Low-molecular-weight heparin and early neurologic deterioration in acute stroke caused by large artery occlusive disease

Arch Neurol. 2012 Nov;69(11):1454-60. doi: 10.1001/archneurol.2012.1633.


Background: Patients with acute ischemic stroke and large artery occlusive disease (LAOD) have an increased risk for early neurologic deterioration (END) due to progressive stroke, early recurrent ischemic stroke(ERIS), or symptomatic intracranial cerebral hemorrhage(SICH). Low-molecular-weight heparin (LMWH)has been widely advocated to prevent venous thromboembolism,but its risks and benefits in early ischemic stroke are inadequately defined.

Objective: To determine the efficacy and safety of LMWH in treating END in patients with acute ischemic stroke and LAOD.

Design: Post hoc analysis of randomized, controlled trial.

Setting: Academic research.

Patients: Among 603 patients recruited, 353 patients(180 treated with LMWH, 173 with aspirin) had acute ischemic stroke and LAOD.

Interventions: Patients were randomly assigned to receive either subcutaneous LMWH or oral aspirin within 48 hours after stroke onset for 10 days, then all received aspirin once daily for 6 months.

Main outcome measures: We assessed whether LMWH was superior to aspirin for the prevention of END within the first 10 days after index stroke. Early neurologic deterioration was defined as a composite end point of progressive stroke, ERIS, and SICH.

Results: Among 353 patients included in the study, END within the first 10 days occurred in 6.7% of LMWH allocated patients (12 of 180 patients) compared with 13.9% of aspirin-allocated patients (24 of 173). Low molecular-weight heparin was significantly associated with the reduction of END(absolute risk reduction, 7.2%; odds ratio [OR], 0.44; 95% CI, 0.21-0.92). When individual components of END were examined, LMWH was significantly associated with a lower frequency of stroke progression within the first 10 days compared with aspirin(5.0% [9 of 180] vs 12.7% [22 of 173]; OR, 0.36; 95%CI, 0.16-0.81). Meanwhile, among those taking LMWH vs aspirin, the frequency rates of ERIS were 1.1% (2 of 180) vs 0 (0); 0.6% (1 of 180) vs 1.2% (2 of 173) for SICH;and 2.2% (4 of 180) vs 2.9% (5 of 173) for symptomatic and asymptomatic cerebral hemorrhage, respectively; they showed nonsignificant trends. Early neurologic deterioration was significantly associated with 6-month disability with both LMWH(OR, 12.75; 95% CI, 3.27-49.79 on Barthel Index and OR, 18.15; 95% CI, 2.09-157.93 on modified Rankin Scale) and aspirin (OR, 6.09; 95% CI,2.44-15.20 on Barthel Index and OR, 7.50; 95% CI, 2.08-27.04 on modified Rankin Scale) groups.

Conclusions: For patients with acute ischemic stroke and LAOD, treatment with LMWH within 48 hours of stroke may reduce END during the first 10 days, mainly by preventing stroke progression. The similar rate of cerebral hemorrhage between LMWH and aspirin demonstrated that LMWH may be safely used in acute ischemic stroke.

Trial registration: stroke center.org/trials Identifier: FISS -tris

Publication types

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

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Arterial Occlusive Diseases / complications
  • Aspirin / administration & dosage
  • Chi-Square Distribution
  • Drug Administration Routes
  • Female
  • Follow-Up Studies
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / etiology*
  • Severity of Illness Index
  • Stroke / complications*
  • Stroke / etiology
  • Time Factors
  • Treatment Outcome


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Aspirin