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

Abstract

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.