60 Feasibility of an Immediate Rapid Reversal of Warfarin Protocol Using a Modified Dosing of a Four-factor Prothrombin Complex Concentrate

Abstract

mortality, it is important to quantify the impact of therapy on developing this adverse event. The number needed to treat (NNT) is a useful measure that can illustrate the effectiveness of an intervention for physician decisionmaking. The objective of this analysis is to quantify the NNT to avoid one event of volume overload in patients receiving 4F-PCC versus plasma for reversal of vitamin K antagonists. Methods: The NNT was determined by calculating the inverse of the absolute risk reduction of volume overload due to 4F-PCC versus plasma using data collected from two open-label, multicenter, phase IIIb clinical trials. In both trials patients were randomly assigned (1:1) to receive either 4F-PCC or plasma. In total, 388 patients (4F-PCC, n¼191; plasma, n¼197) were enrolled. Volume overload occurred in 9 (5%) patients treated with 4F-PCC compared to 25 (13%) patients treated with plasma. In the clinical trials, volume overload events included fluid overload, pulmonary edema, congestive cardiac failure, chronic cardiac failure, and cardiac failure. In addition, the benefit per 100 treated patients was calculated by finding the difference in volume overload events that occurred between one scenario in which 100 patients were treated with 4F-PCC and another scenario in which 100 patients were treated with plasma. Results: The NNT with 4F-PCC, instead of plasma, to avoid one episode of volume overload ranges between 0 and 33.6 among various patient populations (Table 1). These results quantify the extent to which 4F-PCC reduces the likelihood of volume overload. Overall, the average pooled NNT is approximately 12.5. Conclusion: Our pooled analysis suggests that approximately 13 patients need to receive 4F-PCC rather than plasma to avoid one episode of clinically relevant volume overload. For perspective, the NNT with warfarin instead of aspirin to prevent one ischemic stroke is 60 patients. These data may help providers weigh the risks versus benefits of varied treatment options for patients requiring emergency anticoagulation reversal.