EDITORIAL COMMENT
Paclitaxel Versus SirolimusThe Battle Is Still Ongoing*
Christodoulos Stefanadis, MD, FACC* and
Konstantinos Toutouzas, MD
Department of Cardiology, Athens Medical School, Athens, Greece
* Reprint requests and correspondence: Dr. Christodoulos Stefanadis, Department of Cardiology, Athens Medical School, 9 Tepeleniou str., 15454 Paleo Psychico, Athens, Greece (Email: chstefan{at}med.uoa.gr).
Key Words: stent thrombosis • drug-eluting stents • Cypher • Taxus
Drug-eluting stents (DES) have proven to be superior to bare-metal stents in several randomized trials in terms of angiographic restenosis rate and the incidence of major adverse cardiac events, although they are associated with an increased late thrombosis rate. These important findings changed interventional cardiology, as more complex procedures are being performed. We have to keep in mind that these essential data have arisen from large randomized trials, in which the safety and efficacy of the first-generation DES was investigated. The primary efficacy end point was the angiographic restenosis rate, and indeed both the sirolimus-eluting stent (SES) and the paclitaxel-eluting stent (PES) proved to be effective (1–4). These randomized trials really changed the field of interventional cardiology, and thus SES and PES are the most widely used DES to date.
Thereafter the question emerged: Which stent is associated with better safety and efficacy? Randomized trials for head-to-head comparison of SES and PES were performed and have shown clearly that: 1) there is no difference in the incidence of death and cardiac death; and 2) PES are associated with more late loss compared with SES (5,6); furthermore, in one study the angiographic restenosis rate was greater in the PES group (6.6% vs. 11.7%, p = 0.02) (6).
Registries have definite advantages and disadvantages. They can provide significant information regarding the real-life clinical practice, and thus evaluate the clinical application of several therapeutic strategies. The evaluation however of the safety and the efficacy of 2 or 3 different approaches is extrapolated, because the interference of the heterogeneity of protocols, subjects, and entry criteria in the final results cannot be completely abolished. These are important reasons for the usual failure of registries and meta-analyses to predict the outcomes of large randomized clinical trials. Thus, the conclusions of the mentioned large registry contribute significantly to our knowledge, but these results need to be considered under the prism of the mentioned methodological limitations (7).
Post-hoc meta-analyses and registries have been used to compare the safety and efficacy of these 2 most widely used DES. In this issue of the Journal, Kaltolft et al. (7) report the results of the Western Denmark Heart Registry, and conclude that during a 2-year follow-up period, PES are associated with increased mortality because of an increased rate of myocardial infarction after 12 months of follow-up. Moreover, they mention that the clinically driven target lesion revascularization rates were similar between SES and PES.
The excess of mortality rate in the PES group has not been confirmed by previous randomized trials. The recent analysis of the pivotal blinded, randomized, controlled trials of both PES and SES did not show any difference in the incidence of definite or probable stent thrombosis occurring 1 to 4 years after the procedure using the Academic Research Consortium (8). These results are in accordance with the recently reported rate of stent thrombosis of the SORT OUT II (Danish Organization on Randomized Trials With Clinical Outcome) randomized trial performed in Denmark (9). Thus, the lower incidence of stent thrombosis in the SES group can be attributed to differences in the baseline demographic characteristics. Indeed, more patients with acute coronary syndromes were treated with PES. In addition, the baseline comorbidity index score was higher in the PES group (Table 1) (7). Another shortcoming is the retrospective application of the new definitions of stent thrombosis. The increased rate of myocardial infarction cannot be exclusively attributed to stent thrombosis, as the authors also mention in the Discussion. Finally, the designed length of double antiplatelet therapy and related compliance for individual patients were not strictly followed.
Similar limitations possibly led to the controversial results of another larger registry. In the first report of the SCAAR (Swedish Coronary Angiography and Angioplasty Registry), DES were associated with an increased rate of death and myocardial infarction compared with bare-metal stents (10). The inclusion of more patients with a longer follow-up period showed no difference in mortality or myocardial infarction (11).
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Are All DES Equal?
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There are several differences in the stent design, the polymer, and the drug eluted in the DES. Whether these differences have an impact in the clinical outcome of the treated patients has not been confirmed in large prospective clinical trials with the statistical power to identify differences in the rate of stent thrombosis and myocardial infarction. The most important contribution of large registries is to confirm that the current practice, as established by the randomized trials, is indeed in the right direction. The results of the Western Denmark Heart Registry confirmed that DES are associated with a lower need for target lesion revascularization compared with bare-metal stents, without an accompanied increase in mortality (7).
The progress of DES is substantial, and several new platforms with new drugs are being tested. The new PES (Liberte vs. Express, Boston Scientific Corp., Natick, Massachusetts) in more complex lesions (Taxus Atlas Small Vessel and Long Lesion) was associated with a noninferior safety profile and a reduced rate of myocardial infarction (12). These results were also confirmed by the subgroup analysis of the SCAAR study (11).
Despite the differences in the technical characteristics between the currently available stents, we need large randomized trials adequately powered to reveal differences in the clinical end points. The DES are still the primary tool for preventing restenosis, and we expect that the advancement of technology will soon resolve the drawbacks of currently available stents.
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Footnotes
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* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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References
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1. Ellis SG, Colombo A, Grube E, et al. Incidence, timing, and correlates of stent thrombosis with the polymeric paclitaxel drug-eluting stent: a TAXUS II, IV, V, and VI meta-analysis of 3,445 patients followed for up to 3 years J Am Coll Cardiol 2007;49:1043-1051.[Abstract/Free Full Text]2. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery N Engl J Med 2003;349:1315-1323.[CrossRef][Web of Science][Medline] 3. Schampaert E, Moses JW, Schofer J, et al. Sirolimus-eluting stents at two years: a pooled analysis of SIRIUS, E-SIRIUS, and C-SIRIUS with emphasis on late revascularizations and stent thromboses Am J Cardiol 2006;98:36-41.[CrossRef][Medline] 4. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents N Engl J Med 2007;356:998-1008.[CrossRef][Medline] 5. Morice MC, Colombo A, Meier B, et al. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial JAMA 2006;295:895-904.[Abstract/Free Full Text] 6. Windecker S, Remondino A, Eberli FR, et al. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization N Engl J Med 2005;353:653-662.[CrossRef][Web of Science][Medline] 7. Kaltolft A, Jensen LO, Maeng M, et al. 2-year clinical outcomes after implantation of sirolimus-eluting, paclitaxel-eluting, and bare-metal coronary stents: results from the WDHR (Western Denmark Heart Registry) J Am Coll Cardiol 2009;53:658-664.[Abstract/Free Full Text] 8. Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents N Engl J Med 2007;356:1020-1029.[CrossRef][Medline] 9. Galloe AM, Thuesen L, Kelbaek H, et al. Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial JAMA 2008;299:409-416.[Abstract/Free Full Text] 10. Lagerqvist B, James SK, Stenestrand U, Lindback J, Nilsson T, Wallentin L. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden N Engl J Med 2007;356:1009-1019.[CrossRef][Medline] 11. Stefan J. SCAAR—Long-term mortality after drug-eluting stents in Sweden, an additional year of follow-up Presented at: Congress of European Society of Cardiology 2007; Vienna 2007September 2. 12. Turco MA, Ormiston JA, Popma JJ, et al. Polymer-based, paclitaxel-eluting TAXUS Liberte stent in de novo lesions: the pivotal TAXUS ATLAS trial J Am Coll Cardiol 2007;49:1676-1683.[Abstract/Free Full Text]
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Are All DES Equal?
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