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Neth Heart J. 2010 September; 18(9): 451–453.
PMCID: PMC2941132

Would SYNTAX have been a positive trial if XIENCE V had been used instead of TAXUS?

A meta-analysis of a first-generation vs. a second-generation drug-eluting stent system

Abstract

Treatment options for coronary revascularisation include percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). In the ‘synergy between PCI with TAXUS and cardiac surgery (SYNTAX)’ trial, PCI and CABG using state-of-the-art techniques (using paclitaxel-eluting stents and arterial grafts, respectively) were compared in the treatment of complex coronary artery disease. In Syntax, PCI was inferior to CABG at one year, entirely due to an increased repeat intervention rate. We hypothesised that the use of a superior drug-eluting stent system could reduce the need for repeat intervention. (Neth Heart J 2010;18:451–3.)

Keywords: Percutaneous Coronary Intervention, Coronary Artery Bypass Surgery, Drug Eluting Stents, Coronary Artery Disease, Meta-analysis

Contemporary treatment options for coronary revascularisation include percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Over the past decades, PCI has evolved from a treatment for single-vessel coronary artery disease into a real alternative to CABG for treatment of complex multivessel coronary artery disease. The design of coronary stent systems has improved continuously since the introduction of the first commercially available coronary stent, the Palmaz-Schatz stent.1 From the bare metal stent period we have moved into the present era of drug-eluting stents (DES). Many DES are currently available, all composed of similar components (a stent platform, a polymer carrying the drug and a drug). However, their clinical effectiveness differs widely. The Synergy between PCI with TAXUS and cardiac surgery (SYNTAX) trial investigated whether PCI with DES (paclitaxel-eluting stents [PES], TAXUS, Boston Scientific, Natick, MA) was non-inferior to CABG in the treatment of complex coronary artery disease.2 The primary clinical endpoint was a composite of major adverse cardiac and cerebrovascular events (MACCE) consisting of death from any cause, stroke, myocardial infarction, or repeat revascularisation. In SYNTAX, PCI was inferior to CABG at one year, entirely due to an increased repeat intervention rate. We hypothesised that the use of a superior next-generation DES could reduce the need for repeat intervention after PCI. To investigate whether the everolimus-eluting stent (EES) (XIENCE V, Abbott Vascular, Santa Clara, CA, also distributed as PROMUS, Boston Scientific, Natick, MA) is superior to the PES we performed a random-effects meta-analysis of the four randomised clinical trials comparing EES with PES for which one-year results have been published.3-6 We studied the following safety and efficacy endpoints: death from any cause, myocardial infarction, target lesion revascularisation, and definite or probable stent thrombosis by Academic Research Consortium (ARC)7 definitions. In the four trials, a total of 4194 patients were randomised to EES and 2489 patients to PES. Results of the meta-analysis are shown in figure 1. At one year, patients treated with the EES had significantly lower rates of myocardial infarction (risk ratio [RR] 0.57), target lesion revascularisation (RR 0.49), and ARC definite or probable stent thrombosis (RR 0.36). These results could be explained by differences between both DES in the underlying stent platforms, differences in the drug and differences in the polymer eluting the drug (table 1).

Figure 1
Outcomes from randomised trials comparing the everolimus-eluting stent (EES) with the paclitaxel-eluting stent (PES). Size of data markers indicates the weight of the study.
Table 1
Differences in stent design between the everolimus-eluting stent (EES) and the paclitaxel-eluting stent (PES).

In SYNTAX, PCI would have been non-inferior to CABG if the 95% upper limit of the confidence interval (CI) for the difference in MACCE was below the prespecified delta of 6.6%. We calculated the minimal reduction in MACCE needed in the PCI group to meet the non-inferiority criterion. A hypothetical reduction of 2.2% in one-year MACCE (20 events/891 patients) would reduce the MACCE rate for PCI to 15.6% (139 events/891 patients). Assuming an unchanged MACCE rate for CABG (105 events/849 patients, 12.4%), this would have resulted in non-inferiority (absolute difference in MACCE 3.2%, 95% CI 0.0 to 6.5%).2

Based on the meta-analysis, the use of EES instead of PES in SYNTAX might have led to a total reduction of approximately 81 events in the PCI group (hypothetical relative reductions of 51% in repeat intervention and 43% in myocardial infarction).2 This is clearly more than the needed reduction of 20 events to achieve non-inferiority between CABG and PCI in SYNTAX. However, since patients in SYNTAX had relatively complex lesions compared with patients in the randomised trials included in our meta-analysis, these results cannot be directly extrapolated to SYNTAX. Moreover, the observed reduction in target lesion revascularisation might not directly reflect a reduction in overall repeat intervention. Finally, patients with diabetes mellitus may not benefit from EES use as a subgroup analysis from the SPIRIT IV trial showed comparable one-year results for EES and PES in diabetic patients.6

Ultimately, whether PCI with EES is non-inferior to CABG can only be determined by another large randomised controlled trial such as the recently announced Evaluation of XIENCE Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial which will randomise 2500 patients with unprotected left main disease to CABG or PCI with EES.

PCI versus CABG: It isn’t over yet!

Disclosures

Dr. Henriques received a research grant from Abbott Vascular, Professor Piek is a member of the Medical Advisory Board of Abbott Vascular, Professor Stone is a member of the Advisory Board for Boston Scientific and Abbott Vascular.

References

1. Schatz RA, Palmaz JC, Tio FO, Garcia F, Garcia O, Reuter SR. Balloon-expandable intracoronary stents in the adult dog. Circulation. 1987;76:450-7. [PubMed]
2. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961-72. [PubMed]
3. Ruygrok PN, Desaga M, Van Den Branden F, Rasmussen K, Suryapranata H, Dorange C, et al. One year clinical follow-up of the XIENCE V Everolimus-eluting stent system in the treatment of patients with de novo native coronary artery lesions: the SPIRIT II study. EuroIntervention. 2007;3:315-20. [PubMed]
4. Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. JAMA. 2008;299:1903-13. [PubMed]
5. Kedhi E, Joesoef KS, McFadden E, Wassing J, van Mieghem C, Goedhart D, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet. 2010;375:201-9. [PubMed]
6. Stone GW, Rizvi A, Newman W, Mastali K, Wang JC, Caputo R, et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med. 2010;362:1663-74. [PubMed]
7. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115:2344-51. [PubMed]

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