Low-molecular-weight heparin (Fragmin) during instability in coronary artery disease (FRISC). FRISC Study Group.

This study evaluated whether the low-molecular-weight (LMW) heparin dalteparin sodium (Fragmin) had protective effects against cardiac events in aspirin-treated patients with unstable coronary artery syndromes. Patients (n = 1,506) with unstable angina or non-Q-wave myocardial infarction were randomized to double-blind, placebo-controlled treatment with LMW heparin. The treatment was given as subcutaneous injections: 120 U/kg body weight/12 hours during the first 5-7 days and 7,500 U once daily during the following 35-45 days. The primary endpoint, death or myocardial infarction after 6 days, showed a 3% (4.7%-1.7%) absolute and a 65% relative reduction in the LMW heparin group. There was a 6.8% (15.5%-8.7%) absolute and a 47% relative reduction of urgent revascularization or need for heparin or nitroglycerin infusions in combination with the primary endpoint. After 40 days there was an absolute reduction of death or myocardial infarction of 2.8% (10.7%-7.9%) and its combination with incapacitating angina was reduced by 5.9% (30.7%-24.8%). The survival analysis indicated a reactivation of the instability soon after lowering the dose at 5-7 days. With long-term follow-up, 3-4 months after termination of LMW heparin, the differences between groups were no longer statistically significant. However, the cumulative reduction in death, myocardial infarction, and revascularization because of incapacitating angina of 5.1% (25.3%-20.4%) was maintained. No cerebral and few major bleeds occurred. Compliance was adequate. Thus, subcutaneous LMW heparin protects against cardiac events in the acute phase of unstable coronary artery disease. The subcutaneous regimen also allows prolongation of treatment in the outpatient setting, which might maintain the initial benefits over a longer period.