The study's primary end point was the incidence of death or MI by 30 days after initial treatment, which occurred in 9.7% of patients treated with fondaparinux and in 11.2% of those treated with placebo or heparin, a 14% relative difference that was statistically significant. The results were published online concurrent with the report at the meeting (JAMA 2006 Mar. 14 [Epub doi:10.1001/jama.295.13.joc60038]).
The rate of major bleeds during the first 9 days of treatment was 1.8% in patients treated with fondaparinux and 2.1% in the control patients, a difference that was not significantly different.
The analysis also included a net clinical benefit calculation that totaled the rate of death, MI, stroke, and severe hemorrhage by the end of the study. This rate was reduced by 12% in the fondaparinux group, compared with the control patients, a significant difference. For every 1,000 patients treated, fondaparinux prevented 16 episodes of death, MI, strokes, and severe bleeds, compared with placebo or heparin, Dr. Yusuf reported.
Fondaparinux is a synthetic inhibitor of factor Xa, an early step in the coagulation cascade, and uses a different mechanism than do unfractionated heparin and the low-molecular-weight heparins, which block other coagulation factors. This difference in activity seems to be linked to the reduced hemorrhage risk posed by fondaparinux, and use of the drug may have resulted in fewer deaths because bleeding was reduced.
“We believe that when a patient has a bleeding event, it leads to worse long-term outcomes, including increased long-term mortality,” said Dr. Christopher B. Granger, a coinvestigator of OASIS-6 and cardiac care unit director at Duke University.