The Risk of Major Bleeding With Apixaban Administration in Patients With Acute Kidney Injury.

BACKGROUND: Apixaban is eliminated by the kidneys and in acute kidney injury (AKI) there is potential for an increase in apixaban exposure and bleeding events. In one instance, data have shown higher than normal bleed risk in patients with AKI, unless calibrated anti-factor Xa monitoring is used, which is not widely available. OBJECTIVE: To evaluate bleeding with apixaban administration to hospitalized patients with an AKI in an unmonitored real-world scenario. METHODS: We conducted a retrospective study of patients admitted to a large urban academic teaching hospital from April 2015 to March 2022, who received apixaban for venous thromboembolism or nonvalvular atrial fibrillation (NVAF). The primary outcome evaluated major bleeding when apixaban was administered to patients with or without an AKI. RESULTS: A total of 232 patients were evaluated (116 per group). Most patients (79.7%) were on apixaban for NVAF, 32.7% had chronic kidney disease, 58.2% were on a medication increasing bleed risk, and HAS-BLED score was a median of 2 in both groups. No differences were noted between groups for bleeding (AKI group 7.8% vs non-AKI 3.4%; P = 0.15), and on regression analysis, coadministration of a P2Y12 inhibitor was predictive of major bleeding (odds ratio = 5.9; 95% confidence interval = 1.4-23.6). CONCLUSION AND RELEVANCE: Although no differences between groups were noted, apixaban use in the AKI group resulted in a higher than normally reported incidence of apixaban-associated major bleeding, and concomitant antiplatelet use increased bleed risk as well. Cautious use of apixaban and further investigation with larger studies are warranted in this area.

Appropriateness of Pharmacologic Thromboprophylaxis Prescribing Based on Padua Score Among Inpatient Veterans.

Background: Hospitalized patients are at increased risk of developing venous thromboembolism (VTE). The Padua Prediction Score (PPS) was developed to help quantify the risk of VTE for hospitalized patients and guide prescribing of pharmacologic thromboprophylaxis. This study aims to assess whether PPS embedded within an admission order set was utilized appropriately to prescribe or withhold pharmacologic thromboprophylaxis. Methods: This single center, retrospective observational cohort study evaluated adult patients aged ≥ 18 years between June 2017 and June 2020. A random sample of 250 patient charts meeting inclusion criteria were reviewed to calculate PPSs, and clinician notes were reviewed for documentation as to whether thromboprophylaxis was given or withheld appropriately based on the PPS. A second cohort of patients admitted within the study period meeting inclusion criteria and readmitted for VTE within 45 days of discharge were evaluated to determine appropriateness of inpatient VTE thromboprophylaxis during index hospitalization based on the PPS. Results: Of the 250 patients examined, 118 (47.2%) had a PPS < 4 on admission. Of the 118 patients, 58 (49.2%) were inappropriately prescribed pharmacologic thromboprophylaxis administered within 24 hours of admission. The clinical rationale for giving thromboprophylaxis when not indicated was provided for only 2 (3.4%) of the 58 patients. Of the 132 patients with a PPS ≥ 4, 11 (8.3%) had thromboprophylaxis appropriately withheld and for 33 (25.0%) it was inappropriately withheld. A total of 88 (66.7%) patients received thromboprophylaxis as indicated by a PPS ≥ 4. Conclusions: Despite the inclusion of the PPS calculator in the facility's admission order set, this study showed pharmacologic thromboprophylaxis was frequently inappropriately given or withheld. This suggests written protocols and order sets may not be solely sufficient to ensure appropriate VTE prophylaxis in actual practice. Incorporation of additional tools, such as dashboards and scorecards, should be explored.

Factors Associated With Prolonged Antibiotic Use in the Setting of Suspected Pneumonia and Negative Bronchoalveolar Lavage Cultures.

Background: Diagnostic criterion for pneumonia includes clinical data and bronchoalveolar lavage cultures (BALCx) to identify pathogens. Although ~60% of BALCx are negative, there may be reluctance to discontinue antibiotics, leading to prolonged antibiotic use (PAU). Objective: The purpose of this study is to compare outcomes of subjects with negative BALCx with PAU versus without prolonged antibiotic use (nPAU). Methods: A retrospective cohort study was conducted including subjects admitted to the intensive care unit (ICU), with suspected pneumonia, and negative BALCx. Data were compared based on length of exposure to antibiotics, PAU (antibiotics >4 days) versus nPAU (antibiotics <4 days). Results: A total of 128 subjects were included, 57 in the PAU group and 71 in the nPAU group. Baseline demographics were similar between groups. Severity of illness measured by multiple organ dysfunction scores at time of bronchoalveolar lavage (BAL) collection to final result showed a statistically significant decrease in the PAU group but not in the nPAU group. No differences were found in ICU days, ventilator-free days, or mortality; however, length of stay was longer for PAU (23 vs. 17, p = .04). In the PAU group, there were fewer BALCx results of "no growth" (23% vs. 45%, p = .04), more positive gram stains (83% vs. 60%, p = .01) and more positive non-BALCx (40% vs. 14%, p = .01). In a multivariate analysis, factors associated with PAU were positive BAL gram stains (adjusted odds ratio [aOR] 3.1, p = .037) and positive non-BALCx (aOR 4.7, p = .002). Conclusion: For subjects with suspected pneumonia and negative BALCx, positive non-BALCx and positive BALCx gram stain influenced the length of exposure of antibiotics.

Inclusion in limited distribution drug network reduces time to dalfampridine access in patients with multiple sclerosis at a health-system specialty pharmacy.

BACKGROUND: Dalfampridine improves walking speed in patients with multiple sclerosis (MS), but accessing specialty medications such as dalfampridine can be hindered by insurance restrictions, high costs, and limited distribution networks (LDNs) imposed by manufacturers. Some integrated health-systems specialty pharmacies (HSSPs) embed pharmacists in clinics and dispense medications from their internal pharmacies if included within the LDN. OBJECTIVE: To assess access to dalfampridine in patients at an HSSP before and after gaining admission to the LDN. METHODS: This study was conducted at Vanderbilt Specialty Pharmacy (VSP), an integrated HSSP at Vanderbilt University Medical Center (VUMC) with 2 clinical pharmacists embedded in the MS clinic. VSP gained access to the dalfampridine LDN on May 1, 2018, at which time the embedded pharmacists began to manage the comprehensive therapy initiation process. We performed a retrospective review of adult patients with MS who were prescribed dalfampridine from March 2010 to December 2018. Eligible prescriptions were new starts (no previous use) or restarts (after previous use and discontinuation). Prescriptions were classified as pre-VSP and post-VSP, which differentiates before and after VSP gained access to dispense dalfampridine. Study outcomes were insurance approval, initiation of therapy, and time from treatment decision to medication access. We used a proportional odds logistic regression model for time to medication access using the following covariates: pre-VSP versus post-VSP time period, insurance prior authorization (PA) denied versus approved/not needed, and baseline timed 25-foot walk. RESULTS: We included 262 patients and 290 prescriptions (260 pre-VSP and 30 post-VSP). In pre-VSP and post-VSP prescriptions, 97% were approved by insurance, and 93% of patients started therapy. Median time to medication access was 22 days (IQR = 11-45) for pre-VSP prescriptions and 1 day (IQR = 0-3) for post-VSP prescriptions. In the proportional odds logistic regression model, the odds of having a longer medication access time were significantly higher for pre-VSP prescriptions (OR = 83.219, P < 0.001) and prescriptions whose PA was initially denied (OR = 9.50, P < 0.001); 25-foot walk time was not significant (OR = 0.95, P = 0.277). CONCLUSIONS: After obtaining access to dispense dalfampridine, the time to access therapy was reduced, suggesting that LDNs delay patient access to therapy at HSSPs. DISCLOSURES: No funding was provided for this study. The authors have no conflicting interests to disclose. Preliminary results have been previously presented at the American Society of Health-Systems Pharmacy Midyear Meeting in December 2019, the Vanderbilt Health Systems Specialty Pharmacy Outcomes Research Summit in August 2020, and the National Association of Specialty Pharmacy Annual Meeting in September 2020.