goal INR was 1.6 or lower, but not when goal INR was < 2. Differences in INR attainment did not lead to differences in hospital mortality, but these results should be interpreted cautiously in light of the observational nature of the included studies. Further research is needed to define the most appropriate dosing of PCC for warfarin reversal.