The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage.

OBJECTIVE: Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH). METHODS: A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020. Patients were included in the study if they received reversal with either andexanet alfa or 4F-PCC. RESULTS: Eighty-nine patients were included in the study. There was no statistically significant difference in 30-day mortality between patients who received andexanet alfa or 4F-PCC (52% vs. 35%, P  = 0.14). Radiographic stability of bleed was identified in 57% of patients receiving andexanet alfa vs. 58% of patients receiving 4F-PCC ( P  = 0.93). Median length of stay was not different between the andexanet alfa and 4F-PCC populations (7 days [IQR 6 - 12] vs. 6 days [IQR 3-12], P  = 0.66). Median cost of reversal agent was higher in patients receiving andexanet alfa compared to 4F-PCC ($15 000 [IQR 15 000-$27 000] vs. $11 650 [IQR $8567-$14 149]). CONCLUSION: Among patients with life-threatening intracranial hemorrhage in the setting of DOAC therapy, no clinical differences were observed with respect to selection of reversal agent. Prothrombin complex concentrates remain a viable alternative to reversal of DOAC therapy though multicenter, randomized, prospective studies are needed to further evaluate the role of 4F-PCC in the reversal of DOAC therapy.

Safety and effectiveness of albuterol solutions with and without benzalkonium chloride when administered by continuous nebulization.

PURPOSE: The results of a study to determine if rates of poor response differ in patients receiving continuous nebulized albuterol (CNA) therapy with or without the preservative benzalkonium chloride are presented. METHODS: A retrospective analysis of the records of all patients who received CNA therapy at a large academic medical center from July 2015 to January 2016 was conducted. Data from patient evaluations performed before and after a change to benzalkonium chloride-containing albuterol were collected. The primary outcome was the rate of poor patient response, defined as a composite endpoint. Secondary outcomes included duration of therapy, dosing requirements, and duration of supplemental oxygen therapy. RESULTS: There was no significant difference in rates of poor response between patients exposed (n = 80) and patients not exposed (n = 48) to benzalkonium chloride (16% and 17%, respectively; p = 0.95). The cohort not exposed to benzalkonium chloride had a median CNA duration of 7.0 hours, as compared with 10.5 hours for the cohort exposed to benzalkonium chloride, but this difference was not significant (p = 0.19). There were no significant differences between the benzalkonium chloride-exposed and nonexposed cohorts in the maximum dosing requirement (12.6 mg/hr versus 12.8 mg/hr, p = 0.89) or median duration of supplemental oxygen use (27.5 hours versus 16.5 hours, p = 0.77). CONCLUSION: A study of hospitalized patients receiving CNA detected no significant difference in the frequency of poor response to therapy between groups receiving benzalkonium chloride-free versus benzalkonium chloride-containing albuterol products.