Direct Oral Anticoagulants Versus Warfarin for Treatment of Thrombosis or Atrial Fibrillation in Patients With Cirrhosis: A Retrospective Cohort Study.

BACKGROUND: Evidence for direct oral anticoagulants (DOACs) in patients with cirrhosis is limited. Few patients with Child-Turcotte-Pugh (CTP) class B and C cirrhosis have been studied. OBJECTIVE: To compare major bleeding rates in patients with cirrhosis receiving a DOAC versus warfarin. METHODS: A retrospective cohort study was conducted in adults with cirrhosis receiving a DOAC versus warfarin for venous thromboembolism, portal-vein thrombosis, or atrial fibrillation. The primary outcome was the rate of major bleeding. Secondary outcomes included time to major bleeding, clinically relevant nonmajor bleeding, all bleeding, gastrointestinal bleeding, intracranial bleeding, and new thromboembolic events. The study was approved by the Ochsner Health System Institutional Review Board. RESULTS: A total of 44 patients receiving a DOAC and 41 patients receiving warfarin were included. Major bleeding occurred in 4 patients receiving a DOAC and 6 patients receiving warfarin (9.1% vs 14.6%; P = 0.881). Rates of major bleeding were similar in 24 DOAC and 17 warfarin patients with CTP Class B (4.2% vs 17.6%; P = 0.37) and 8 DOAC and 9 warfarin patients with CTP Class C (37.5% vs 11.1%; P = 0.41) cirrhosis. Secondary bleeding and efficacy outcomes were similar between cohorts. The study was limited by a small sample size. CONCLUSION AND RELEVANCE: Treatment with DOACs in patients with cirrhosis was associated with a similar rate of major bleeding compared with warfarin. Inclusion of CTP class C patients in future studies remains valuable to evaluate safety and efficacy of DOACs in this population.

Safety and Efficacy of Apixaban Versus Warfarin in Patients With Advanced Chronic Kidney Disease.

BACKGROUND: Because of a lack of comparative data on anticoagulant use in the advanced chronic kidney disease (CKD) population, guidelines recommend warfarin for atrial fibrillation and venous thromboembolism (VTE) treatment in these patients. However, apixaban has specific dosing recommendations in CKD leading to use in clinical practice. OBJECTIVE: To evaluate major bleeding, stroke, and thromboembolism rates in patients with CKD stage 4, stage 5, and dialysis on apixaban or warfarin therapy. METHODS: This was a retrospective cohort study of patients with advanced CKD receiving apixaban or warfarin. The primary outcome was the occurrence of major bleeding at 3 months after enrollment. Secondary outcomes included occurrence of major bleeding, occurrence of ischemic stroke, and recurrence of VTE at 3 to 6 and 6 to 12 months. RESULTS: A total of 604 patients were included in the analysis. The percentage of apixaban and warfarin patients with a major bleed at 0 to 3, 3 to 6, and 6 to 12 months were 8.3% versus 9.9% ( P=0.48), 1.4% versus 4% ( P=0.07), and 1.5% versus 8.4% ( P<0.001), respectively. There were no differences in rates of ischemic stroke or recurrent VTE at any time period. Conclusion and Relevance: Patients with advanced CKD taking apixaban had similar bleeding rates at 3 months compared with those taking warfarin. However, those who continued therapy had higher major bleeding rates with warfarin between 6 and 12 months. This study provides knowledge on the effects of a direct oral anticoagulant in a population that was excluded from all major trials.

Evaluation of a Once/Day Tobramycin Regimen to Achieve Target Concentrations in Adult Patients with Cystic Fibrosis.

STUDY OBJECTIVE: To evaluate the success of an initial tobramycin dosing regimen to achieve target peak and trough concentrations in adult patients with pulmonary exacerbations of cystic fibrosis (CF). DESIGN: Retrospective single-center medical record review. SETTING: Large tertiary care academic medical center. PATIENTS: A total of 186 patient encounters where 112 patients with CF were treated for acute pulmonary exacerbations with 10 mg/kg/day of tobramycin between January 1, 2009, and December 5, 2014. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, clinical characteristics, tobramycin data, and pharmacokinetic variables were collected. The primary outcome evaluated the success of the initial tobramycin dosing regimen in attaining the target peak concentration. Secondary end points were achievement of the target trough concentration, achievement of combined peak and trough targets, and incidence of nephrotoxicity. Bivariate and multivariate analyses were performed to evaluate factors associated with achieving target concentrations. Of the 186 patient encounters, 41% achieved the target peak with the first dosing regimen, 62% achieved a target trough, and 23% achieved the target peak and trough. Nephrotoxicity occurred in 10% of patient encounters. A body mass index (BMI) of 18.5-24.9 kg/m(2) was associated with higher odds of meeting the target peak compared with a BMI lower than 18.5 kg/m(2) (odds ratio [OR] 24.5; 95% confidence interval [CI] 5.2-117.2). Conversely, a BMI of 18.5-24.9 kg/m(2) was associated with lower odds of attaining the target trough compared with a BMI lower than 18.5 kg/m(2) (OR 0.16; 95% CI 0.05-0.56). Higher volume of distribution and elimination rate constants (Kel ) were associated with significantly lower odds of achieving the target peak. In addition, higher Kel values were associated with significantly higher odds of achieving the target trough. CONCLUSIONS: The current initial tobramycin regimen did not achieve target serum tobramycin concentrations reliably. Optimization of the initial CF tobramycin dosing regimen is warranted.