ozagrel and Aneurysm--Ruptured

The preventive effect of the serine protease inhibitor FUT-175 (nafamostat mesilate), a potent inhibitor of the complement system, against vasospasm was evaluated in 34 high risk patients with thick and diffuse subarachnoid hemorrhage (SAH) demonstrated by computed tomography corresponding to Fisher group 3. All patients underwent surgery within 96 hours following SAH and received the thromboxane A2 synthetase inhibitor, OKY-046, as part of standard care. FUT-175 (40-160 mg/day) was administered during the initial 4 days following surgery. 455 patients treated without FUT-175 in the Nagasaki SAH Data Bank (non-FUT group) formed the control group. FUT-175 significantly decreased the incidence of symptomatic vasospasm in patients with severe neurological grade (Hunt and Hess grade 3, p < 0.02; Hunt and Hess grade 4, p < 0.02). The incidence of favorable outcome was 76.5% in the FUT group and 60.4% in the non-FUT group, but not statistically different. However, when patients of Hunt and Hess grade 5 were excluded, the FUT group had a significantly improved outcome (p < 0.05). This study suggests that FUT-175 has an additive effect to OKY-046 in preventing vasospasm in high risk patients with severe SAH.

Topics: Aged; Aneurysm, Ruptured; Benzamidines; Brain Damage, Chronic; Brain Ischemia; Drug Evaluation; Drug Synergism; Enzyme Inhibitors; Female; Glasgow Coma Scale; Guanidines; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Methacrylates; Middle Aged; Postoperative Complications; Rupture, Spontaneous; Serine Proteinase Inhibitors; Severity of Illness Index; Subarachnoid Hemorrhage; Thromboxane-A Synthase; Treatment Outcome

Fasudil hydrochloride is a new type of intracellular calcium antagonist, different from the calcium entry blockers that are commonly employed for clinical use. Since September 1995, the combination of fasudil hydrochloride and ozagrel sodium, an inhibitor of thromboxane A2 synthesis, has been used to treat 60 patients at risk of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The effectiveness of this combination therapy was investigated by comparison with the outcome of 57 patients previously treated with only ozagrel sodium. The combination therapy was significantly more effective (p < 0.01) in reducing the incidence of low density areas on computed tomography scans, and reduced, but not significantly, the occurrence of symptomatic vasospasm. The combination therapy of fasudil hydrochloride and ozagrel sodium has superior effectiveness over only ozagrel sodium in treating patients at risk of vasospasm after aneurysmal subarachnoid hemorrhage.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Adult; Aged; Aneurysm, Ruptured; Calcium Channel Blockers; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Methacrylates; Middle Aged; Postoperative Complications; Retrospective Studies; Subarachnoid Hemorrhage; Treatment Outcome