Sildenafil treatment of subacute ischemic stroke: a safety study at 25-mg daily for 2 weeks.
BACKGROUND
In several animal studies of young and aged rats with ischemic stroke, treatment with sildenafil improved functional outcomes compared with placebo. We conducted a safety study of sildenafil (25 mg daily for 2 weeks) shortly after ischemic stroke onset.


METHODS
We recruited patients aged 18 to 80 years with ischemic stroke, National Institutes of Health stroke scale (NIHSS) score 2 to 21, between days 2 and 9 after symptom onset. Patients were treated with sildenafil for 2 weeks (25 mg daily). The primary outcome measure was the adverse occurrence of any of the following during the treatment period: stroke worsening, new stroke, myocardial infarction, vision loss, hearing loss, or death from any cause. Secondary outcome measures were NIHSS score, Barthel indices, and modified Rankin score at 90 days.


RESULTS
Twelve patients were recruited. Mean age was 57 years, 5 were female, and median NIHSS score at entry was 9.5 (range 2-20). The primary outcome measure occurred in one patient (sudden death). Another patient committed suicide 2 months after study entry (and 6 weeks after treatment with sildenafil had been completed). Among the 10 survivors, at 90 days, median NIHSS score was 2 (range 0-12), median Barthel index was 95 (range 15-100), and median modified Rankin score was 1.5 (range 0-5).


CONCLUSIONS
Sildenafil (25 mg daily for 2 weeks) appeared to be safe in this group of patients with mild to moderately severe stroke. Further studies of higher doses will be tested.
Silver
Brian
B
Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA. bsilver1@hfhs.org
McCarthy
Sharon
S
Lu
Mei
M
Mitsias
Panayiotis
P
Russman
Andrew N
AN
Katramados
Angelos
A
Morris
Daniel C
DC
Lewandowski
Christopher A
CA
Chopp
Michael
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000517:prevention & control; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011655:Pulmonary Embolism / Q000139:chemically induced; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D000068677:Sildenafil Citrate; D020521:Stroke / Q000188:drug therapy* / Q000517:prevention & control; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D020246:Venous Thrombosis / Q000139:chemically induced; D055815:Young Adult
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D006152:Cyclic GMP