E François Aldrich1, Randall Higashida2, Abdel Hmissi3, Elizabeth J Le1, R Loch Macdonald4,5, Angelina Marr3, Stephan A Mayer6, Sébastien Roux3, Nicolas Bruder7. 1. 1Department of Neurosurgery, University of Maryland, Baltimore, Maryland. 2. 2Department of Neurointerventional Radiology, University of California San Francisco Medical Center, San Francisco, California. 3. 3Global Clinical Development, Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland. 4. 4Department of Neurological Surgery, University of California San Francisco, Fresno, California. 5. 5Department of Surgery, University of Toronto, Ontario, Canada. 6. 6Department of Neurology, Henry Ford Neuroscience Institute, Wayne State School of Medicine, Detroit, Michigan; and. 7. 7Department of Anesthesia and Critical Care, Hôpital de la Timone, Aix-Marseille Université, Marseille, France.
Abstract
OBJECTIVE:Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade. METHODS: In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)-2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively. Patients without and with thick, diffuse SAH (≥ 4 mm thick and involving ≥ 3 basal cisterns) on admission CT scans were compared. Clot size was centrally adjudicated. All-cause mortality and vasospasm-related morbidity at 6 weeks and Glasgow Outcome Scale-Extended (GOSE) scores at 12 weeks after aSAH were assessed. The effect of the thick and diffuse cisternal aSAH on vasospasm-related morbidity and mortality, and on poor clinical outcome at 12 weeks, was evaluated using logistic regression models. RESULTS: Overall, 294 patients (51.4%) had thick and diffuse aSAH. Compared to patients with less hemorrhage burden, these patients were older (median age 55 vs 50 years) and more often had World Federation of Neurosurgical Societies (WFNS) grade III-V SAH at admission (24.1% vs 16.5%). At 6 weeks, all-cause mortality and vasospasm-related morbidity occurred in 36.1% (95% CI 30.6%-41.8%) of patients with thick, diffuse SAH and in 14.7% (95% CI 10.8%-19.5%) of those without thick, diffuse SAH. Individual event rates were 7.5% versus 2.5% for all-cause death, 19.4% versus 6.8% for new cerebral infarct, 28.2% versus 9.4% for delayed ischemic neurological deficit, and 24.8% versus 10.8% for rescue therapy due to cerebral vasospasm, respectively. Poor clinical outcome (GOSE score ≥ 4) was observed in 32.7% (95% CI 27.3%-38.3%) and 16.2% (95% CI 12.1%-21.1%) of patients with and without thick, diffuse SAH, respectively. CONCLUSIONS: In a large, centrally adjudicated population of patients with aSAH, WFNS grade at admission and thick, diffuse SAH independently predicted vasospasm-related morbidity and poor 12-week clinical outcome. Patients with thick, diffuse cisternal SAH may be an important cohort to target in future clinical trials of treatment for vasospasm.
RCT Entities:
OBJECTIVE:Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade. METHODS: In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)-2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively. Patients without and with thick, diffuse SAH (≥ 4 mm thick and involving ≥ 3 basal cisterns) on admission CT scans were compared. Clot size was centrally adjudicated. All-cause mortality and vasospasm-related morbidity at 6 weeks and Glasgow Outcome Scale-Extended (GOSE) scores at 12 weeks after aSAH were assessed. The effect of the thick and diffuse cisternal aSAH on vasospasm-related morbidity and mortality, and on poor clinical outcome at 12 weeks, was evaluated using logistic regression models. RESULTS: Overall, 294 patients (51.4%) had thick and diffuse aSAH. Compared to patients with less hemorrhage burden, these patients were older (median age 55 vs 50 years) and more often had World Federation of Neurosurgical Societies (WFNS) grade III-V SAH at admission (24.1% vs 16.5%). At 6 weeks, all-cause mortality and vasospasm-related morbidity occurred in 36.1% (95% CI 30.6%-41.8%) of patients with thick, diffuse SAH and in 14.7% (95% CI 10.8%-19.5%) of those without thick, diffuse SAH. Individual event rates were 7.5% versus 2.5% for all-cause death, 19.4% versus 6.8% for new cerebral infarct, 28.2% versus 9.4% for delayed ischemic neurological deficit, and 24.8% versus 10.8% for rescue therapy due to cerebral vasospasm, respectively. Poor clinical outcome (GOSE score ≥ 4) was observed in 32.7% (95% CI 27.3%-38.3%) and 16.2% (95% CI 12.1%-21.1%) of patients with and without thick, diffuse SAH, respectively. CONCLUSIONS: In a large, centrally adjudicated population of patients with aSAH, WFNS grade at admission and thick, diffuse SAH independently predicted vasospasm-related morbidity and poor 12-week clinical outcome. Patients with thick, diffuse cisternal SAH may be an important cohort to target in future clinical trials of treatment for vasospasm.
Authors: Agnes T Stauning; Frank Eriksson; Goetz Benndorf; Anders V Holst; John Hauerberg; Trine Stavngaard; Lars Poulsgaard; Per Rochat; Vagn Eskesen; Peter Birkeland; Tiit Mathiesen; Tina N Munch Journal: Acta Neurochir (Wien) Date: 2022-07-22 Impact factor: 2.816