Droxidopa in the Management of Hepatorenal Syndrome.

PurposeHepatorenal syndrome (HRS) is renal dysfunction associated with the hemodynamic consequences of advanced liver disease and cirrhosis. HRS is associated with a high mortality, and there remain high failure rates with first-line therapy aimed at improving perfusion. We report the use of droxidopa, an oral norepinephrine precursor, to aid in the management of HRS-AKI refractory to first-line therapy. Summary: A 51-year-old Caucasian male with alcohol-related cirrhosis presented with 1-week history of pre-syncope and falls. He was found to have acute kidney injury meeting diagnostic criteria of HRS based on absence of identifiable contributing factors. After no response to volume expansion, medical management was initiated with midodrine and octreotide and eventually escalated to norepinephrine intravenous infusion. The patient's renal function and urine output improved initially on norepinephrine, but worsened when attempting to wean to a suitable outpatient regimen, becoming dependent upon norepinephrine. On day 13 of hospitalization, droxidopa was initiated at a dose of 100 mg three times daily and titrated to a dose of 400 mg three times daily. Norepinephrine infusion was weaned and discontinued on day 16 of hospitalization. The patient remained hemodynamically stable and was able to be discharged on droxidopa 400 mg three times daily, midodrine 20 mg three times day, and octreotide 200 mcg three times daily. Conclusion: Droxidopa, an oral norepinephrine precursor, presents a novel adjunctive agent for management of HRS refractory to first-line medical management.

Effectiveness and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients with Acute Venous Thromboembolism.

STUDY OBJECTIVE: Studies on the use of direct oral anticoagulants (DOACs) in obese patients are limited. Current guidelines advise against DOAC use in patients with a body weight more than 120 kg or body mass index higher than 40 kg/m2 . Therefore, the aim of this study was to evaluate the effectiveness and safety of DOACs versus warfarin for the treatment of acute venous thromboembolism (VTE) in obese patients. DESIGN: Retrospective matched cohort study. SETTING: Integrated delivery system of 40 academic, community, and specialty hospitals. PATIENTS: A total of 1840 adults with a primary admission diagnosis of acute VTE who received a DOAC (apixaban, dabigatran, or rivaroxaban [632 patients] or warfarin [1208 patients]) while hospitalized between January 1, 2011, and October 1, 2015, and who had a body weight more than 100 kg and less than 300 kg, were included. Patients in the warfarin group were matched in a 2:1 ratio to patients who received a DOAC based on history of VTE, chronic kidney disease, race, and age. MEASUREMENTS AND MAIN RESULTS: The primary outcome was recurrence of VTE within 12 months of the index admission date. Secondary outcomes included occurrence of pulmonary embolism (PE) and deep vein thrombosis (DVT) events separately within the study time frame, as well as bleeding within 12 months of the index admission date. No significant difference in the recurrence of VTE was observed between patients who received a DOAC compared with those who received warfarin (6.5% vs 6.4%, p=0.93). Likewise, no significant differences in the occurrence of PE and DVT were seen between the DOAC- and warfarin-treated patients (3.7% vs 3.8%, p=0.94, and 3% vs 3.5%, p=0.56, respectively). Bleeding occurred in 1.7% and 1.2% of patients in the DOAC and warfarin groups, respectively (p=0.31). CONCLUSION: To our knowledge, this is the largest clinical study to date showing that patients with obesity can be treated effectively and safely with a DOAC compared with warfarin for acute VTE. Thus DOACs should be considered a reasonable alternative to warfarin for treatment of acute VTE in obese patients.