Skip to main content
Log in

Impact of duration of clopidogrel prescription on outcome of DES as compared to BMS in primary angioplasty: a meta-regression analysis of randomized trials

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Aims Recent concerns have emerged on the potential higher risk of stent thrombosis after Drug-eluting stents (DES) implantation, that might be even more pronounced among ST-segment elevation myocardial infarction (STEMI) patients. The aim of the current study was to evaluate, by a meta-analytic approach, whether the benefits and safety of DES as compared to bare-metal stents (BMS) in patients undergoing primary angioplasty for STEMI may be influenced by the duration of prescription of dual oral antiplatelet therapy. Methods The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. Results A total of 12 trials were included in the meta-analysis, involving 4,351 patients (2,260 or 51.9% randomized to DES and 2,091 or 48.1% randomized to BMS). In five trials (involving 1690 patients) dual oral antiplatelet therapy was prescribed for at least 1 year. The outcome of DES as compared to BMS was not affected by the duration of dual antiplatelet therapy in terms of death (P interaction = 0.16), reinfarction (P interaction = 0.91) and in-stent thrombosis (P interaction = 0.26) and TVR (P interaction = 0.38). These data were confirmed by the use of a meta-regression analysis. Conclusions This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, DES (SES and PES), as compared to BMS, are safe and their benefits are not affected by the duration of clopidogrel prescription.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Zijlstra F, Hoorntje JC, de Boer MJ, Reiffers S, Miedema K, Ottervanger JP, van ‘t Hof AW, Suryapranata H (1999) Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 341:1413–1419

    Article  PubMed  CAS  Google Scholar 

  2. Keeley EC, Boura JA, Grines CL (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361:13–20

    Article  PubMed  Google Scholar 

  3. Bhatt DL, Bertrand ME, Berger PB, L’Allier PL, Moussa I, Moses JW, Dangas G, Taniuchi M, Lasala JM, Holmes DR, Ellis SG, Topol EJ (2002) Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol 39:9–14

    Article  PubMed  CAS  Google Scholar 

  4. De Luca G, Suryapranata H, Stone GW, Antoniucci D, Tcheng JE, Neumann FJ, Van de Werf F, Antman EM, Topol EJ (2005) Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA 293:1759–1765

    Article  PubMed  Google Scholar 

  5. Zhu MM, Feit A, Chadow H, Alam M, Kwan T, Clark LT (2001) Primary stent implantation compared with primary balloon angioplasty for acute myocardial infarction: a meta-analysis of randomised clinical trials. Am J Cardiol 88:297–301

    Article  PubMed  CAS  Google Scholar 

  6. De Luca G, Suryapranata H, Stone GW, Antoniucci D, Biondi-Zoccai G, Kastrati A, Chiariello M, Marino P (2007) Coronary stenting versus balloon angioplasty for acute myocardial infarction: a meta-regression analysis of randomized trials. Int J Cardiol. Jun 1 [Epub ahead of print]

  7. Suryapranata H, De Luca G, van ‘t Hof AW, Ottervanger JP, Hoorntje JC, Dambrink JH, Gosselink AT, Zijlstra F, de Boer MJ (2005) Is routine stenting for acute myocardial infarction superior to balloon angioplasty? A randomized comparison in a large unselected cohort of patients. Heart 91:641–645

    Article  PubMed  CAS  Google Scholar 

  8. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE, SIRIUS Investigators (2003) Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 349:1315–23

    Google Scholar 

  9. Stone GW, Ellis SG, Cox DA, Hermiller J, O’Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenberg J, Popma JJ, Russell ME, TAXUS-IV Investigators (2004) A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 350:221–231

  10. Ardissino D, Cavallini C, Bramucci E, Indolfi C, Marzocchi A, Manari A, Angeloni G, Carosio G, Bonizzoni E, Colusso S, Repetto M, Merlini PA, SES-SMART Investigators (2004) Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial. JAMA 292:2727–2734

    Google Scholar 

  11. Colombo A, Moses JW, Morice MC, Ludwig J, Holmes DR Jr, Spanos V, Louvard Y, Desmedt B, Di Mario C, Leon MB (2004) Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation 109:1244–1249

    Article  PubMed  Google Scholar 

  12. Roiron C, Sanchez P, Bouzamondo A, Lechat P, Montalescot G (2006) Drug eluting stents: an updated meta-analysis of randomised controlled trials. Heart 92:641–649

    Article  PubMed  CAS  Google Scholar 

  13. McFadden EP, Stabile E, Regar E, Cheneau E, Ong AT, Kinnaird T, Suddath WO, Weissman NJ, Torguson R, Kent KM, Pichard AD, Satler LF, Waksman R, Serruys PW (2004) Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 364:1519–1521

    Article  PubMed  CAS  Google Scholar 

  14. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A (2005) Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 293:2126–2130

    Article  PubMed  CAS  Google Scholar 

  15. Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS, Messenger JC, Khanal S, Peterson ED, Bach RG, Krumholz HM, Cohen DJ (2006) Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 113:2803–2809

    Article  PubMed  CAS  Google Scholar 

  16. Kernis SJ, Cohen D, Rein K (2005) Clinical outcome associated with use of drug-eluting stents compared with bare metal stent for primary percutaneous intervention. Am J Cardiol 96(Suppl 7A):47H

    Google Scholar 

  17. Daemen J, Tanimoto S, García-García HM, Kukreja N, van de Sande M, Sianos G, de Jaegere PP, van Domburg RT, Serruys PW (2007) Comparison of three-year clinical outcome of sirolimus- and paclitaxel-eluting stents versus bare metal stents in patients with ST-segment elevation myocardial infarction (from the RESEARCH and T-SEARCH Registries). Am J Cardiol 99:1027–1032

    Article  PubMed  CAS  Google Scholar 

  18. Egger M, Smith GD (1998) Bias in location and selection of studies. BMJ 31:61–66

    Google Scholar 

  19. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet 354:1896–1900

    Article  PubMed  CAS  Google Scholar 

  20. Valgimigli M, Bolognese L, Anselmi M, Campo G, Rodriguez AE, de Cesare N, Cohen DJ, Sheiban I, Colangelo S, Pasquetto G, Hamon M, Vranckx P, Ferrario M, Prati F, Agostoni P, Malagutti P, Arcozzi C, Parrinello G, Vassanelli C, Ferrari R, Percoco G (2005) Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial. JAMA 293:2109–2117

    Article  PubMed  Google Scholar 

  21. Laarman GJ, Suttorp MJ, Dirksen MT, van Heerebeek L, Kiemeneij F, Slagboom T, van der Wieken LR, Tijssen JG, Rensing BJ, Patterson M (2006) Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. N Engl J Med 355:1105–1113

    Article  PubMed  CAS  Google Scholar 

  22. Spaulding C, Henry P, Teiger E, Beatt K, Bramucci E, Carrié D, Slama MS, Merkely B, Erglis A, Margheri M, Varenne O, Cebrian A, Stoll HP, Snead DB, Bode C, TYPHOON Investigators (2006) Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med 355:1093–1104

    Google Scholar 

  23. Di Lorenzo E, Varricchio A, Lanzillo T (2005) Paclitaxel and Sirolimus stent implantation in patients with acute myocardial infarction. Circulation 112(Abstract Suppl):II–478

    Google Scholar 

  24. Menichelli M, Parma A, Pucci E, Fiorilli R, De Felice F, Nazzaro M, Giulivi A, Alborino D, Azzellino A, Violini R (2007) Randomized trial of sirolimus-eluting stent versus bare-metal stent in acute myocardial infarction (SESAMI). J Am Coll Cardiol 49:1924–1930

    Article  PubMed  CAS  Google Scholar 

  25. Pittl U, Kaiser C, Brunner-La Rocca HP (2006) BASKET Investigators. Safety and efficacy of drug eluting stents versus bare metal stents in primary angioplasty of patients with acute ST-elevation myocardial infarction—a prospective randomized study. Eur Heart J 27(Abstract Suppl):650

    Google Scholar 

  26. Sardella G, Paroli M, Mancone M (2006) Impact of paclitaxel-eluting stent implantation in patients with STEMI on anti-inflammatory IL-10-producing T regulatory 1 (Tr1) cells. Eur Heart J 27(Abstract Suppl):831

    Google Scholar 

  27. Pasceri V, Granatelli A, Pristipino C (2003) A randomized trial of a rapamycin-eluting stent in acute myocardial infarction: preliminary results. Am J Cardiol 92(Suppl 6A):1L

    Google Scholar 

  28. Tierala I. The Helsinki area acute myocardial infarction treatment re-evaluation—should the patient get a drug-eluting or a normal stent (HAAMU-STENT) study. http://www.tctmd.com/csportal/appmanager/tctmd/main?_nfpb=true&_pageLabel=TCTMDContent&hdCon=1453095. Accessed 5 March 2007

  29. A prospective randomized controlled trial to evaluate the efficacy of drug-eluting stents versus bare-metal stents for the treatment of acute myocardial infarction (MISSION trial). http://www.cardiosourcecom/clinicaltrials/browseAcronymasp?alpha=M. Accessed 5 March 2007

  30. Chechi T, Vittori G, Biondi Zoccai GG, Vecchio S, Falchetti E, Spaziani G, Baldereschi G, Giglioli C, Valente S, Margheri M (2007) Single-center randomized evaluation of paclitaxel-eluting versus conventional stent in acute myocardial infarction (SELECTION). J Interv Cardiol 20:282–291

    Article  PubMed  Google Scholar 

  31. Díaz de la Llera LS, Ballesteros S, Nevado J, Fernández M, Villa M, Sánchez A, Retegui G, García D, Martínez A (2007) Sirolimus-eluting stents compared with standard stents in the treatment of patients with primary angioplasty. Am Heart J 154(164):e1–6

  32. Kelbæk H, Thuesen L, Helqvist S. Prospective, randomized comparison of drug-eluting and bare metal stents in acute myocardial infarction: 8 months clinical and angiographic results. The drug elution and distal protection in ST-elevation myocardial infarction (DEDICATION) study. http://www.tctmd.com/csportal/appmanager/tctmd/main?_nfpb=true&_pageLabel=TCTMDContent&hdCon=1518197

  33. Karjalainen I. TITAX AMI trial. http://www.tctmd.com/csportal/appmanager/tctmd/tct2007?_nfpb=true&_pageLabel=TCT2007Content&hdCon=1518259. Accessed 5 March 2007

  34. Valgimigli M, Campo G, Percoco G, Bolognese L, Vassanelli C, Colangelo S, de Cesare N, Rodriguez AE, Ferrario M, Moreno R, Piva T, Sheiban I, Pasquetto G, Prati F, Nazzaro MS, Parrinello G, Ferrari R; for the Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs Abciximab With Sirolimus-Eluting Stent or Bare Metal Stent in Acute Myocardial Infarction Study (MULTISTRATEGY) Investigators. Comparison of angioplasty with infusion of Tirofiban or Abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: The MULTISTRATEGY Randomized Trial. JAMA. Mar 30 2008 [Epub ahead of print]

  35. De Luca G, Ernst N, van ‘t Hof AW, Ottervanger JP, Hoorntje JC, Gosselink AT, Dambrink JH, de Boer MJ, Suryapranata H (2006) Predictors and clinical implications of early reinfarction after primary angioplasty for ST-segment elevation myocardial infarction. Am Heart J 151:1256–1259

    Article  PubMed  Google Scholar 

  36. Kastrati A, Dibra A, Spaulding C, Laarman GJ, Menichelli M, Valgimigli M, Di Lorenzo E, Kaiser C, Tierala I, Mehilli J, Seyfarth M, Varenne O, Dirksen MT, Percoco G, Varricchio A, Pittl U, Syvänne M, Suttorp MJ, Violini R, Schömig A (2007) Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction. Eur Heart J 28:2706–2713

    Article  PubMed  Google Scholar 

  37. Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, Kramer JM, Harrington RA, Matchar DB, Kandzari DE, Peterson ED, Schulman KA, Califf RM (2007) Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 297:159–168

    Article  PubMed  CAS  Google Scholar 

  38. Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schömig A, Pfisterer ME, Stone GW, Leon MB, de Lezo JS, Goy JJ, Park SJ, Sabaté M, Suttorp MJ, Kelbaek H, Spaulding C, Menichelli M, Vermeersch P, Dirksen MT, Cervinka P, Petronio AS, Nordmann AJ, Diem P, Meier B, Zwahlen M, Reichenbach S, Trelle S, Windecker S, Jüni P (2007) Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet 370:937–948

    Article  PubMed  CAS  Google Scholar 

  39. Lagerqvist B, James SK, Stenestrand U, Lindbäck J, Nilsson T, Wallentin L, SCAAR Study Group (2007) Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med 356:1009–1019

    Google Scholar 

  40. Airoldi F, Colombo A, Morici N, Latib A, Cosgrave J, Buellesfeld L, Bonizzoni E, Carlino M, Gerckens U, Godino C, Melzi G, Michev I, Montorfano M, Sangiorgi GM, Qasim A, Chieffo A, Briguori C, Grube E (2007) Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment. Circulation 116:745–754

    Article  PubMed  CAS  Google Scholar 

  41. Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, Mueller C, Jeger R, Bader F, Osswald S, Kaiser C, BASKET-LATE Investigators (2006) 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 48:2584–2591

  42. Stone GW. Harmonizing outcomes with revascularization and stents in acute myocardial infarction. http://clinicaltrials.gov/ct/show/NCT004 33966?order=1. Accessed 5 March 2007

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giuseppe De Luca.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Luca, G., Cassetti, E. & Marino, P. Impact of duration of clopidogrel prescription on outcome of DES as compared to BMS in primary angioplasty: a meta-regression analysis of randomized trials. J Thromb Thrombolysis 27, 365–378 (2009). https://doi.org/10.1007/s11239-008-0223-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-008-0223-0

Keywords

Navigation