Thick and diffuse cisternal clot independently predicts vasospasm-related morbidity and poor outcome after aneurysmal subarachnoid hemorrhage

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  • 1 Department of Neurosurgery, University of Maryland, Baltimore, Maryland;
  • 2 Department of Neurointerventional Radiology, University of California San Francisco Medical Center, San Francisco, California;
  • 3 Global Clinical Development, Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland;
  • 4 Department of Neurological Surgery, University of California San Francisco, Fresno, California;
  • 5 Department of Surgery, University of Toronto, Ontario, Canada;
  • 6 Department of Neurology, Henry Ford Neuroscience Institute, Wayne State School of Medicine, Detroit, Michigan; and
  • 7 Department of Anesthesia and Critical Care, Hôpital de la Timone, Aix-Marseille Université, Marseille, France
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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.

ABBREVIATIONS aSAH = aneurysmal SAH; BNI = Barrow Neurological Institute; CONSCIOUS = Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage; DCI = delayed cerebral ischemia; DIND = delayed ischemic neurological deficit; GOSE = Glasgow Outcome Scale–Extended; IVH = intraventricular hemorrhage; SAH = subarachnoid hemorrhage; WFNS = World Federation of Neurosurgical Societies.

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Contributor Notes

Correspondence E. François Aldrich: University of Maryland, Baltimore, MD. caldrich12@comcast.net.

INCLUDE WHEN CITING Published online May 22, 2020; DOI: 10.3171/2020.3.JNS193400.

Disclosures Drs. Aldrich, Higashida, Mayer, and Bruder have been consultants/scientific advisors for Idorsia Pharmaceuticals Ltd. and have received consulting fees. Mr. Hmissi, Ms. Marr, and Dr. Roux are employees of Idorsia Pharmaceuticals Ltd. (formerly Actelion Pharmaceuticals Ltd.), which is the owner and developer of clazosentan.

The CONSCIOUS-2 and CONSCIOUS-3 studies were funded by Actelion Pharmaceuticals Ltd. The sponsorship of these studies was transferred to Idorsia Pharmaceuticals Ltd. on July 1, 2018.

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