Table 2.

Beneficial effects of fasudil in human studies

Study	Patient population	Application	Beneficial Effects	Adverse Effects	References
SAH PMS (1995–2000)	1462 patients Age 16–69 years Mean age 54.0 ± 9.9 years	30 mg IV over 30 min 3 times daily 14 days	Preventing cerebral ischemic injury and improving clinical outcome	aMild to moderate in 3.8% patients, similar to phase 3 trial: 3.5% in fasudil vs. 5.7% in placebo group	31
SAH PMS (1995–2000)	3690 patients for fasudil; 1138 patients for fasudil plus ozagrel	30 mg IV over 30 min 3 times daily 14 days	Fasudil plus ozagrel was well tolerated, but did not result in better efficacy than fasudil only	Mild to moderate in 5.2% patients, similar to phase 3 trial: 3.5% in fasudil vs. 5.7% in placebo group	279
SAH Database search meta-analysis (1994–2010)	8 randomized and controlled clinical studies	Variable	Reducing the occurrence of CVS and cerebral infarction (40–50% of the placebo group); improving the clinical outcomes of the patients		282
Acute ischemic stroke Multicenter Phase 3 trial	160 patients age ≥ 20 years mean age 68 years	60 mg IV over 60 min twice daily 14 days	Improving neurological functions and clinical outcome	Mild to moderate, no statistically significant differences in fasudil vs. placebo group	29
Stable angina Multicenter Phase 2 trial	84 patients age 30–80 years	20 to 80 mg PO 3 times daily 8 weeks	Increasing the ischemic threshold of angina patients during exercise and exercise duration	bMild to moderate, 63% in fasudil vs. 53% in placebo group	267
Stable angina Multicenter Phase 2 trial	125 patients age 37–81 years mean age 62 years	5 to 40 mg PO 3 times daily 2–6 weeks	Increasing the maximum exercise time, decreasing the number of anginal attacks	Mild to moderate in <10% patients, including transient headache	266
Stable angina	Study 1: 6 patients age 66.3+/−5 years Study 2: 10 patients age 68.7+/−3.5 years	300 μg/min IC 15 min	Increasing oxygen saturation in coronary sinus vein in study 1; improving pacing-induced myocardial ischemia in study 2		268
Vasospastic angina	20 patients age 49–74 years	300 μg/min IC 15 min	Decreasing ACh-induced coronary constriction, preventing chest pain and ischemic ECG changes		270
Vasospastic angina	26 patients age 61+/−11 years	30 mg, IV following IC 300 μg nitroglycerin	Further dilating ACh-induced coronary spasm in addition to IC nitroglycerin treatment		133
Coronary artery disease	13 patient with confirmed ≥50% stenosis	40 mg, PO 3 times daily 1 month	Improving flow-mediated, endothelium-dependent vasodilation		175
PAH	15 patients age 45+/−4 years	30 mg inhalation over 10 min	Reducing mean PAP and tending to decrease PVR		275
PAH Congenital heart disease	12 pediatric patients age 9.4–16.5 yeras mean age 12.3 years	30 mg/kg IV over 30 min	Decreasing PASP, PVR and SVR, increasing cardiac input and blood oxygen saturation		276
PAH High-altitude	19 patients residents of the Tien-Shan Mountains (altitude 3,200-3,600 m)	1 mg/min IV over 30 min	Increasing pulmonary artery flow, decreasing PASP and PVR	Mild, one patient had facial flushing and four patients had feelings of dryness of the mouth.	274

ACh, acetylcholine; CVS, cerebral vasospasm; IC, intracoronary; IV, intravenous; PAP, pulmonary arterial pressure; PASP, pulmonary artery systolic pressure; PAH, pulmonary arterial hypertension; PMS, post-marketing surveillance; PO, orally; PVR, pulmonary vascular resistance; SAH, subarachnoid hemorrhage; SVR, systemic vascular resistance

^aMild to moderate adverse effects: hemorrhage, cardiovascular system disorders, blood and lymphatic system disorders, hepatic and hepatobiliary disorders, urinary system disorders, hypersensitivity, gastrointestinal system disorders.

^bThe skin and vascular disorders are apparently more frequent in the fasudil group than in the placebo group; skin disorders: allergic dermatitis, benign keratosis, bruise, erythematous rash, hive; vascular disorders: ecchymosis, face flushing, hypotension, hypertension, Raynaud-like phenomenon.