News:Drug-Eluting Stents: Meta-analysis Demonstrates Superior Clinical Performance of Sirolimus-eluting Stents (SES) Over Bare-metal Stents (BMS) and Paclitaxel-eluting Stents (PES)

September 17, 2007 By Scott P. Williams [mailto:swilliams@perfuse.org] and Alexandra M. Palmer [mailto:apalmer@perfuse.org]

The analysis included patients with coronary artery disease and evaluated the safety and efficacy of the stents. Safety endpoints included mortality, myocardial infarction and definite stent thrombosis, while efficacy was assessed is based upon target lesion revascularization.

Stettler and Wandel et al. conducted a metanalysis of thirty-eight randomized controlled trials which encompassed 18,023 patients, with a follow-up of up to four years. Additional data for twenty-nine of the thirty-eight trials were supplied by trialists and manufacturers.

The mortality was similar among the three stent groups. Specifically, the hazard ratios were 1.00 (95% credibility interval (CI): 0.81-1.25), 1.03 (95% CI: 0.84-1.22), and 0.96 (95% CI: 0.83-1.24) for SES versus BMS, PES versus BMS and SES versus PES, respectively. Likewise, there was no significant difference in the risk of definite stent thrombosis among the three stent types (over the entire course from 0 days to 4 years).

However, there were differences in other results. In comparison to BMS and PES, SES was associated with a lower risk of myocardial infarction (SES versus BMS: hazard ratio = 0.83, 95% CI = 0.71-1.00, p = 0.045; SES versus PES: hazard ratio = 0.81, 95% CI = 0.66-0.97, p = 0.030). Furthermore, there was an increase in the risk of late definite stent thrombosis with the use of PES (PES versus BMS: hazard ratio = 2.11, 95% CI = 1.19-4.23, p = 0.017; PES versus SES: hazard ratio = 1.85, 95% CI = 1.02-3.85, p = 0.041).

This study comes on the heals of prior reports of late stent thrombosis associated with the use of drug-eluting stents. Stettler and Wandel et al. build upon previous studies by comparing both DES with BMS and the two DES to each other. In doing so, they conclude that there is no significant difference in the risk of mortality associated with either DES and that associated with BMS. Finally, and perhaps most importantly, the study suggests in a non-randomized fashion that SES may be associated with a lower risk of MI compared to BMS and DES.

Commenting on the results of the study for heartwire, Dr Sanjay Kaul (Cedars-Sinai Medical Center, Los Angeles, CA) said this meta-analysis, one of the largest and most robust meta-analyses of drug-eluting stents to date, is "methodologically rigorous and comprehensive in its assessment of the evidence." He disputes, however, the conclusions reached by the authors, that the sirolimus-eluting stent is clinically superior to the paclitaxel-eluting stent or bare-metal stents.

"The authors should know best that meta-analyses are useful for generating but not for concluding hypotheses," said Kaul. "Only adequately powered larger and longer randomized controlled trials that are designed to evaluate safety and efficacy in populations that reflect 'real-world' clinical practice will reliably adjudicate the question."

Until then, said Kaul, the use of drug-eluting stents should be based on a benefit/risk assessment on an individual basis. "In my opinion, a prudent, cost-effective and evidence-based approach would be to limit their use in about one-third of patients undergoing PCI," he added. "I am reassured to note that the current DES utilization has undergone a 'correction factor' and is now trending in the right direction."

The study is limited by wide confidence intervals that prevent any definite conclusions. In addition, the researchers note that complex patients (i.e. those with diabetes, renal failure etc.) may have been underrepresented in this study, as is a common problem among most clinical trials and their resulting meta-analyses. Most importantly, there may have been differences in the patients in whom a PES vs an SES were placed, and the results should be interpreted with extreme caution given the non-randomized comparison of the results.

While these results are provocative, meta analytic data are no substitute for large randomized head to head comparisons of SES vs PES.

This analysis was funded by: Swiss National Science Foundation, Johnson & Johnson, Boston Scientific, Medtronic and Abbott Vascular.

References

1. Christoph Stettler MD, Simon Wandel MSc, Sabin Allemann PhD, Prof Adnan Kastrati MD, Prof Marie Claude Morice MD, Prof Albert Schömig MD, Prof Matthias E Pfisterer MD, Prof Gregg W Stone MD, Prof Martin B Leon MD, José Suarez de Lezo MD, Prof Jean-Jacques Goy MD, Prof Seung-Jung Park MD, Manel Sabaté PhD, Maarten J Suttorp PhD, Henning Kelbaek MD, Prof Christian Spaulding MD, Maurizio Menichelli MD, Paul Vermeersch MD, Maurits T Dirksen MD, Pavel Cervinka PhD, Prof Anna Sonia Petronio MD, Alain J Nordmann MD, Prof Peter Diem MD, Prof Bernhard Meier MD, Marcel Zwahlen PhD, Stephan Reichenbach MD, Sven Trelle MD, Prof Stephan Windecker MD and Dr Peter Jüni MD. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. The Lancet 2007 Sep; 370 (9591) 937-948.