Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid Hemorrhage-Results of a Randomized Trial of Fasudil Hydrochloride Versus Nimodipine-

Abstract

The efficacy and safety of fasudil hydrochloride, a novel protein kinase inhibitor, were evaluated for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms in patients with ruptured cerebral aneurysm. This randomized open trial with nimodipine as the control included 72 patients who underwent subarachnoid hemorrhage surgery for ruptured cerebral aneurysm of Hunt and Hess grades I to IV. For 14 days following surgery, patients were administered either 30 mg of fasudil hydrochloride by intravenous injection over a period of 30 minutes three times a day or 1 mg/hr of nimodipine by continuous intravenous infusion. Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine. Adverse reactions occurred in 13 of 37 patients receiving fasudil hydrochloride and 15 of 35 patients receiving nimodipine. There were no serious adverse events in the fasudil group. The results of this clinical trial indicate that fasudil hydrochloride is a safe and efficient agent for suppressing cerebral vasospasm after subarachnoid hemorrhage surgery for ruptured cerebral aneurysm.

Safety and Efficacy of Fasudil Monotherapy and Fasudil-Ozagrel Combination Therapy in Patients With Subarachnoid Hemorrhage: Sub-analysis of the Post-marketing Surveillance Study

“…20) Fasudil is widely used in patients with SAH in Japan. A randomized trial in the People's Republic of China described the safety and efficacy of fasudil for suppressing cerebral vasospasm after SAH, 24) and fasudil is used in patients undergoing surgery for SAH.…”

Preventing Vasospasm Improves Outcome After Aneurysmal Subarachnoid Hemorrhage: Rationale and Design of CONSCIOUS-2 and CONSCIOUS-3 Trials

“…Current management options for the prevention and treatment of vasospasm and DIND include hemodynamic therapy, nimodipine, fasudil (in Japan), intra-arterial vasodilators and angioplasty, but none are very effective [7][8][9][10][11][12]. Clazosentan is an endothelin receptor antagonist under investigation for the prevention of vasospasm and subsequent morbidity and mortality.…”

“…Angiographic vasospasm (vasospasm that is visible on an angiogram) occurs in up to 70% of patients after aSAH [6]; DIND has been estimated to account for 50% of deaths in people surviving the initial SAH [7]. Current management options for the prevention and treatment of vasospasm and DIND include hemodynamic therapy, nimodipine, fasudil (in Japan), intra-arterial vasodilators and angioplasty, but none are very effective [7][8][9][10][11][12]. Clazosentan is an endothelin receptor antagonist under investigation for the prevention of vasospasm and subsequent morbidity and mortality.…”

Efficacy and Safety of Fasudil in Patients With Subarachnoid Hemorrhage: Final Results of a Randomized Trial of Fasudil Versus Nimodipine

“…19,20) Interim results of a randomized trial of fasudil versus nimodipine have shown that fasudil is at least equally potent compared with nimodipine for the prevention of cerebral vasospasm and subsequent ischemic injury in patients undergoing surgery for SAH in the People's Republic of China. 23) Here we report the final results of this trial to evaluate the efficacy and safety of fasudil.…”