Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Vancomycin area under the curve versus trough only guided dosing and the risk of acute kidney injury: Systematic review and meta-analysis.

Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus Guidelines recommended targeting trough concentrations but the 2020 Guidelines suggest monitoring vancomycin area under the curve (AUC) given the reduced risk of acute kidney injury (AKI) at similar levels of efficacy. This meta-analysis compares vancomycin-induced AKI incidence using AUC-guided dosing strategies versus trough-based monitoring. Literature was queried from Medline (Ovid), Web of Science, and Google Scholar from database inception through November 5, 2021. Interventional or observational studies reporting the incidence of vancomycin-induced AKI between AUC- and trough-guided dosing strategies were included. In the primary analysis, the Vancomycin Consensus Guidelines definition for AKI was used if reported; otherwise, the Risk, Injury, and Failure; and Loss, and End-stage kidney disease (RIFLE) or Kidney Disease Improving Global Outcomes (KDIGO) definitions were used. The incidence of nephrotoxicity was evaluated between the two strategies using a Mantel-Haenszel random-effects model, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses for adjusted ORs and AKI definitions were performed. Heterogeneity was identified using Cochrane's Q test and I2 statistics. A total of 10 studies with 4231 patients were included. AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies [OR 0.625, 95% CI (0.469-0.834), p = 0.001; I2  = 25.476]. A subgroup analysis of three studies reporting adjusted ORs yielded similar results [OR 0.475, 95% CI (0.261-0.863), p = 0.015]. Stratification by AKI definition showed a significant reduction in AKI with the Vancomycin Consensus Guidelines definition [OR 0.552, 95% CI (0.341-0.894), p = 0.016] but failed to find significance in the alternative definitions. Area under the curve-guided dosing strategies are associated with a lower incidence of vancomycin-induced AKI versus trough-guided dosing strategies (GRADE, low). Limitations included the variety of AKI definitions and the potential for confounding bias.