Drug Eluting Stents Linked to Increased Mortality in Saphenous Vein Grafts

ANTWERP, Belgium, July 10 -- A long term follow-up of saphenous vein grafts revealed increased mortality for patients treated with sirolimus-eluting (Cypher) stents than for those given bare-metal devices.
At a median of 32 months, there were there 11 deaths among 38 patients treated with the drug-eluting stents and no deaths among 37 who received bare-metal devices, an absolute difference of 29% (P <0.001), wrote Paul Vermeersch, M.D., of the Antwerp Cardiovascular Institute Middleheim, and colleagues.
These data emerged in the secondary post hoc analysis of DELAYED RRISC (Death and Events at Long-Term follow-up AnalYssi: Extended Duration of the Reduction In Saphenous vein graft with Cypher) trial, the investigators reported in the July 17 issue of the Journal of the American College of Cardiology.
Dr. Vermeersch and colleagues previously reported that compared with bare-metal stents, Cypher significantly reduced six-month restenosis and revascularization rates in this population. But "the benefit of [sirolimus-eluting stents] in terms of reduced revascularization procedures shown at six months was no longer evident up to three years," they wrote.
All patients were treated from September 2003 to November 2004. The median follow-up was 30.5 months for both treatment groups. The 75 patients had a total of 96 lesions in 80 saphenous vein grafts.
Among the findings:
One of the 11 deaths was caused by stent thrombosis 13 months after stent placement.
Seven of the 11 deaths were considered cardiac deaths, including three sudden cardiac deaths.
One patient in the Cypher arm had an angiographically documented, non-fatal myocardial infarction caused by stent thrombosis.
The angiographically documented late-stent-thrombosis rate was 5% in the Cypher arm versus zero in the bare metal arm (NS).
The rate of confirmed plus possible stent thrombosis was 13% in the Cypher arm versus zero in the bare-metal arm (P=0.022) but again the numbers were small-two confirmed, three suspected.
Although this finding is only the latest report linking drug-eluting stents to increased late mortality, Steven G. Ellis, M.D., of the Cleveland Clinic, in a JACC editorial, pointed out that the finding comes from a very small study of patients that represent a small subset of drug-eluting stent patients -- no more than 8%.
Dr. Ellis said there were, however, a number of lessons to be learned from Dr. Vermeersch and colleagues, including the now familiar refrain that the FDA should "require larger trials, with broader entry criteria, better reflecting the type of patients who might be treated once devices are approved, for trials intended for device approval recommendation."
Likewise important is the acknowledgement that studies such as this, i.e. post hoc analyses that answer questions not posed by the original study design, "should be considered hypothesis generating."
He also pointed out that "it is quite possible, if not likely, that there is no excess risk. In the meantime, however, the cautious physician might well wish to refrain from using sirolimus-eluting stents in saphenous-vein grafts whose closure might be expected to lead to a large infarction."
Finally, Dr. Ellis had a stern admonition for all investigators to remember that it was their responsibility to "education the media in a balanced fashion about their results so that patients attempting to inform themselves and become involved in their own medical decisions are not misled. This, unfortunately, has not always been the case recently."
Neither Dr. Vermeersch nor Dr. Ellis disclosed any financial conflicts.Primary source: Journal of the American College of CardiologySource reference: Vermeersch P et al "Increased Late Mortality After Sirolimus-Eluting Stents Versus Bare-Metal Stents in Diseased Saphenous Vein Grafts Results from Randomized DELAYED RRISC Trial" J Am Coll Cardiol 2007; 50:261-267. Additional source: Journal of the American College of CardiologySource reference: Ellis SG "'Crying Fire in a Theater' or a 'Confirmatory Sighting?'" J Am Coll Cardiol 2007: 50: 268-269.