Cilostazol and Functional Outcomes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Analysis

Background/Objectives: Poor-grade aneurysmal subarachnoid hemorrhage (SAH; WFNS grades 4–5) carries a historically dismal prognosis, driven by early brain injury and delayed cerebral ischemia (DCI). Despite advances in neurocritical care, effective pharmacological strategies for this vulnerable population remain limited. This multicenter study investigated prognostic factors for functional recovery, with particular emphasis on the potential benefit of adjunctive cilostazol, a phosphodiesterase-3 inhibitor with vasodilatory and antiplatelet properties. Methods: This multicenter retrospective cohort study analyzed 394 patients with WFNS grade 4–5 aneurysmal SAH treated at 10 institutions between 2018 and 2024. The primary outcome was favorable functional status (modified Rankin Scale 0–2) at 6 months. Multivariable logistic regression was performed to identify independent predictors of outcome. Sensitivity analyses were also performed to assess the potential influence of missing 6-month outcome data. Results: Six-month outcomes were available for 318 patients (80.7%), of whom 107 (33.6%) achieved favorable recovery. Patients with favorable outcomes were significantly more likely to have received cilostazol than those with unfavorable outcomes (70.1% vs. 55.5%; p = 0.016). In multivariable logistic regression, cilostazol use remained associated with a favorable outcome (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.01–5.22; p = 0.048) after adjustment for age (OR 0.95; p < 0.001), WFNS grade 5 (OR 0.46; p = 0.012), ventricular drainage, and cerebral infarction. Sensitivity analyses, including propensity score–weighted and missing-outcome analyses, yielded directionally favorable estimates but were not statistically significant. Conclusions: Despite the severity of the initial insult, one-third of patients with available 6-month follow-up achieved functional independence. Cilostazol use was associated with favorable functional outcome in the primary analysis, although statistical significance was not retained in sensitivity analyses addressing missing outcomes. These findings suggest a potential therapeutic signal of cilostazol in poor-grade aneurysmal SAH, warranting prospective validation.

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Journal
Journal of Clinical Medicine
Published
2026-08-18
DOI
https://doi.org/10.3390/jcm15166386
Primary Topic
Intracranial Aneurysms: Treatment and Complications
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article

Cilostazol and Functional Outcomes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Analysis

Fusao Ikawa, Akihiro Hirayama, Yoji Tanaka, Sosho Kajiwara et al.
Journal of Clinical Medicine
Intracranial Aneurysms: Treatment and Complications
article

Cilostazol and Functional Outcomes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Analysis

Fusao Ikawa, Akihiro Hirayama, Yoji Tanaka, Sosho Kajiwara, Yusuke Otsu, Masaki CHIN, Ichiro NAKAHARA, Kiyohiko Sakata, Jin Kikuchi, Kenichiro Suyama, Koreaki Irie, Masaru Hirohata, Katsumi Takizawa, Nobutaka Horie, Hiroki Kurita, Motohiro Morioka, Kimihiko Orito
article en

Abstract

Background/Objectives: Poor-grade aneurysmal subarachnoid hemorrhage (SAH; WFNS grades 4–5) carries a historically dismal prognosis, driven by early brain injury and delayed cerebral ischemia (DCI). Despite advances in neurocritical care, effective pharmacological strategies for this vulnerable population remain limited. This multicenter study investigated prognostic factors for functional recovery, with particular emphasis on the potential benefit of adjunctive cilostazol, a phosphodiesterase-3 inhibitor with vasodilatory and antiplatelet properties. Methods: This multicenter retrospective cohort study analyzed 394 patients with WFNS grade 4–5 aneurysmal SAH treated at 10 institutions between 2018 and 2024. The primary outcome was favorable functional status (modified Rankin Scale 0–2) at 6 months. Multivariable logistic regression was performed to identify independent predictors of outcome. Sensitivity analyses were also performed to assess the potential influence of missing 6-month outcome data. Results: Six-month outcomes were available for 318 patients (80.7%), of whom 107 (33.6%) achieved favorable recovery. Patients with favorable outcomes were significantly more likely to have received cilostazol than those with unfavorable outcomes (70.1% vs. 55.5%; p = 0.016). In multivariable logistic regression, cilostazol use remained associated with a favorable outcome (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.01–5.22; p = 0.048) after adjustment for age (OR 0.95; p < 0.001), WFNS grade 5 (OR 0.46; p = 0.012), ventricular drainage, and cerebral infarction. Sensitivity analyses, including propensity score–weighted and missing-outcome analyses, yielded directionally favorable estimates but were not statistically significant. Conclusions: Despite the severity of the initial insult, one-third of patients with available 6-month follow-up achieved functional independence. Cilostazol use was associated with favorable functional outcome in the primary analysis, although statistical significance was not retained in sensitivity analyses addressing missing outcomes. These findings suggest a potential therapeutic signal of cilostazol in poor-grade aneurysmal SAH, warranting prospective validation.

Journal of Clinical MedicineVol. 15(16)
Kurume University (JP), Hiroshima University (JP), Tokai University (JP), Fujita Health University (JP), Kyorin University (JP), Kurashiki Central Hospital (JP), Fukuoka Hospital (JP), Japanese Red Cross Medical Center (JP), Shimane Prefectural Central Hospital (JP), Japanese Red Cross Asahikawa Hospital (JP), Saitama Medical University (JP)
No poverty
Openalex Percentile: Top 10%
Intracranial Aneurysms: Treatment and Complications
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