Treatment of Acute Cerebral Infarction with Arginine Esterase: A Controlled Study with Heparin

Abstract

Background and Purpose: There is no treatment proven to be of definitive benefit for ischemic stroke. Arginine esterase, a natural product from a snake venom, has been shown to reduce the serum fibrinogen level in human beings and may be useful in the treatment of ischemic stroke. In the present study, we compared the therapeutic effect of arginine esterase with that of heparin. Subjects and Methods: We studied 50 consecutive patients with acute ischemic stroke who were admitted to the Asan Medical Center. We randomly administered either arginine esterase 0.005 unit/kg × 2 times/day or heparin (activated partial thromboplastin time 2–3 times of baseline value) intravenously for 7 days. Antiplatelets were administered afterwards in both groups. Blood fibrinogen, fibrinogen degradation product (FDP) and D-dimer levels were measured at 0, 6, 12, 18 h and 1, 2, 3, 7 and 30 days after the onset of stroke. NIH stroke scale was measured daily by 2 neurologists while Barthel index and Rankin scale were assessed at 7 days and 1 month after the onset of stroke by a research nurse. All these investigators were blinded to the therapeutic regimen each patient received. Results: There were no significant differences in the mean age, gender proportion, stroke subtypes and baseline neurological severity between the two groups. One patient in the arginine esterase group died in an acute stage due to massive herniation and 1 in the heparin group underwent surgery for herniation. One (arginine esterase group) died of massive gastrointestinal bleeding due to previously unrecognized stomach cancer. Otherwise, no significant clinical and laboratory side effects were observed in both groups. In the arginine-esterase treated group, D-dimer and FDP levels were significantly (p < 0.05) elevated, and fibrinogen level significantly (p < 0.05) decreased at 2–7 days after the onset of stroke compared to the heparin-treated group. However, there was no significant difference in the neurological improvement reflected by NIH stroke scale, Barthel index and Rankin scale. Conclusion: Arginine esterase seems to be safe and has significant fibrinolytic effects when administered in the patients with acute ischemic stroke. However, in this preliminary study, it was not superior to heparin in terms of the improvement of neurological deficits. Further studies with larger doses and a larger number of subjects are required.