Prognosis of patients with aneurysmal subarachnoid hemorrhage treated with fasudil hydrochloride–cilostazol combination therapy: A cross-sectional analysis of a nationwide inpatient database, 2016 to 2020

Fasudil hydrochloride is used as a therapeutic agent for cerebral vasospasm after aneurysmal subarachnoid hemorrhage surgery; however, its limited efficacy necessitates additional treatment options. Although the therapeutic potential of cilostazol for improved outcomes after aneurysmal subarachnoid hemorrhage has been reported, no clinical studies have examined the effects of administering both cilostazol and fasudil hydrochloride on mortality and physical disability in patients. Therefore, we investigated the impact of combined fasudil hydrochloride and cilostazol administration among patients with subarachnoid hemorrhage (SAH) in Japan. A cross-sectional study was conducted using the diagnosis procedure combination database among patients with SAH who received fasudil hydrocholoride alone (n = 8728) or in combination with cilostazol (n = 8052) between April 2016 and March 2020. The primary endpoint was in-hospital mortality, and the secondary endpoint was the proportion of patients with a modified Rankin Scale (mRS) score ≤2 at discharge. Statistical analysis was performed using multivariate-adjusted logistic regression analysis with a significance level of 5%. The mean age was 63.8 years (standard deviation [SD]: 14.4) in the fasudil hydrochloride monotherapy group (F group) and 62.8 years (SD: 14.3) in the fasudil hydrochloride and cilostazol combination group (FC group). Female patients accounted for 69.5% in the F group and 70.1% in the FC group. The in-hospital mortality rate was 7.4% in the F group and 4.0% in the FC group. Patients in the FC group had a lower in-hospital mortality rate than did those in the F group (odds ratio 0.28, 95% confidence interval [CI] 0.23-0.34, P < .001). The proportion of patients with an mRS score ≤2 at discharge was 49.4% in the F group and 55.7% in the FC group. Patients in the FC group had a higher mRS score ≤2 at discharge than those in the F group (odds ratio 1.43, 95% CI: 1.31-1.55, P < .001). We investigated the impact of combined fasudil hydrochloride and cilostazol administration on the prognosis of Japanese patients with SAH. The results suggest that combination therapy with fasudil hydrochloride and cilostazol may have a synergistic effectiveness on improving SAH prognosis compared with fasudil hydrochloride monotherapy. In future, research is needed to understand the mechanisms underlying the combined use of cilostazol.