Treatment of Factor-Xa Inhibitor-associated Bleeding with Andexanet Alfa or 4 Factor PCC: A Multicenter Feasibility Retrospective Study

Abstract

Background There are no randomized trials comparing andexanet alfa and 4 factor prothrombin complex concentrate (4F-PCC) for the treatment of factor Xa inhibitor (FXa-I)-associated bleeds, and observational studies lack important patient characteristics. We pursued this study to demonstrate the feasibility of acquiring relevant patient characteristics from electronic health records. Secondarily, we explored outcomes in patients with life-threatening FXa-I associated bleeds after adjusting for these variables. Methods We conducted a multicenter, chart review of 100 consecutive adult patients with FXa-I associated intracerebral hemorrhage (50) or gastrointestinal bleeding (50) treated with andexanet alfa or 4F-PCC. We collected demographic, clinical, laboratory, and imaging data including time from last factor FXa-I dose and bleed onset. Results Mean (SD) age was 75 (12) years; 34% were female. Estimated time from last FXa-I dose to bleed onset was present in most cases (76%), and patients treated with andexanet alfa and 4F-PCC were similar in baseline characteristics. Hemostatic efficacy was excellent/good in 88% and 76% of patients treated with andexanet alfa and 4F-PCC, respectively ( P = 0.29). Rates of thrombotic events within 90 days were 14% and 16% in andexanet alfa and 4F-PCC patients, respectively ( P = 0.80). Survival to hospital discharge was 92% and 76% in andexanet alfa and 4F-PCC patients, respectively ( P = 0.25). Inclusion of an exploratory propensity score and treatment in a logistic regression model resulted in an odds ratio in favor of andexanet alfa of 2.01 (95% confidence interval 0.67–6.06) for excellent/good hemostatic efficacy, although the difference was not statistically significant. Conclusion Important patient characteristics are often documented supporting the feasibility of a large observational study comparing real-life outcomes in patients with FXa-I-associated bleeds treated with andexanet alfa or 4F-PCC. The small sample size in the current study precluded definitive conclusions regarding the safety and efficacy of andexanet alfa or 4F-PCC in FXa-I-associated bleeds.

Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies

“…In this sense, the results of Ammar et al [ 15 ] showed that mortality was the same for both treatment groups at 38% and 36% for 4F-PCC and AA, respectively. Pham et al [ 22 ] and Lipski et al [ 19 ] also presented similar results. While Pham et al [ 22 ] observed an overall mortality of 34% and 21% for AA and 4F-PCC, respectively, Lipski et al [ 19 ] presented mortality data up to a follow-up period of 28 days (AA = 39.1; 4F-PCC: 40.4), although this period did not reveal any statistical differences in mortality.…”

“…In contrast, in the data of Vestal et al [ 24 ], Pham et al [ 22 ] and Oh et al [ 20 ], the number of thrombotic events was higher in the group receiving 4F-PCC, with more than 80% of them related to cerebral ischemia and DVT. Lipski et al [ 19 ] also reported a greater number of thromboembolic events with the use of 4F-PCC (8 events) than with AA (5 events), which were related to deep vein thrombosis/pulmonary embolism.…”

“…The results of Parsels et al [ 21 ], Vestal et al [ 24 ] and Pham et al [ 22 ] also showed no difference in cerebral hemorrhage volume after 12 and 24 h of treatment (AA vs. 4F-PCC). Oh et al [ 20 ] also came to similar conclusions as previous studies.…”

“…Barra et al [ 16 ] reported a case series of patients with intracranial hemorrhage associated with the use of apixaban or rivaroxaban treated with Andexanet alfa or 4F-PCC, and that treatment with AA achieved hemostatic efficacy (defined as a ≤35% increase in the thickness of the subarachnoid or subdural hematoma or the volume of intracerebral hemorrhage). These data are important because different studies have different methods for evaluating hemostatic efficacy [ 14 , 15 , 17 , 19 , 20 , 21 , 22 ]; if the methods were standardized, we believe the results of the analyses might represent a different outcome.…”