Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease. Investigators

Lancet. 1999 Aug 28;354(9180):701-7.


Background: Short-term treatment with subcutaneous low-molecular-mass heparin in addition to aspirin is effective in unstable coronary-artery disease. We assessed the efficacy of long-term treatment with dalteparin in patients managed with a non-invasive treatment strategy.

Methods: 2267 patients from three Scandinavian countries (median age 67 years, 68% men) with unstable coronary-artery disease were randomly assigned to continue double-blind subcutaneous dalteparin twice daily or placebo for 3 months, after at least 5 days' treatment with open-label dalteparin. The composite primary endpoint was death or myocardial infarction. Analysis was by intention to treat.

Findings: During the 3 months of double-blind treatment, there was a non-significant decrease in the composite endpoint of death or myocardial infarction of 6.7% and 8.0% in the dalteparin and placebo groups, respectively (risk ratio 0.81 [95% CI 0.60-1.10], p=0.17). At 30 days, this decrease was significant (3.1 vs 5.9%, 0.53 [0.35-0.80]; p=0.002). In the total cohort there was at 3 months a decrease in death, myocardial infarction, or revascularisation (29.1 vs 33.4%, 0.87 [0.77-0.99]; p=0.031). The initial benefits were not sustained at 6-month follow-up.

Interpretation: Long-term dalteparin lowers the risk of death, myocardial infarction, and revascularisation in unstable coronary-artery disease at least during the first month of therapy. These early protective effects could be used to lower the risk of events in patients waiting for invasive procedures.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angina, Unstable / drug therapy*
  • Angina, Unstable / mortality
  • Cohort Studies
  • Dalteparin / administration & dosage*
  • Dalteparin / adverse effects
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Subcutaneous
  • Long-Term Care
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / mortality
  • Myocardial Revascularization / statistics & numerical data
  • Prospective Studies
  • Scandinavian and Nordic Countries
  • Survival Rate


  • Dalteparin