Improving outcomes in acute coronary syndromes - The FRISC II trial

The FRISC II study addressed two key questions in the management of acute coronary syndromes: is it beneficial to extend low-molecular-weight heparin (LMWH) therapy with dalteparin beyond the initial period of acute treatment; and, is a strategy of early invasive therapy, including angioplasty and surgical revascularization, preferable to a more conservative strategy? The study focused on patients with unstable coronary artery disease (UCAD), that is, angina and non-ST-segment-elevation myocardial infarction (MI). Patients were allocated in a randomized, factorial study design to either an invasive or a conservative management strategy. Within each of these groups, patients were further randomized to receive either 3 months of extended treatment with dalteparin or placebo, following at least 5 days' treatment with open-label dalteparin. After 1 year, patient survival and MI-free survival were significantly higher in the invasive therapy group than in the noninvasive group. Patients who received extended dalteparin treatment had a significantly reduced probability of death or MI after 1 month (relative risk reduction 47%; p = 0.002), a benefit still evident after 60 days, but after 3 months there was no longer any significant clinical advantage compared with placebo. There was, however, a significant reduction in the combined incidence of death, MI, or revascularization at 3 months in the extended dalteparin treatment group (relative risk reduction 13%; p = 0.031). The benefits of extended dalteparin treatment were particularly marked in patients with elevated troponin-Tr or ST-segment depression. A subgroup analysis of conservatively managed patients who underwent revascularization in the first 45 days revealed that the probability of death or MI at 1 year was significantly lower among patients who received extended dalteparin treatment (relative risk reduction 35%; p = 0.02). Extended dalteparin treatment Is, however, associated with a small increase in bleeding risk. In conclusion, early invasive therapy (following combined treatment with aspirin and dalteparin) is recommended in a majority of patients with UCAD. Furthermore, extended dalteparin treatment for up to 45 days is efficacious and well tolerated, and therefore provides a useful "bridge'' to revascularization when early revascularization is not immediately available.