Principal Findings:

In the acute phase of TIMI 11B, patients randomized to IV unfractionated heparin for at least 3 days or enoxaparin given as a 30 mg IV, followed by subcutaneous injections of 1 mg/kg every 12 hours. Blinding was maintained through a double-dummy placebo design. Double-blind subcutaneous injections were administered for 8 days or until hospital discharge, whichever came first. Overall, median duration of therapy with unfractionated heparin or its matched placebo was 3 days; the median duration of therapy with enoxaparin or its matched placebo was 4.6 days.

Both groups were well-matched at baseline. Approximately 60% of the overall population was diagnosed ultimately as having had unstable angina and 35% with non-Q wave myocardial infarction. Study drug treatment was initiated in 99% of patients.

Kaplan-Meier curves for the composite primary endpoint began to diverge after only 8 hours, showing a 24% relative risk reduction at 48 hours (7.3% vs. 5.5%, p=0.026). At days 8 and 14, the enoxaparin group showed a stable 15% reduction in relative risk, both of which were statistically significant. This risk reduction was achieved without an increase in the rate of either spontaneous or instrumented major hemorrhage.

During the chronic phase of the trial, investigators sought to determine whether any further benefit was achieved with an additional 30 days of enoxaparin therapy following discharge. The initial observed benefit with enoxaparin was sustained through day 43, although no further relative decrease in events was observed. By day 43, the event rate was 17.3% in the enoxaparin group and 19.7% in the unfractionated heparin group, for a relative risk reduction of 12% (p=0.048). There was an increase in the rate of major hemorrhage with chronic enoxaparin therapy compared to placebo (2.9% vs. 1.5%, p=0.02).