Fewer Heart Attacks Reported with Cypher (Sirolimus-Eluting) Stent

BERN, Switzerland, Sept. 14 -- The two major drug-eluting stents and bare-metal devices emerged in a three-way mortality dead heat, according to a meta-analysis of 38 randomized trials conducted by an international team.

There were fewer myocardial infarctions among patients treated with sirolimus-eluting (Cypher) stents compared with patients who received paclitaxel-eluting (Taxus) stents or bare-metal devices, the researchers wrote in the Sept. 15 issue of The Lancet.

But overall results from the meta-analysis found no significant difference in mortality regardless of stent type, concluded Christoph Stettler, M.D., of University of Bern, and colleagues.

There were also no significant differences in the risk of definite stent thrombosis, meaning stent thrombosis confirmed by angiography or autopsy, among the stents but there was an increased risk of late stent thrombosis with the paclitaxel-eluting stent, they wrote.

The 38 trials in the analysis included data from 18,023 patients with a follow-up of up four years.

Dr. Stettler and colleagues used data from all 38 trials to analyze overall mortality, and the combined endpoint of death or MI, but used data from only 37 trials in the analysis of cardiac mortality, 37 trials for the MI analysis, 24 trials for stent thrombosis by Academic Research Consortium (ARC) criteria, 37 trials for per protocol defined stent thrombosis, and 37 trials to in their analysis of target lesion revascularization.

Data from 17 trials contributed to the analysis of sirolimus-eluting stents with bare metal stents, eight trials to the paclitaxel-eluting stent versus bare metal stent analysis, and 15 trials contributed to the analysis of sirolimus-eluting stents with paclitaxel-eluting stents.

This network meta-analysis design "integrated evidence from direct and indirect comparisons while fully preserving randomization," they wrote.

Among the findings:

• The HR for MI with sirolimus-eluting stents was 0.81, 95% credibility interval 0.66-0.97 P=0.030 versus bare-metal stents and 0.83 (95% CI 0.71-1.00 P=0.045) versus the paclitaxel-eluting stent.
• The risk of stent thrombosis after 30 days was twice as higher for the paclitaxel eluting stents compared with bare-metal stents (HR 2.11, 95% CI 1.19-4.23 P=0.017) and 85% higher than the rate with the sirolimus-eluting stent (HR 1.85, 95% CI 0.56-0.84, P=0.041).
• The sirolimus-eluting stent reduced target lesion revascularization by 70% compared with bare metal stents, while the paclitaxel-eluting stent reduced target lesion revascularization by 58% compared with bare-metal stents.

The authors cited their use of standardized definition of outcomes, and "most importantly" the use of the Academic Research Consortium's definition of stent thrombosis, was a major strength of the analysis. (See: TCT: New Definition and Data Make Drug-Eluting Coronary Stents Seem Safer)

That definition, for example, "avoids exclusion of secondary stent thrombosis occurring after a patient had undergone a target lesion revascularization," a practice that favors bare-metal stents, which have a high risk of target lesion revascularization.

In a commentary in the same issue of The Lancet, Mark Webster, M.D., and John Ormiston, M.D., of Auckland City Hospital in New Zealand, wrote that the meta-analysis "is the best current comparison of the two drug-eluting stents," but they pointed out that "an emerging issue with the plethora of meta-analyses is the complexity of the statistics."

Few clinicians, they wrote, "understand the differences between the network or mixed-treatment comparison in Stettler's study and other meta-analytical methods."

Moreover, while the Academic Research Consortium's definition of stent thrombosis was "useful for comparing different types of stents," it may also "substantially underestimate the true rate of thrombosis," Drs. Webster and Ormiston wrote.

Finally, Drs. Webster and Ormiston cautioned that the findings of the analysis may not relate to the real-world experience because the patients in the randomized trials were unlikely to be as sick or have lesions as complicated as patients who regularly get drug-eluting stents in every day clinical practice. They conclude, therefore, that there may be a resurgence of interest in bare-metal stents combined with various oral antiproliferative regimens aimed at reducing the risk of restenosis.