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.