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Three-year efficacy and safety of new- versus early-generation drug-eluting stents for unprotected left main coronary artery disease insights from the ISAR-LEFT MAIN and ISAR-LEFT MAIN 2 trials

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Abstract

Background

In percutaneous coronary intervention (PCI) patients new-generation drug-eluting stent (DES) has reduced adverse events in comparison to early-generation DES. The aim of the current study was to investigate the long-term clinical efficacy and safety of new-generation DES versus early-generation DES for PCI of unprotected left main coronary artery (uLMCA) disease.

Methods

The patient-level data from the ISAR-LEFT MAIN and ISAR-LEFT MAIN 2 randomized trials were pooled. The clinical outcomes of PCI patients assigned to new-generation DES (everolimus- or zotarolimus-eluting stent) versus early-generation DES (paclitaxel- or sirolimus-eluting stent) were studied. The primary endpoint was the composite of death, myocardial infarction (MI), target lesion revascularization and stroke (MACCE, major adverse cardiac and cerebrovascular event).

Results

In total, 1257 patients were available. At 3 years, the risk of MACCE was comparable between patients assigned to new-generation DES or early-generation DES (28.2 versus 27.5 %, hazard ratio—HR 1.03, 95 % confidence intervals—CI 0.83–1.26; P = 0.86). Definite/probable stent thrombosis was low and comparable between new-generation DES and early-generation DES (0.8 versus 1.6 %, HR 0.52, 95 % CI 0.18–1.57; P = 0.25); in patients treated with new-generation DES no cases occurred beyond 30 days. Diabetes increased the risk of MACCE in patients treated with new-generation DES but not with early-generation DES (P interaction = 0.004).

Conclusions

At 3-year follow-up, a PCI with new-generation DES for uLMCA disease shows comparable efficacy to early-generation DES. Rates of stent thrombosis were low in both groups. Diabetes significantly impacts the risk of MACCE at 3 years in patients treated with new-generation DES for uLMCA disease.

ClinicalTrials.gov Identifiers: NCT00133237; NCT00598637.

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References

  1. Stone GW, Moses JW, Leon MB (2007) Left main drug-eluting stents: natural progression or a bridge too far? J Am Coll Cardiol 50(6):498–500. doi:10.1016/j.jacc.2007.04.055

    Article  CAS  PubMed  Google Scholar 

  2. Authors/Task Force m, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A (2014) 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 35(37):2541–2619. doi:10.1093/eurheartj/ehu278

    Article  Google Scholar 

  3. Bittl JA, He Y, Jacobs AK, Yancy CW, Normand SL, American College of Cardiology Foundation/American Heart Association Task Force on Practice G (2013) Bayesian methods affirm the use of percutaneous coronary intervention to improve survival in patients with unprotected left main coronary artery disease. Circulation 127(22):2177–2185. doi:10.1161/CIRCULATIONAHA.112.000646

    Article  PubMed  Google Scholar 

  4. Athappan G, Patvardhan E, Tuzcu ME, Ellis S, Whitlow P, Kapadia SR (2013) Left main coronary artery stenosis: a meta-analysis of drug-eluting stents versus coronary artery bypass grafting. JACC Cardiovasc Interv 6(12):1219–1230. doi:10.1016/j.jcin.2013.07.008

    Article  PubMed  Google Scholar 

  5. Cassese S, Byrne RA, Tada T, Pinieck S, Joner M, Ibrahim T, King LA, Fusaro M, Laugwitz KL, Kastrati A (2014) Incidence and predictors of restenosis after coronary stenting in 10,004 patients with surveillance angiography. Heart 100(2):153–159. doi:10.1136/heartjnl-2013-304933

    Article  PubMed  Google Scholar 

  6. Tada T, Byrne RA, Simunovic I, King LA, Cassese S, Joner M, Fusaro M, Schneider S, Schulz S, Ibrahim T, Ott I, Massberg S, Laugwitz KL, Kastrati A (2013) Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and second-generation drug-eluting stents: results from a registry of 18,334 patients. JACC Cardiovasc Interv 6(12):1267–1274. doi:10.1016/j.jcin.2013.06.015

    Article  PubMed  Google Scholar 

  7. Beohar N, Davidson CJ, Kip KE, Goodreau L, Vlachos HA, Meyers SN, Benzuly KH, Flaherty JD, Ricciardi MJ, Bennett CL, Williams DO (2007) Outcomes and complications associated with off-label and untested use of drug-eluting stents. JAMA 297(18):1992–2000. doi:10.1001/jama.297.18.1992

    Article  CAS  PubMed  Google Scholar 

  8. Joner M, Nakazawa G, Finn AV, Quee SC, Coleman L, Acampado E, Wilson PS, Skorija K, Cheng Q, Xu X, Gold HK, Kolodgie FD, Virmani R (2008) Endothelial cell recovery between comparator polymer-based drug-eluting stents. J Am Coll Cardiol 52(5):333–342. doi:10.1016/j.jacc.2008.04.030

    Article  CAS  PubMed  Google Scholar 

  9. Bangalore S, Toklu B, Amoroso N, Fusaro M, Kumar S, Hannan EL, Faxon DP, Feit F (2013) Bare metal stents, durable polymer drug eluting stents, and biodegradable polymer drug eluting stents for coronary artery disease: mixed treatment comparison meta-analysis. BMJ 347:f6625. doi:10.1136/bmj.f6625

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kang SH, Park KW, Kang DY, Lim WH, Park KT, Han JK, Kang HJ, Koo BK, Oh BH, Park YB, Kandzari DE, Cohen DJ, Hwang SS, Kim HS (2014) Biodegradable-polymer drug-eluting stents vs. bare metal stents vs. durable-polymer drug-eluting stents: a systematic review and Bayesian approach network meta-analysis. Eur Heart J 35(17):1147–1158. doi:10.1093/eurheartj/eht570

    Article  CAS  PubMed  Google Scholar 

  11. Stefanini GG, Byrne RA, Serruys PW, de Waha A, Meier B, Massberg S, Juni P, Schomig A, Windecker S, Kastrati A (2012) Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials. Eur Heart J 33(10):1214–1222. doi:10.1093/eurheartj/ehs086

    Article  CAS  PubMed  Google Scholar 

  12. Mehilli J, Kastrati A, Byrne RA, Bruskina O, Iijima R, Schulz S, Pache J, Seyfarth M, Massberg S, Laugwitz KL, Dirschinger J, Schomig A, Stenting L-MI, Angiographic Results: Drug-Eluting Stents for Unprotected Coronary Left Main Lesions Study I (2009) Paclitaxel- versus sirolimus-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 53(19):1760–1768. doi:10.1016/j.jacc.2009.01.035

    Article  PubMed  Google Scholar 

  13. Mehilli J, Richardt G, Valgimigli M, Schulz S, Singh A, Abdel-Wahab M, Tiroch K, Pache J, Hausleiter J, Byrne RA, Ott I, Ibrahim T, Fusaro M, Seyfarth M, Laugwitz KL, Massberg S, Kastrati A, Investigators I-L-MS (2013) Zotarolimus- versus everolimus-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 62(22):2075–2082. doi:10.1016/j.jacc.2013.07.044

    Article  CAS  PubMed  Google Scholar 

  14. Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, Naidu SS, Ohman EM, Smith PK (2014) 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 64(18):1929–1949. doi:10.1016/j.jacc.2014.07.017

    Article  PubMed  Google Scholar 

  15. Morice MC, Serruys PW, Kappetein AP, Feldman TE, Stahle E, Colombo A, Mack MJ, Holmes DR, Choi JW, Ruzyllo W, Religa G, Huang J, Roy K, Dawkins KD, Mohr F (2014) Five-year outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial. Circulation 129(23):2388–2394. doi:10.1161/CIRCULATIONAHA.113.006689

    Article  PubMed  Google Scholar 

  16. Ahn JM, Roh JH, Kim YH, Park DW, Yun SC, Lee PH, Chang M, Park HW, Lee SW, Lee CW, Park SW, Choo SJ, Chung C, Lee J, Lim DS, Rha SW, Lee SG, Gwon HC, Kim HS, Chae IH, Jang Y, Jeong MH, Tahk SJ, Seung KB, Park SJ (2015) Randomized trial of stents versus bypass surgery for left main coronary artery disease: 5-year outcomes of the PRECOMBAT study. J Am Coll Cardiol 65(20):2198–2206. doi:10.1016/j.jacc.2015.03.033

    Article  PubMed  Google Scholar 

  17. Boudriot E, Thiele H, Walther T, Liebetrau C, Boeckstegers P, Pohl T, Reichart B, Mudra H, Beier F, Gansera B, Neumann FJ, Gick M, Zietak T, Desch S, Schuler G, Mohr FW (2011) Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis. J Am Coll Cardiol 57(5):538–545. doi:10.1016/j.jacc.2010.09.038

    Article  PubMed  Google Scholar 

  18. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R (2006) Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 48(1):193–202. doi:10.1016/j.jacc.2006.03.042

    Article  PubMed  Google Scholar 

  19. Finn AV, Nakazawa G, Joner M, Kolodgie FD, Mont EK, Gold HK, Virmani R (2007) Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler Thromb Vasc Biol 27(7):1500–1510. doi:10.1161/ATVBAHA.107.144220

    Article  CAS  PubMed  Google Scholar 

  20. Bangalore S, Kumar S, Fusaro M, Amoroso N, Attubato MJ, Feit F, Bhatt DL, Slater J (2012) Short- and long-term outcomes with drug-eluting and bare-metal coronary stents: a mixed-treatment comparison analysis of 117,762 patient–years of follow-up from randomized trials. Circulation 125(23):2873–2891. doi:10.1161/CIRCULATIONAHA.112.097014

    Article  CAS  PubMed  Google Scholar 

  21. Palmerini T, Biondi-Zoccai G, Della Riva D, Mariani A, Sabate M, Smits PC, Kaiser C, D’Ascenzo F, Frati G, Mancone M, Genereux P, Stone GW (2014) Clinical outcomes with bioabsorbable polymer- versus durable polymer-based drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol 63(4):299–307. doi:10.1016/j.jacc.2013.09.061

    Article  CAS  PubMed  Google Scholar 

  22. Akin I, Hochadel M, Abdel-Wahab M, Senges J, Richardt G, Schneider S, Tebbe U, Kuck KH, Nienaber CA (2013) Clinical outcomes of different first- and second-generation drug-eluting stents in routine clinical practice: results from the prospective multicenter German DES.DE registry. Clin Res Cardiol 102(5):371–381. doi:10.1007/s00392-013-0546-5

    Article  CAS  PubMed  Google Scholar 

  23. Akin I, Naber C, Sabin G, Hochadel M, Senges J, Kuck KH, Nienaber C, Richardt G, Tolg R (2013) Outcome of percutaneous coronary intervention with drug-eluting stents in unprotected left main versus non-left main native coronary artery disease: results from the prospective multicenter German DES.DE registry. Clin Res Cardiol 102(9):679–686. doi:10.1007/s00392-013-0582-1

    Article  CAS  PubMed  Google Scholar 

  24. Campos CM, Christiansen EH, Stone GW, Serruys PW (2015) The EXCEL and NOBLE trials: similarities, contrasts and future perspectives for left main revascularisation. EuroIntervention 11(Suppl V):V115–V119. doi:10.4244/EIJV11SVA26

    Article  PubMed  Google Scholar 

  25. De la Torre Hernandez JM, Alfonso F, Sanchez Recalde A, Jimenez Navarro MF, Perez de Prado A, Hernandez F, Abdul-Jawad Altisent O, Roura G, Garcia Camarero T, Elizaga J, Rivero F, Gimeno F, Calvino R, Moreu J, Bosa F, Rumoroso JR, Bullones JA, Gallardo A, Fernandez Diaz JA, Ruiz Arroyo JR, Aragon V, Masotti M, Group E-LS (2013) Comparison of paclitaxel-eluting stents (Taxus) and everolimus-eluting stents (Xience) in left main coronary artery disease with 3 years follow-up (from the ESTROFA-LM registry). Am J Cardiol 111(5):676–683. doi:10.1016/j.amjcard.2012.11.019

    Article  PubMed  Google Scholar 

  26. Kappetein AP, Feldman TE, Mack MJ, Morice MC, Holmes DR, Stahle E, Dawkins KD, Mohr FW, Serruys PW, Colombo A (2011) Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial. Eur Heart J 32(17):2125–2134. doi:10.1093/eurheartj/ehr213

    Article  PubMed  Google Scholar 

  27. Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Yoon SH, Park HW, Chang M, Lee JY, Kang SJ, Lee SW, Lee CW, Park SW (2015) Temporal trends in revascularization strategy and outcomes in left main coronary artery stenosis: data from the ASAN Medical Center-Left MAIN Revascularization registry. Circ Cardiovasc Interv 8(3):e001846. doi:10.1161/CIRCINTERVENTIONS.114.001846

    Article  PubMed  Google Scholar 

  28. Hildick-Smith D, de Belder AJ, Cooter N, Curzen NP, Clayton TC, Oldroyd KG, Bennett L, Holmberg S, Cotton JM, Glennon PE, Thomas MR, Maccarthy PA, Baumbach A, Mulvihill NT, Henderson RA, Redwood SR, Starkey IR, Stables RH (2010) Randomized trial of simple versus complex drug-eluting stenting for bifurcation lesions: the British Bifurcation Coronary Study: old, new, and evolving strategies. Circulation 121(10):1235–1243. doi:10.1161/CIRCULATIONAHA.109.888297

    Article  CAS  PubMed  Google Scholar 

  29. Farooq V, Serruys PW, Zhang Y, Mack M, Stahle E, Holmes DR, Feldman T, Morice MC, Colombo A, Bourantas CV, de Vries T, Morel MA, Dawkins KD, Kappetein AP, Mohr FW (2013) Short-term and long-term clinical impact of stent thrombosis and graft occlusion in the SYNTAX trial at 5 years: synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery trial. J Am Coll Cardiol 62(25):2360–2369. doi:10.1016/j.jacc.2013.07.106

    Article  PubMed  Google Scholar 

  30. Bangalore S, Toklu B, Feit F (2014) Outcomes with coronary artery bypass graft surgery versus percutaneous coronary intervention for patients with diabetes mellitus: can newer generation drug-eluting stents bridge the gap? Circ Cardiovasc Interv 7(4):518–525. doi:10.1161/CIRCINTERVENTIONS.114.001346

    Article  PubMed  Google Scholar 

  31. Verma S, Farkouh ME, Yanagawa B, Fitchett DH, Ahsan MR, Ruel M, Sud S, Gupta M, Singh S, Gupta N, Cheema AN, Leiter LA, Fedak PW, Teoh H, Latter DA, Fuster V, Friedrich JO (2013) Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol 1(4):317–328. doi:10.1016/S2213-8587(13)70089-5

    Article  PubMed  Google Scholar 

  32. Dangas GD, Farkouh ME, Sleeper LA, Yang M, Schoos MM, Macaya C, Abizaid A, Buller CE, Devlin G, Rodriguez AE, Lansky AJ, Siami FS, Domanski M, Fuster V, Investigators F (2014) Long-term outcome of PCI versus CABG in insulin and non-insulin-treated diabetic patients: results from the FREEDOM trial. J Am Coll Cardiol 64(12):1189–1197. doi:10.1016/j.jacc.2014.06.1182

    Article  CAS  PubMed  Google Scholar 

  33. Patterson C, Mapera S, Li HH, Madamanchi N, Hilliard E, Lineberger R, Herrmann R, Charles P (2006) Comparative effects of paclitaxel and rapamycin on smooth muscle migration and survival: role of AKT-dependent signaling. Arterioscler Thromb Vasc Biol 26(7):1473–1480. doi:10.1161/01.ATV.0000223866.42883.3b

    Article  CAS  PubMed  Google Scholar 

  34. Stone GW, Kedhi E, Kereiakes DJ, Parise H, Fahy M, Serruys PW, Smits PC (2011) Differential clinical responses to everolimus-eluting and Paclitaxel-eluting coronary stents in patients with and without diabetes mellitus. Circulation 124(8):893–900. doi:10.1161/CIRCULATIONAHA.111.031070

    Article  CAS  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany

      Salvatore Cassese, Sebastian Kufner, Erion Xhepa, Robert A. Byrne, Johanna Kreutzer, Massimiliano Fusaro, Heribert Schunkert & Adnan Kastrati

    2. 1. medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Lazarettstrasse 36, 80636, Munich, Germany

      Tareq Ibrahim & Karl-Ludwig Laugwitz

    3. Department of Cardiology, Helios Klinikum Wuppertal, Universität Witten/Herdecke, Wuppertal, Germany

      Klaus Tiroch

    4. Department of Cardiology, Bern University Hospital, Bern, Switzerland

      Marco Valgimigli

    5. Herzzentrum der Segeberger Kliniken Gruppe, Bad Segeberg, Germany

      Ralph Tölg

    6. Department of Cardiology, Ludwig-Maximilians-Universität, Munich, Germany

      Julinda Mehilli

    7. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany

      Heribert Schunkert, Karl-Ludwig Laugwitz, Julinda Mehilli & Adnan Kastrati

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    1. Salvatore Cassese
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    Correspondence to Sebastian Kufner.

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    RAB reports receiving lecture fees from B. Braun, Biotronik and Boston Scientific. The other authors declare no conflicts of interest.

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    For the Intracoronary Stenting and Angiographic Results: Drug-Eluting Stents for Unprotected Coronary Left Main Lesions (ISAR-LEFT MAIN) and ISAR-LEFT MAIN 2 Study Investigators.

    S. Cassese and S. Kufner contributed equally to this work.

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    Cassese, S., Kufner, S., Xhepa, E. et al. Three-year efficacy and safety of new- versus early-generation drug-eluting stents for unprotected left main coronary artery disease insights from the ISAR-LEFT MAIN and ISAR-LEFT MAIN 2 trials. Clin Res Cardiol 105, 575–584 (2016). https://doi.org/10.1007/s00392-015-0953-x

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