Durham, NC - Long-term results of the SYNERGY trial have shown similar rates of death/MI at six months in ACS patients treated with enoxaparin and those given unfractionated heparin (UFH) for their initial hospital treatment. The results, published in the November 23, 2005 issue of the Journal of the American Medical Association, also show no difference in one-year mortality rates between the two groups.

One alarming observation from the latest set of results from this trial, however, is the high rate of death/MI in the overall population at six months—almost 18%. Lead author Dr Kenneth Mahaffey (Duke Clinical Research Institute, Durham, NC) commented to heartwire that despite the very high rates of revascularization and optimal medical therapy, these patients are still at very high risk of recurrent events. "In the highest-risk patients in this trial—those over 60, with a positive biomarker and ECG changes (who made up 45% of the patients enrolled)—one in five had either died or had a recurrent MI by six months. That is unbelievable and is a worse outcome than that associated with a lot of cancers. It shows that we have much more work to do."

In the SYNERGY trial, 9978 ACS patients at high risk for recurrent ischemic cardiac events treated with an early invasive management strategy were randomly assigned to receive enoxaparin or unfractionated heparin. The primary end point of death/MI at 30 days, reported previously, was similar between the two groups, but there was more bleeding with enoxaparin.

One of the major observations from the 30-day results was that patients tended to do worse if their antithrombin therapy was switched at any time before or after randomization. And in a subgroup analysis of just those patients receiving consistent treatment, there was a reduction in death/MI at 30 days with enoxaparin. This benefit was still present at six months. But there was no difference in one-year mortality rates between groups, even in those given consistent treatment.

Mahaffey said the SYNERGY investigators were not surprised by the long-term results. He said it was reassuring to see that the benefit of consistent treatment with enoxaparin was still present at six months and that he was not disappointed that the one-year mortality in this subgroup was not reduced. "We did not collect MI data at one year and so we only have mortality data at this point," he explained, adding. "Many previous trials that have shown reductions in early MI rates have not shown reductions in one-year mortality, so we did not anticipate differences in one-year mortality in this trial."

He commented that the consistent-therapy subgroup analysis was "an intriguing result," which, when combined with the totality of the data from a meta-analysis of trials comparing enoxaparin with unfractionated heparin in ACS, suggested better outcomes with the low-molecular-weight heparin. However, some other experts in the field have questioned the applicability of the meta-analysis to modern-day practice as it includes several outdated trials. This was the crux of a lively debate between Drs Robert Califf (Duke Clinical Research Institute, Durham, NC) and Steve Nissen (Cleveland Clinic, OH) at last week's AHA meeting.

Mahaffey pointed out to heartwire that further data on this issue would be forthcoming from the RESCUE trial, which is comparing enoxaparin with unfractionated heparin in patients not already on an antithrombin when enrolled. These patients will therefore be similar to the consistent-therapy subgroup in SYNERGY. The results of RESCUE will be available early next year.