Among patients hospitalized with life-threatening or uncontrolled bleeding under treatment with direct factor Xa inhibition, anticoagulation reversal with andexanet alfa (Andexxa) was associated with low mortality rates. These promising results have multiple limitations, particularly the lack of definition on bleeding severity.
One of the studies testing the new antidote used propensity-score matching, and there were lower 30-day mortality rates overall compared with a prothrombin complex concentrate. There was also a reduction in intracranial hemorrhage and gastrointestinal bleeding rates.
In the other study, in-hospital mortality was also lower with andexanet alfa compared with different strategies for anticoagulation reversal (fresh frozen plasma, coagulation factors, etc.).
Both studies had originally been accepted for presentation at the American College of Cardiology 2020 Scientific Session, which was finally held virtually due to the COVID-19 pandemic.
Before May 2018, when the US Food and Drug Administration approved andexanet alfa, there was no specific treatment to revert the effect of direct factor Xa inhibitors, although the off-label use of different prothrombin complex concentrates was common. The analysis was conducted in patients receiving rivaroxaban and apixaban.
After propensity-score matching, there were 322 patients who received andexanet alfa and 88 patients who received a prothrombin complex concentrate. A third of patients experienced intracranial hemorrhage, a fourth experienced gastrointestinal bleeding, and the rest presented other types of bleeding.
Andexanet alfa was associated with lower 30-day mortality in the overall population (14.60% vs. 34.09%; risk ratio [RR]: 0.43; 95% confidence interval [CI]: 0.29-0.63), as well as in the subgroups with intracranial hemorrhage (15.31% vs. 48.94%; RR: 0.31; 95% CI: 0.20-0.48) and gastrointestinal bleeding (12.20% vs. 25.00%; RR: 0.49; 95% CI: 0.21-1.16).
These results have several limitations, but in the absence of head-to-head randomized trials, they are the best currently available data.
Original Title: 30-day mortality following andexanet alfa in ANNEXA-4 compared with prothrombin complex concentrate (PCC) therapy in the ORANGE study for life threatening non-vitamin K oral anticoagulant (NOAC) related bleeding.
Reference: Cohen A et al. ACC 2020 virtual.
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