OBJECTIVES: The objective of this systematic review and meta-analysis is to evaluate the efficacy, safety, time to INR reversal, total volume of 4-factor prothrombin complex concentrate (PCC) administered of fixed-dose versus weight-based dosing strategies in patients requiring urgent warfarin reversal, with specific focus on clinical outcomes such as hemostatic efficacy, thromboembolic events, and mortality rates.

METHODS: A comprehensive systematic review was conducted using the PubMed, Embase, and Cochrane databases from inception through October 2023. We searched for randomized clinical trials or observational studies that compared efficacy or safety outcomes of fixed-dose vs. variable 4-PCC dose in adult patients.

RESULTS: A total of fourteen studies were included. The overall use of fixed-dose 4-PCC was associated with a lower likelihood of reaching the INR goal (RR = 0.84, 95% CI 0.80 - 0.89) and a significantly higher proportion of patients (169 out of 651 [26%]) required an additional dose of 4-PCC compared to the variable-dose group. The rate of mortality (RR = 0.85, 95% CI 0.70 - 1.03) and thromboembolic events (RR = 1.27, 95% CI 0.65 - 2.45) were similar between the two treatment groups.

CONCLUSIONS: This systematic review and meta-analysis showed that variable dosing of 4-PCC more successfully achieves the target INR for warfarin reversal compared to fixed dosing. However, both dosing strategies have similar mortality and thromboembolic rates. While fixed dosing offers a simpler approach, it may require additional dosing. Future studies should focus on optimizing dosing strategies to balance efficacy, safety, and practicality in various clinical scenarios.