Boston, MA - In the midst of all the renewed excitement over drug-eluting-stent (DES) safety in recent weeks, the two, large, randomized controlled trials that first established the safety and efficacy of DES in acute MI have been published in the New England Journal of Medicine [1,2]. As previously reported by heartwire when the trials were first presented at the American College of Cardiology 2006 Scientific Sessions, Paclitaxel-Eluting Stent versus Conventional Stent in Myocardial Infarction with ST-Segment Elevation (PASSION), comparing the Taxus paclitaxel-eluting stent to a bare Express2 or Liberté stent, showed a nonstatistically significant trend toward reduced clinical events, while the Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated with Balloon Angioplasty (TYPHOON), comparing the Cypher sirolimus-eluting stent to any commercially available stent, showed a significantly lower composite rate of clinical events in DES-treated patients.

At the time, both of the presenters as well as outside observers urged people not to use the two trials to directly compare the two stents, particularly since the trial populations had been different, with more complex lesions/patients enrolled in PASSION and an unexpectedly low MACE rate in the bare-metal-stent group in this trial as well. End points used in the trial were different, too, although on balance, one-year revascularization rates in both trials (defined as target vessel revascularization [TVR] in TYPHOON and target lesion revascularization [TLR] in PASSION) were similar, at 5.6% for the Cypher in TYPHOON and 5.3% for the Taxus in PASSION. Of note, rates of stent thrombosis were higher in the Cypher arm in TYPHOON (at 3.4%) than in the Taxus arm in PASSION (1%), but here again, definitions were different, with the TYPHOON study using a broader definition of late thrombosis.

Now, in an editorial accompanying the two studies, Dr Frans Van de Werf (University of Leuven, Belgium) also cautions against comparisons [3].

"In the PASSION trial, nonsignificant trends in favor of the paclitaxel-eluting stent were found for target lesion revascularization, death, and reinfarction, whereas in the TYPHOON trial, the sirolimus-eluting stent was associated with a significant reduction in the rate of target vessel revascularization, with rates of death and reinfarction very similar to those in the uncoated-stent group. It would be dangerous to conclude from these data that one drug-eluting stent is better than the other in primary PCI, since direct comparisons of the two stents for this indication are not available."

Reiterating all of the differences in design, inclusion criteria, and end-point definitions that thwart comparisons of the two studies, Van de Werf nevertheless concedes that suggestions of a differential impact persist. "The results seem to be in line with those of studies that have compared these two types of stents in elective procedures—namely, lower rates of restenosis and repeated intervention with the sirolimus-eluting stent, without significant differences in myocardial infarction or death."

Van de Werf also points out that follow-up angiography among 174 TYPHOON participants may have prompted additional revascularizations in this trial.

"The data from these two trials indicate that drug-eluting stents can be used safely in the setting of primary PCI and are likely to reduce the need for repeated revascularization. However, the results do not demonstrate that criteria for selecting a drug-eluting stent for this indication should differ from those for elective procedures (eg, diabetes, long lesions, and small vessels)."

Echoing comments also repeated time and again at last week's World Congress of Cardiology 2006 meeting, Van de Werf also underscored the unknown risk posed by late stent thrombosis following DES implantation.

"Because of the cost, the need for prolonged treatment with thienopyridine, and the risk of late stent thrombosis (especially after premature discontinuation of thienopyridine therapy), larger trials with hard clinical end points and longer follow-up are needed before routine implantation of drug-eluting stents can be recommended for all patients undergoing primary PCI."