losartan-potassium and Aneurysm--Ruptured

Topics: Aneurysm, Ruptured; Epoetin Alfa; Erythropoietin; Humans; Neuroprotective Agents; Recombinant Proteins; Subarachnoid Hemorrhage

In a previous randomized controlled trial, the authors demonstrated that acute erythropoietin (EPO) therapy reduced severe vasospasm and delayed ischemic deficits (DIDs) following aneurysmal subarachnoid hemorrhage. In this study, the authors aimed to investigate the potential interaction of neurovascular protection by EPO with age, sepsis, and concurrent statin therapy.. The clinical events of 80 adults older than 18 years and with < 72 hours of aneurysmal subarachnoid hemorrhage, who were randomized to receive 30,000 U of intravenous EPO-beta or placebo every 48 hours for a total of 3 doses, were analyzed by stratification according to age (< or > or = 60 years), sepsis, or concomitant statin therapy. End points in the trial included cerebral vasospasm and impaired autoregulation on transcranial Doppler ultrasonography, DIDs, and unfavorable outcome at discharge and at 6 months measured with the modified Rankin Scale and Glasgow Outcome Scale. Analyses were performed using the t-test and/or ANOVA for repeated measurements.. Younger patients (< 60 years old) or those without sepsis obtained benefits from EPO by a reduction in vasospasm, impaired autoregulation, and unfavorable outcome at discharge. Compared with nonseptic patients taking EPO, those with sepsis taking EPO had a lower absolute reticulocyte count (nonsepsis vs sepsis, 143.5 vs. 105.8 x 10(9)/L on Day 6; p = 0.01), suggesting sepsis impaired both hematopoiesis and neurovascular protection by EPO. In the EPO group, none of the statin users suffered DIDs (p = 0.078), implying statins may potentiate neuroprotection by EPO.. Erythropoietin-related neurovascular protection appears to be attenuated by old age and sepsis and enhanced by statins, an important finding for designing Phase III trials.

Topics: Age Factors; Aneurysm, Ruptured; Clinical Trials, Phase II as Topic; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Erythropoietin; Glasgow Outcome Scale; Hematopoiesis; Homeostasis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperemia; Intracranial Aneurysm; Middle Aged; Neuroprotective Agents; Randomized Controlled Trials as Topic; Recombinant Proteins; Sepsis; Subarachnoid Hemorrhage; Ultrasonography, Doppler, Transcranial; Vasospasm, Intracranial