MD; for the TIMI 11B (Thrombolysis In Myocardial Infarction) and ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) InvestigatorsBackground-Two phase III trials of enoxaparin for unstable angina/non-Q-wave myocardial infarction have shown it to be superior to unfractionated heparin for preventing a composite of death and cardiac ischemic events. A prospectively planned meta-analysis was performed to provide a more precise estimate of the effects of enoxaparin on multiple end points. Methods and Results-Event rates for death, the composite end points of death/nonfatal myocardial infarction and death/nonfatal myocardial infarction/urgent revascularization, and major hemorrhage were extracted from the TIMI 11B and ESSENCE databases. Treatment effects at days 2, 8, 14, and 43 were expressed as the OR (and 95% CI) for enoxaparin versus unfractionated heparin. All heterogeneity tests for efficacy end points were negative, which suggests comparability of the findings in TIMI 11B and ESSENCE. Enoxaparin was associated with a 20% reduction in death and serious cardiac ischemic events that appeared within the first few days of treatment, and this benefit was sustained through 43 days. Enoxaparin's treatment benefit was not associated with an increase in major hemorrhage during the acute phase of therapy, but there was an increase in the rate of minor hemorrhage. Conclusions-The accumulated evidence, coupled with the simplicity of subcutaneous administration and elimination of the need for anticoagulation monitoring, indicates that enoxaparin should be considered as a replacement for unfractionated heparin as the antithrombin for the acute phase of management of patients with high-risk unstable angina/non-Q-wave myocardial infarction. (Circulation. 1999;100:1602-1608.)

No abstract

STUDY OBJECTIVE As the incidence rate of renal impairment is 2–10% for patients treatment with high-dose methotrexate , and renal impairment develops in 0–12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination. DESIGN Pooled analysis of efficacy data from four multicenter, single-arm, compassionate-use clinical trials using protocols from 1993–2007. PATIENTS Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1 µmol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement. MEASUREMENTS AND MAIN RESULTS Efficacy was defined as rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, with a concentration of 1 µmol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20 years (range 5 wks–84 yrs). Osteosarcoma (36%), non-Hodgkin’s lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7 µmol/L. At the first (median 15 min) through the last (median 40 hrs) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. Sixty-four percent of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5 days after glucarpidase administration. CONCLUSION Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients.

Patients treated with foamed liquid sclerosants are commonly exposed to cerebrovascular gas bubbles. In this series of 60 high-risk patients with MCA bubble emboli during or after treatment with ultra-low nitrogen polidocanol endovenous microfoam, there was no evidence of cerebral or cardiac microinfarction. The results of this study cannot be generalized to foams compounded using bedside methodologies, since the composition of these foams is substantially different.