Low-molecular-weight heparin for the treatment of acute ischemic stroke

N Engl J Med. 1995 Dec 14;333(24):1588-93. doi: 10.1056/NEJM199512143332402.


Background: Despite doubts about their efficacy and concern about their safety, antithrombotic agents are often used to treat acute ischemic stroke. Recent experience in patients with other thromboembolic disorders suggests that low-molecular-weight heparin, which requires only subcutaneous administration once or twice daily, may be more effective and safer than standard (unfractionated) heparin.

Methods: We conducted a randomized, double-blind, placebo-controlled trial comparing two dosages of low-molecular-weight heparin with placebo in the treatment of ischemic stroke. Patients were randomly assigned within 48 hours of the onset of symptoms to receive high-dose nadroparin (4100 anti-factor Xa IU twice daily), low-dose nadroparin (4100 IU once daily), or placebo subcutaneously for 10 days. The primary measure of outcome was death or dependency regarding activities of daily living six months after randomization. Secondary outcomes were death, hemorrhagic transformation of the infarction, and other complications at 10 days, and death or dependency at 3 months.

Results: A total of 2750 patients were screened for the study. Among 312 patients randomized, 306 had outcomes that were analyzed at six months. Forty-five patients (45 percent) in the high-dose group, 53 patients (52 percent) in the low-dose group, and 68 patients (65 percent) in the placebo group died or became dependent. 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-square test for trend). No significant differences among the groups in the occurrence of secondary outcomes were observed at 10 days.

Conclusions: For patients with ischemic stroke treated within 48 hours of the onset of symptoms, low-molecular-weight heparin was effective in improving outcomes at six months.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Acute Disease
  • Aged
  • Brain Ischemia / drug therapy
  • Cerebral Hemorrhage / etiology
  • Cerebral Infarction / drug therapy
  • Cerebrovascular Disorders / complications
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / mortality
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Logistic Models
  • Male
  • Nadroparin / administration & dosage*
  • Nadroparin / adverse effects
  • Treatment Outcome


  • Nadroparin