CSL112 (Apolipoprotein A-I [Human]) Strongly Enhances Plasma Apoa-I and Cholesterol Efflux Capacity in Post-Acute Myocardial Infarction Patients: A PK/PD Substudy of the AEGIS-I Trial.

INTRODUCTION: Cholesterol efflux capacity (CEC) is impaired following acute myocardial infarction (AMI). CSL112 is an intravenous preparation of human plasma-derived apoA-I formulated with phosphatidylcholine (PC). CSL112 is intended to improve CEC and thereby prevent early recurrent cardiovascular events following AMI. AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b study, designed to evaluate the hepatic and renal safety of CSL112. Here, we report an analysis of a pharmacokinetic (PK) and pharmacodynamic (PD) substudy of AEGIS-I. METHODS: AMI patients were stratified by renal function and randomized 3:3:2 to 4, weekly, 2-hour infusions of low- and high-dose (2 g and 6 g) CSL112, or placebo. PK/PD assessments included plasma concentrations of apoA-I and PC, and measures of total and ABCA1-dependent CEC, as well as lipids/lipoproteins including high density lipoprotein cholesterol (HDL-C), non-HDL-C, low density lipoprotein cholesterol (LDL-C), ApoB, and triglycerides. Inflammatory and cardio-metabolic biomarkers were also evaluated. RESULTS: The substudy included 63 subjects from AEGIS-I. CSL112 infusions resulted in rapid, dose-dependent increases in baseline corrected apoA-I and PC, which peaked at the end of the infusion (Tmax ≈ 2 hours). Similarly, there was a dose-dependent elevation in both total CEC and ABCA1-mediated CEC. Mild renal impairment did not affect the PK or PD of CSL112. CSL112 administration was also associated with an increase in plasma levels of HDL-C but not non-HDL-C, LDL-C, apoB, or triglycerides. No dose-effects on inflammatory or cardio-metabolic biomarkers were observed. CONCLUSION: Among patients with AMI, impaired CEC was rapidly elevated by CSL112 infusions in a dose-dependent fashion, along with an increase in apoA-I plasma concentrations. Findings from the current sub-study of the AEGIS-I support a potential atheroprotective benefit of CSL112 for AMI patients.

Anesthesia monitoring by registered nurses during cataract surgery: assessment of need for intraoperative anesthesia consultation.

PURPOSE: To assess the frequency and risk factors for intraoperative anesthesia consultation when performing cataract surgery monitored by registered nurses. SETTING: Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, USA. METHODS: This retrospective review was of 270 cataract surgeries performed under local anesthesia from April 1, 2002, to April 1, 2003. RESULTS: The American Society of Anesthesiologists (ASA) classification of each patient was determined: 1 patient was classified as ASA 1. One hundred fifty patients were classified as ASA 2. One hundred nineteen patients were classified as ASA 3. The anesthesiology department was consulted 24 times. Nineteen consultations involved patients who were ASA 3, and 5 consultations involved patients who were ASA 2 (P<.001). In most cases (23 of 24), the anesthesia service provided a consultation (eg, increase oxygen flow rate, clarification of electrocardiogram, start intravenous line, equipment repair) and left the nurses to continue to monitor the patient. In only 1 case (ASA 3), the anesthesia service converted the case to monitored anesthesia care and relieved the nurse to monitor the patient. CONCLUSIONS: In this study, monitoring of routine cataract surgery by registered nurses was associated with a low rate of intraoperative anesthesia consultation. Most consultations resulted in little intervention. The ASA classification appears predictive of the need for intraoperative anesthesia consultation.