Treatment of acute cerebral infarction with arginine esterase: A controlled study with heparin

Background and Purpose: There is no treatment proven to be of definitive be nefit for ischemic stroke. Arginine esterase, a natural product from a snak e venom, has been shown to reduce the serum fibrinogen level in human being s and may be useful in the treatment of ischemic stroke. In the present stu dy, we compared the therapeutic effect of arginine esterase with that of he parin. Subjects and Methods: We studied 50 consecutive patients with acute ischemic stroke who were admitted to the Asan Medical Center. We randomly a dministered either arginine esterase 0.005 unit/kg x 2 times/day or heparin (activated partial thromboplastin time 2-3 times of baseline value) intrav enously for 7 days. Antiplatelets were administered afterwards in both grou ps. Blood fibrinogen, fibrinogen degradation product (FDP) and D-dimer leve ls were measured at 0, 6, 12, 18 h and 1, 2, 3, 7 and 30 days after the ons et of stroke. NIH stroke scale was measured daily by 2 neurologists while B arthel 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 si gnificant differences in the mean age, gender proportion, stroke subtypes a nd baseline neurological severity between the two groups. One patient in th e 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 un recognized stomach cancer. Otherwise, no significant clinical and labor atory side effects were observed in both groups. In the arginine-esterase t reated 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 este rase seems to be safe and has significant fibrinolytic effects when adminis tered in the patients with acute ischemic stroke. However, in this prelimin ary study, it was not superior to heparin in terms of the improvement of ne urological deficits. Further studies with larger doses and a larger number of subjects are required. Copyright (C) 2001 S.Karger AG, Basel.