LOW-MOLECULAR-WEIGHT HEPARIN FOR THE TREATMENT OF ACUTE ISCHEMIC STROKE

Background. Despite doubts about their efficacy and concern about thei r safety, antithrombotic agents are often used to treat acute ischemic stroke. Recent experience in patients with other thromboembolic disor ders suggests that low-molecular-weight heparin, which requires only s ubcutaneous administration once or twice daily, may be more effective and safer than standard (unfractionated) heparin. Methods. We conducte d a randomized, double-blind, placebo-controlled trial comparing two d osages of low-molecular-weight heparin with placebo in the treatment o f ischemic stroke. Patients were randomly assigned within 48 hours of the onset of symptoms to receive high-dose nadroparin (4100 anti-facto r Xa IU twice daily), low-dose nadroparin (4100 IU once daily), or pla cebo subcutaneously for 10 days. The primary measure of outcome was de ath or dependency regarding activities of daily living six months afte r randomization. Secondary outcomes were death, hemorrhagic transforma tion of the infarction, and other complications at 10 days, and death of dependency at 3 months. Results. A total of 2750 patients were scre ened for the study. Among 312 patients randomized, 306 had outcomes th at were analyzed at six months. Forty-five patients (45 percent) in th e high-dose group, 53 patients (52 percent) in the low-dose group, and 68 patients (65 percent) in the placebo group died or became dependen t. There was a significant dose-dependent effect among the three study groups in favor of low-molecular-weight heparin (P=0.005 by the chi-s quare test for trend). No significant differences among the groups in the occurrence of secondary outcomes were observed at 10 days. Conclus ions. For patients with ischemic stroke treated within 48 hours of the onset of symptoms, low-molecular-weight heparin was effective in impr oving outcomes at six months.