Effects of intravenous human albumin, enteral cilostazol, and combination therapy on the reduction of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND

Delayed cerebral ischemia (DCI) and cerebral infarction remain major causes of disability and death after aneurysmal subarachnoid hemorrhage (aSAH). Enteral cilostazol and intravenous (IV) 25% human albumin have each been investigated as candidate therapies targeting potentially overlapping DCI mechanisms.

OBJECTIVE

This article aims to estimate the plausible effects of albumin, cilostazol, and combination therapy on reducing DCI after aSAH using Bayesian prior-predictive simulation and factorial component-effect decomposition.

METHODS

We defined four treatment classes: control, albumin-only, cilostazol-only, and combination therapy. The primary endpoint was the National Institute of Neurological Disorders and Stroke Common Data Elements-defined DCI (CDE-d-DCI) on computed tomography on days 10 to 14. A prior-predictive Monte Carlo model used a control DCI-risk prior centered on the Cilostazol Albumin Treatment in Subarachnoid Hemorrhage (CATS) protocol-planning value of 31%, a cilostazol prior anchored to randomized-trial meta-analysis estimates, and an albumin prior informed by the Albumin in Subarachnoid Hemorrhage (ALISAH) dose-escalation data with wider uncertainty because ALISAH was uncontrolled. No observed CATS outcomes were analyzed. External consistency, control-prior sensitivity, weaker albumin priors, correlated-prior structures, and factorial component effects were evaluated.

RESULTS

Under base-case priors, median absolute risk reductions (ARRs) versus control were 9.1 percentage points for albumin (90% simulation interval, -3.3 to 18.1; prior-predictive probability of ARR > 0, 89.8%), 18.1 percentage points for cilostazol (11.0 to 25.4; 99.9%), and 21.7 percentage points for combination therapy (12.4 to 29.9; 99.8%). Although combination therapy had the largest projected reduction versus control, the incremental benefit of adding albumin to cilostazol was small and uncertain (3.5 percentage points; -3.0 to 8.9), and the additive interaction was also uncertain (-5.5 percentage points; -11.9 to 2.8). Illustrative two-group sample sizes were 343, 76, and 49 participants per group for albumin, cilostazol, and combination therapy, respectively, versus control.

CONCLUSION

These simulations provide planning-level projections and do not establish efficacy. The findings support continued randomized evaluation of cilostazol and albumin, with concurrent single-agent, combination, and control arms to estimate component effects and interaction effects.