Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhages.

BACKGROUND: Existing research recommends either andexanet alfa (AA) or four-factor prothrombin complex concentrate (4F-PCC) as an antidote for major bleeding events due to apixaban or rivaroxaban. Currently, there is limited published research that directly compares the risks and benefits of the two agents in patients with oral factor Xa inhibitor related traumatic and spontaneous intracerebral hemorrhages. Additional head-to-head data is needed to support favoring either AA or 4F-PCC when it comes to efficacy, safety, and cost. METHODS: A retrospective chart review was conducted to assess patients admitted to a multi-center healthcare system and a stand-alone teaching hospital in central Florida from June 2016 to December 2020. Patients included in the study were at least 18 years of age, taking apixaban or rivaroxaban prior to admission, had radiographical evidence of an intracranial hemorrhage, and received either AA or 4F-PCC as a reversal agent. The primary outcome analyzed was the level of excellent hemostasis achieved, based on a standardized rating system for effective hemostasis defined by the International Society of Thrombosis and Hemostasis (ISTH), after administration of AA or 4F-PCC. Secondary outcomes analyzed included changes in the initial hemorrhage volume as reported on computed tomography (CT) scan and at 12 to 24 h post treatment, rate of thromboembolic events, rate of inpatient mortality, and total cost of treatment after AA or 4F-PCC administration. RESULTS: A total of 109 patients were included in the study with 47 in the AA group (43.1%) and 62 in the 4F-PCC group (56.9%). There were no statistically significant differences between AA and 4F-PCC in terms of the primary and secondary outcomes with the exception of total cost of treatment. The level of excellent hemostasis achieved after reversal administration of AA was seen in 27 patients (71.1%) and 41 patients (70.7%) after 4F-PCC administration (p = 1, p adjusted = 0.654 after controlling for age, ICH score, regional mass effect, and midline shift). There was no statistically significant difference in the median percentage change in hemorrhagic volume from baseline to 12-24 h after reversal treatment (0 [-0.17--0.24] vs. 0 [-0.021-0.29], p = 0.439, adjusted p = 0.601) in the AA and 4F-PCC groups, respectively. The total incidence of thromboembolic events (4 [8.5%] vs. 6 [9.7%], p = 1, adjusted p = 0.973) and rate of inpatient mortality was similar between the two groups (16 [34.0%] vs. 13 [21.0%], p = 0.134, adjusted p = 0.283). A statistically significant difference was observed with the total cost of reversal treatment: $23,602 for treatment with AA and $6692 for treatment with 4F-PCC. CONCLUSIONS: No statistically significant differences were identified in primary or secondary outcomes between the two agents with the exception of total treatment cost. There is insufficient evidence based on this study to recommend AA over 4F-PCC for patients with intracranial hemorrhages associated with the use of apixaban or rivaroxaban.

Disparities in hemodynamic resuscitation of the obese critically ill septic shock patient.

BACKGROUND: With a growing obesity epidemic, the approach to care of this patient remains controversial and in many circumstances different than the general population. Appropriate hemodynamic support, although still controversial, remains a cornerstone of septic shock therapy. Catecholamines are currently recommended by guidelines without a preferred dosing strategy. However, the use of weight-based (µg kg-1 min-1) or nonweight-based (µg/min) vasopressor drip rates may impact patient care in these populations. METHODS: A multicenter retrospective chart review was conducted. Patients receiving nonweight-based catecholamine infusions for septic shock were grouped into nonobese (n = 112) or obese (n = 196), and evaluated based on hemodynamic resuscitation. For the primary outcome, groups were analyzed for the requirement of a secondary hemodynamic support agent to obtain a goal mean arterial pressure of greater than or equal to 65 mm Hg. Secondary outcomes included an evaluation of time to a secondary hemodynamic support agent, time to hemodynamic stability (HDS), ability to obtain HDS at 24 hours, and death due to cardiovascular collapse. RESULTS: With the exception of weight and sex, baseline characteristics were similar among groups. Early resuscitative fluids were given at a lower weight based, but not total volume dose in the obese group (nonobese, 34.8 mL/kg vs obese, 22.4 mL/kg; P < .0001). The primary end point of addition of any secondary hemodynamic support agent was significantly greater in obese patients when adjusted for institution (nonobese, 19% vs obese, 27%; adjusted odds ratio, 0.42; 95% confidence interval, 0.23-0.77). Time to HDS was also prolonged (nonobese, 3.5 hours vs obese, 5.3 hours; P = .006). CONCLUSION: This study calls into question the adequacy of a nonweight-based approach to hemodynamic support of critically ill obese patients. This strategy seems to result in less aggressive, lower weight-based vasopressor and fluid doses, and more diverse approach than their nonobese counterparts.