A Meta-Analysis of 16 Randomized Trials of Sirolimus-Eluting Stents Versus Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease

A Meta-Analysis of 16 Randomized Trials of Sirolimus-Eluting Stents Versus Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease

Kastrati Adnan , Schömig Albert
Interventional Cardiology 2007
Published: October 2007
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Drug-eluting stents (DES) have largely resolved the problem of restenosis, which is the major limitation of plain balloon angioplasty and bare-metal stenting.1 While several DES platforms have been evaluated in the setting of randomised studies and used in clinical practice, most of the accumulated evidence is related to sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES).2 These devices are the only DES approved by the US Food and Drug Administration (FDA).3

DES have been linked to a higher risk of late stent thrombosis compared with bare-metal stents (BMS),4,5 a phenomenon that was not identified in the initial trials with short- to mid-term follow-up.6 Furthermore, several studies have suggested that SES and PES may be associated with increased mortality and higher rates of myocardial infarction (MI).4,7–9 Serious concerns have been raised regarding the long-term safety of these DES,10–12 although more comprehensive, patient-based metaanalyses do not justify these concerns.13,14

SES and PES differ importantly with respect to polymer coating and antiproliferative drugs, which may have an impact on the risk of late adverse events associated with these devices. Recently, the results of two meta-analyses suggested that the risk of late thrombosis or death might be different between SES and PES;4,9 however, this difference was inferred from indirect comparisons from trials comparing SES and PES with BMS separately.4,9 Therefore, it remains uncertain whether there are any differences between SES and PES with regard to their long-term safety profile. This uncertainty notwithstanding, a prior meta-analysis including six trials on 3,669 patients followed up for up to one year showed that SES are superior to PES in reducing the risk of restenosis.15 Whether the benefit of SES is maintained beyond this period also remains unknown.

Direct-comparison meta-analysis of randomised trials has the potential to increase the power and improve the precision of treatment effects.16 The availability of individual patient data is the ‘gold standard’ for the analysis of time-to-event or survival data.17 Therefore, we performed a comprehensive meta-analysis with a large emphasis on individual patient data from all clinical trials that have evaluated the long-term outcomes of SES and PES after coronary implantation.

Results
Sixteen randomised trials on a total of 8,695 patients were analysed. The patients were representative of the whole clinical spectrum of coronary artery disease. Individual patient data were available from 11 trials, including 5,562 patients who were followed up for a median of 24.3 months (25th and 75th percentiles: 18.4 and 28.7 months, respectively) in the SES group and 24.3 months (25th and 75th percentiles: 18.3 and 28.5 months, respectively) in the PES group (p=0.51).18–28

Re-intervention, the primary efficacy end-point, was needed in 295 patients in the SES group versus 380 patients in the PES group. Allocation to the SES group was associated with a hazard ratio (HR) for re-intervention of 0.74 (95% confidence interval (CI) 0.63–0.87; p<0.001). There was no significant heterogeneity across trials (p=0.39). The sensitivity analysis yielded HRs that ranged from 0.69 (95% CI 0.59–0.82) to 0.78 (95% CI 0.66–0.92) and were not significantly different from the overall HR (p≥0.58). There was no significant interaction between the treatment effect and inclusion of follow-up angiography in the study protocol (p=0.10). When the analysis was confined to the trials for which individual patient data were available, SES were associated with an HR for re-intervention of 0.72 (95% CI 0.61–0.86; p<0.001). Within the first year, the HR was 0.70 (95% CI 0.57–0.85; p<0.001); after the first year, the HR was 0.79 (95% CI 0.58–1.09; p=0.15). The 30-month probability of re-intervention was 9.5% in the SES group and 12.7% in the PES group.

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References:
  1. Babapulle MN, Joseph L, Belisle P, et al., A hierarchical Bayesian meta-analysis of randomised clinical trials of drugeluting stents, Lancet, 2004;364:583–91.
  2. Eisenberg MJ, Konnyu KJ, Review of randomized clinical trials of drug-eluting stents for the prevention of in-stent restenosis, Am J Cardiol, 2006;98:375–82.
  3. Ray GM, Nawarskas JJ, Frishman WH, The paclitaxel-eluting stent in percutaneous coronary intervention: part II. Comparison with the sirolimus-eluting stent, economics, and unanswered questions, Cardiol Rev, 2006;14:143–50.
  4. Bavry AA, Kumbhani DJ, Helton TJ, et al., Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials, Am J Med, 2006;119:1056–61.
  5. McFadden EP, Stabile E, Regar E, et al., Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy, Lancet, 2004;364:1519–21.
  6. Moreno R, Fernandez C, Hernandez R, et al., Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies, J Am Coll Cardiol, 2005;45:954–9.
  7. Pfisterer M, Brunner-La Rocca HP, Buser PT, et al., Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents, J Am Coll Cardiol, 2006;48:2584–91.
  8. Camenzind E, Safety of Drug-Eluting Stents: Insights From Meta Analysis. Available at: http://www.escardio.org/knowledge/congresses/Congress Reports/hotlinesandctus/707009_Camenzind.htm. Accessed 16 February 2007.
  9. Nordmann AJ, Briel M, Bucher HC, Mortality in randomized controlled trials comparing drug-eluting vs. bare metal stents in coronary artery disease: a meta-analysis, Eur Heart J, 2006;27: 2784–2814.
  10. Shuchman M, Trading restenosis for thrombosis? New questions about drug-eluting stents, N Engl J Med, 2006;355: 1949–52.
  11. Wijns WC, Krucoff MW, Increased mortality after implantation of first generation drug-eluting stents: seeing the smoke, where is the fire?, Eur Heart J, 2006;27:2737–9.
  12. Camenzind E, Treatment of in-stent restenosis – back to the future?, N Engl J Med, 2006;355:2149–51.
  13. Kastrati A, Mehilli J, Pache J, et al., Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents, N Engl J Med, 2007;356:1030–39.
  14. Stone GW, Perspectives on drug-eluting stent safety and efficacy with regulatory recommendations. Paper presented at: FDA Circulatory System Devices Panel of the Medical Devices Advisory Committee, 7–8 December 2006, Washington, DC.
  15. Kastrati A, Dibra A, Eberle S, et al., Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials, JAMA, 2005;294: 819–25.
  16. Egger M, Ebrahim S, Smith GD, Where now for meta-analysis?, Int J Epidemiol, 2002;31:1–5.
  17. Simmonds MC, Higgins JP, Stewart LA, et al., Meta-analysis of individual patient data from randomized trials: a review of methods used in practice, Clin Trials, 2005;2:209–17.
  18. Kaiser C, Brunner-La Rocca HP, Buser PT, et al., Incremental cost-effectiveness of drug-eluting stents compared with a thirdgeneration bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitats Trial (BASKET), Lancet, 2005;366:921–9.
  19. de Lezo J, Medina A, Pan M, et al., Drug-eluting stents for complex lesions: randomized rapamycin versus paclitaxel CORPAL study (abstr), J Am Coll Cardiol, 2005;45:75A.
  20. Di Lorenzo E, Varricchio A, Lanzillo T, et al., Paclitaxel and sirolimus stent implantation in patients with acute myocardial infarction (abstr), Circulation, 2005;112:U538.
  21. Kastrati A, Mehilli J, von Beckerath N, et al., Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial, JAMA, 2005;293: 165–71.
  22. Dibra A, Kastrati A, Mehilli J, et al., Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients, N Engl J Med, 2005;353:663–70.
  23. Mehilli J, Dibra A, Kastrati A, et al., Randomized trial of paclitaxel- and sirolimus-eluting stents in small coronary vessels, Eur Heart J, 2006;27:260–66.
  24. Kim YH, Park SW, Lee SW, et al., Sirolimus-eluting stent versus paclitaxel-eluting stent for patients with long coronary artery disease, Circulation, 2006;114:2148–53.
  25. Lee JH, Kim HS, Lee SW, et al., Prospective randomized trial of sirolimus- versus paclitaxel-eluting stents for the treatment of acute ST-elevation myocardial infarction. Paper presented at: American College of Cardiology 55th Annual Scientific Session, 11–14 March 2006, Atlanta, GA.
  26. Morice MC, Colombo A, Meier B, et al., Sirolimus- vs paclitaxeleluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial, JAMA, 2006;295:895–904.
  27. Windecker S, Remondino A, Eberli FR, et al., Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization, N Engl J Med, 2005;353:653–62.
  28. Goy JJ, Stauffer JC, Siegenthaler M, et al., A prospective randomized comparison between paclitaxel and sirolimus stents in the real world of interventional cardiology: the TAXI trial, J Am Coll Cardiol, 2005;45:308–11.
  29. Joner M, Finn AV, Farb A, et al., Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk, J Am Coll Cardiol, 2006;48:193–202.
  30. Finn AV, Kolodgie FD, Harnek J, et al., Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents, Circulation, 2005;112:270–78.
  31. Daemen J, Wenaweser P, Tsuchida K, et al., Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxeleluting stents in routine clinical practice. Data from a large twoinstitutional cohort study, Lancet, 2007;369:667–78.
  32. Grines CL, Bonow RO, Casey DE Jr., et al., Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians, J Am Coll Cardiol, 2007;49:734–9.

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