A Retrospective Analysis of Sacubitril/Valsartan in Heart Failure and Chronic Kidney Disease.

Background: Sacubitril/valsartan has demonstrated benefit for patients with heart failure (HF); however, patients with advanced stages of chronic kidney disease (CKD) as defined by the National Kidney Foundation have historically been underrepresented in landmark HF trials. Objective: The goal of this study is to examine the safety and efficacy of sacubitril/valsartan in patients with HF and concomitant CKD stages III to V. Methods: This multicenter, retrospective, observational study included adult patients with HF and CKD stages III to V prescribed sacubitril/valsartan during hospital admission or upon discharge from January 2017 through March 2022. The primary outcome was the comparison of estimated glomerular filtration rate (eGFR) from baseline to 90 days. Key secondary outcomes included the comparison of the ejection fraction (EF) at 180 days, the rate of all-cause- and HF-related readmissions within 30 days, and adverse events. Results: Fifty patients were included in the analysis, with most patients (56%) having CKD stage IIIa. There was no difference in eGFR between baseline and 90 days (45.3 (11.2) mL/min/1.73 m2 vs 45.5 (18.6) mL/min/1.73 m2; P = 0.91). EF improved between baseline and 180 days (median 22.5% [17.5-27.5] vs 30.0% [22.5-42.5]; P < 0.001). Three patients (6%) were rehospitalized within 30 days for HF-related causes. There were 6 episodes (12%) of hyperkalemia greater than 5.0 milliequivalents per liter (mEq/L), and 2 episodes (4%) greater than 5.5 mEq/L. Conclusion: There was no significant difference in eGFR from baseline to 90 days in patients with HF and CKD prescribed sacubitril/valsartan during hospitalization, though there was an observed increase in EF.

Comparison of Bivalirudin Versus Unfractionated Heparin for Anticoagulation in Adult Patients on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.

Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Evidence Based Review of Pharmacotherapy for Opioid-Induced Constipation in Noncancer Pain.

OBJECTIVE: To summarize and evaluate the existing literature regarding medications to treat opioid-induced constipation (OIC) in patients with chronic noncancer pain (CNCP). DATA SOURCES: PubMed, EMBASE, and Web of Science were searched using the following terms: constipation, opioid, chronic, pain, noncancer, nonmalignant, methylnaltrexone, alvimopan, lubiprostone, naloxegol, and naldemedine. STUDY SELECTION AND DATA EXTRACTION: The search was limited to randomized controlled trials reporting human outcomes. Data extracted included the following: study design, population, intervention, control, outcomes related to OIC and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool. DATA SYNTHESIS: After assessment, 16 of the 190 studies were included: methylnaltrexone (n = 4), naloxegol (n = 3), naldemedine (n = 2), lubiprostone (n = 3), and alvimopan (n = 4). Lubiprostone was the only nonperipherally acting µ-opioid receptor antagonist included. Only 1 study (naloxegol) used "usual care" (nonstudy laxative) rather than placebo as a comparator. Placebo-controlled trials demonstrated benefit for methylnaltrexone, naloxegol, naldemedine, and lubiprostone, with conflicting evidence for alvimopan. No data suggest that one agent is better than another. Overall risk of bias across all studies was low to moderate. CONCLUSIONS: With risk of bias determined to be low to moderate, published data to date suggest that methylnaltrexone, naloxegol, and naldemedine may be appropriate to treat OIC in patients with CNCP.