Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older

Objective We sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan. Methods We analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3–6 at discharge) and mortality using multivariable analysis. Results The elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%). Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2–1.7) despite a lower proportion of poor outcomes (0.84, 0.75–0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly. A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17–0.24), statin (0.63, 0.50–0.79), ozagrel sodium (0.72, 0.60–0.86), and cilostazol (0.63, 0.51–0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51–0.68), statin (0.84, 0.75–0.94), and EPA (0.83, 0.72–0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly. Conclusions In contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly.

[1]  Shuntaro Sato,et al.  Impact of perioperative aneurysm rebleeding after subarachnoid hemorrhage. , 2020, Journal of neurosurgery.

[2]  D. Verbaan,et al.  Why do poor grade subarachnoid hemorrhage patients die? , 2019, World neurosurgery.

[3]  H. Urbach,et al.  Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage , 2019, Neurology.

[4]  S. Fukuhara,et al.  Effect of Edaravone on Neurological Symptoms in Real-World Patients With Acute Ischemic Stroke. , 2019, Stroke.

[5]  A. Pace,et al.  A subarachnoid haemorrhage-specific outcome tool , 2018, Brain : a journal of neurology.

[6]  Masato Naraoka,et al.  Aneurysmal Subarachnoid Hemorrhage in the Elderly over Age 75: A Systematic Review , 2017, Neurologia medico-chirurgica.

[7]  C. Oppenheim,et al.  Treatment of cerebral vasospasm following aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis , 2017, European Radiology.

[8]  B. Lapin,et al.  Added Value of Patient‐Reported Outcome Measures in Stroke Clinical Practice , 2017, Journal of the American Heart Association.

[9]  S. Matsuda,et al.  Effect of treatment modality on in-hospital outcome in patients with subarachnoid hemorrhage: a nationwide study in Japan (J-ASPECT Study). , 2017, Journal of neurosurgery.

[10]  Koshi Nakamura,et al.  Diagnosis Procedure Combination Database Would Develop Nationwide Clinical Research in Japan. , 2016, Circulation journal : official journal of the Japanese Circulation Society.

[11]  Alison Clarke,et al.  The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT) , 2015, The Lancet.

[12]  S. Matsuda,et al.  The impact of comprehensive stroke care capacity on the hospital volume of stroke interventions: a nationwide study in Japan: J-ASPECT study. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[13]  J. Makino,et al.  End-of-life considerations in the ICU in Japan: ethical and legal perspectives , 2014, Journal of Intensive Care.

[14]  K. Ogasawara,et al.  A prospective, multicenter, randomized study of the efficacy of eicosapentaenoic acid for cerebral vasospasm: the EVAS study. , 2014, World neurosurgery.

[15]  D. Kallmes,et al.  Comparative Effectiveness of Ruptured Cerebral Aneurysm Therapies: Propensity Score Analysis of Clipping versus Coiling , 2014, American Journal of Neuroradiology.

[16]  M. Murad,et al.  Endovascular Treatment of Intracranial Aneurysms in Elderly Patients: A Systematic Review and Meta-Analysis , 2013, Stroke.

[17]  Yoshiyuki Watanabe,et al.  The eye response test alone is sufficient to predict stroke outcome—reintroduction of Japan Coma Scale: a cohort study , 2013, BMJ Open.

[18]  D. Kallmes,et al.  Comparative Effectiveness of Unruptured Cerebral Aneurysm Therapies: Propensity Score Analysis of Clipping Versus Coiling , 2013, Stroke.

[19]  E. Connolly,et al.  Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2012, Stroke.

[20]  Satoshi Suzuki,et al.  Cilostazol Improves Outcome after Subarachnoid Hemorrhage: A Preliminary Report , 2011, Cerebrovascular Diseases.

[21]  Michiyasu Suzuki,et al.  A proposed definition of symptomatic vasospasm based on treatment of cerebral vasospasm after subarachnoid hemorrhage in Japan: Consensus 2009, a project of the 25th Spasm Symposium , 2011, Surgical neurology international.

[22]  R. Macdonald,et al.  Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  P. Austin,et al.  The impact of therapeutic modality on outcomes following repair of ruptured intracranial aneurysms: an administrative data analysis. Clinical article. , 2010, Journal of neurosurgery.

[24]  J. Benichou,et al.  Interdisciplinary treatment of ruptured cerebral aneurysms in elderly patients. , 2010, Journal of neurosurgery.

[25]  T. van der Poll,et al.  Biologic Effects of Simvastatin in Patients with Aneurysmal Subarachnoid Hemorrhage: A Double-Blind, Placebo-Controlled Randomized Trial , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  Masato Naraoka,et al.  EFFECT OF A FREE RADICAL SCAVENGER, EDARAVONE, IN THE TREATMENT OF PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE , 2009, Neurosurgery.

[27]  Per Enblad,et al.  International Subarachnoid Aneurysm Trial of Neurosurgical Clipping Versus Endovascular Coiling: Subgroup Analysis of 278 Elderly Patients , 2008, Stroke.

[28]  V. Feigin,et al.  Calcium Antagonists for Aneurysmal Subarachnoid Hemorrhage , 2008 .

[29]  John A. Cowan,et al.  Use of endovascular coil embolization and surgical clip occlusion for cerebral artery aneurysms. , 2007, Journal of neurosurgery.

[30]  K. Takakura,et al.  A postmarketing surveillance study of fasudil treatment after aneurysmal subarachnoid hemorrhage. , 2007, Surgical neurology.

[31]  J. Pickard,et al.  Effects of Acute Pravastatin Treatment on Intensity of Rescue Therapy, Length of Inpatient Stay, and 6-Month Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage , 2007, Stroke.

[32]  R. Macdonald,et al.  PREDICTORS OF CEREBRAL INFARCTION IN PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE , 2007, Neurosurgery.

[33]  Kazuhiko Ohe,et al.  Impact of the Japanese Diagnosis Procedure Combination-based Payment System on cardiovascular medicine-related costs. , 2005, International heart journal.

[34]  A. Molyneux.  International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial , 2002, The Lancet.

[35]  C. Anderson,et al.  Health outcomes 1 year after subarachnoid hemorrhage , 2000, Neurology.

[36]  L. Beenen,et al.  Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in The Netherlands , 2000, Journal of neurology, neurosurgery, and psychiatry.

[37]  C. Ogilvy,et al.  Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis. , 1996, Journal of neurosurgery.

[38]  K. Takakura,et al.  Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. , 1992, Journal of neurosurgery.

[39]  T. Ohnishi,et al.  Efficacy and toxicity of thromboxane synthetase inhibitor for cerebral vasospasm after subarachnoid hemorrhage. , 1991, Surgical neurology.

[40]  Brinkman Gl,et al.  The effect of bronchitis, smoking, and occupation on ventilation. , 1963 .

[41]  V. Seifert,et al.  Outcome after Hunt and Hess Grade V subarachnoid hemorrhage: a comparison of pre-coiling era (1980-1995) versus post-ISAT era (2005-2014). , 2018, Journal of neurosurgery.

[42]  Michael T. Lawton,et al.  SUBARACHNOID HEMORRHAGE , 2017, The New England journal of medicine.

[43]  H. Kinouchi,et al.  Effects of cilostazol on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a multicenter prospective, randomized, open-label blinded end point trial. , 2013, Journal of neurosurgery.

[44]  棟方 聡.  Effect of a free radical scavenger, edaravone in the treatment of patients with aneurysmal subarachnoid hemorrhage , 2009 .

[45]  C. Mottolese,et al.  Level of consciousness and age as prognostic factors in aneurysmal SAH , 2005, Acta Neurochirurgica.

[46]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.

[47]  E. O. Coates,et al.  The effect of bronchitis, smoking, and occupation on ventilation. , 1963, The American review of respiratory disease.

[48]  Y. V. van Maercke,et al.  [Subarachnoid hemorrhage]. , 1961, Belgisch tijdschrift voor geneeskunde.

[49]  Peter Sandercock,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .