Efficacy and safety of 12 versus 48 months of dual antiplatelet therapy after implantation of a drug-eluting stent: the OPTImal DUAL antiplatelet therapy (OPTIDUAL) trial: study protocol for a randomized controlled trial

Trials

Jean-Philippe Metzger⁴  Eric Vicaut⁸  Guillaume Cayla⁷  Simon Cattan⁵  Laurent Sebagh²  Fabrice Prunier⁹  Alain Furber⁹  Hélène Eltchaninoff³  Florence Leclercq¹  Didier Carrie⁶  Jean Louis Georges^1,10  Claude Le Feuvre⁴  Gérard Helft⁴ 

[1] avenue du Doyen Gaston Giraud Hôpital CHU, Montpellier, France;rue de Turin Clinique Turin, Paris, France;rue de Germont, CHU, Rouen, France;bd Vincent Auriol, Institut de Cardiologie, Hôpital Pitié-Salpétrière, Paris, France;10, rue du Général Leclerc, Hôpital Le Raincy, Le Raincy, France;avenue Jean Poulhes, CHU, Toulouse, France;place du Pr-Debré GHU, Carémeau, Nîmes, France;rue du Faubourg St Denis URC Hôpital, Lariboisière, Paris, France;rue Larrey, CHU, Angers, France;rue de Versailles Hôpital Mignot, Versailles, France

关键词: Randomized clinical trial;    Stent thrombosis;    Coronary artery disease;    Clopidogrel;    Drug-eluting stent;   

Others  :  1094675
DOI  :  10.1186/1745-6215-14-56

 received in 2012-10-05, accepted in 2013-02-11,  发布年份 2013

【 摘 要 】

Background

Dual antiplatelet therapy with aspirin and thienopyridine is required after placement of coronary drug-eluting stents (DES) to prevent thrombotic complications. Current clinical guidelines recommend at least 6 to 12 months of treatment after a DES implantation, but it may be beneficial to apply dual antiplatelet therapy for a longer duration.

Methods/design

The optimal dual antiplatelet therapy (OPTIDUAL) study aims to compare the benefits and risks of dual antiplatelet therapy applied for either 12 or 48 months. We will examine the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention with DES for the treatment of coronary lesions. The OPTIDUAL study is an open-label multicenter, randomized, national trial that will include 1,966 patients treated with DES. All patients will be treated with dual antiplatelet therapy for 12 months (+/− 3). Then, patients with no MACCE or major bleeding will be randomized to receive either 36 additional months of clopidogrel plus aspirin or aspirin only. The primary end-point is the combination of death from all causes, myocardial infarction, stroke and major bleeding. The secondary end points include the individual components of the primary end-point, stent thrombosis, repeat revascularization of the treated vessel and minor bleeding.

Discussion

This randomized trial is designed to assess the benefits and safety of 12 versus 48 months of dual antiplatelet therapy in patients that receive a DES. We aim to determine whether substantial prolongation of clopidogrel (a thienopyridine) after DES implantation offers an advantage over its discontinuation.

Trial registration

ClinicalTrials.gov Identifier: NCT00822536

【 授权许可】

   
2013 Helft et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH: Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 2000, 102:624-629.
• [2]Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK: Clopidogrel in unstable angina to prevent recurrent Events trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-elevation. N Engl J Med 2001, 345:494-502.
• [3]Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA: Clopidogrel in unstable angina to prevent recurrent events trial (CURE) investigators. Effects of pre-treatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001, 358:527-533.
• [4]Steinbuhl SR, Berger PB, Mann JT III, Fry RT, Wilmer C, Topol EJ, CREDO Investigators: Clopidogrel for the reduction of events during observation (CREDO) investigators. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002, 288:2411-2420.
• [5]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: Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003, 349:1315-1323.
• [6]Stone GW, Elis 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: a polymer-based, placlitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004, 350:221-231.
• [7]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: Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting stent versus bare metal stents. J Am Coll Cardiol 2006, 48:2584-2591.
• [8]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: Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 2007, 297:159-168.
• [9]Park DW, Park SW, Park KH, Lee BK, Kim YH, Lee CW, Hong MK, Kim JJ, Park SJ: Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol 2006, 98:352-356.
• [10]Nair R, Simon DI: Antiplatelet therapy in the era of late stent thrombosis. Curr Treat Options Cardiovasc Med 2008, 10:12-17.
• [11]Ho PM, Fihn SD, Wang L, Bryson CL, Lowy E, Maynard C, Magid DJ, Peterson ED, Jesse RL, Rumsfeld JS: Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome. Am Heart J 2007, 154:846-851.
• [12]Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS, Messenger JC, Khanal S, Peterson ED, Bach RG, Krumholz HM, Cohen DJ: Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006, 113:2803-2809.
• [13]Artang R, Dieter RS: Analysis of 36 reported cases of late thrombosis in drug-eluting stents placed in coronary arteries. Am J Cardiol 2007, 99:1039-1043.
• [14]King SB III, Smith SC Jr, Hirshfeld JW Jr, Jacobs AK, Morrison DA, Williams DO, Feldman TE, Kern MJ, O'Neill WW, Schaff HV, Whitlow PL, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Page RL, Riegel B, Tarkington LG, Yancy CW, 2005 Writing Committee Members: Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to review new evidence and update the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention. Writing on behalf of the 2005 Writing Committee. Circulation 2008, 117:261-295. Erratum in Circulation 2008, 117:e161
• [15]Silber S, Albertsson P, Aviles FF, Camici PG, Colombo A, Hamm C, Jørgensen E, Marco J, Nordrehaug JE, Ruzyllo W, Urban P, Stone GW, Wijns W: Guidelines for percutaneous coronary interventions. The task force for percutaneous coronary interventions of the European Society of Cardiology. Eur Heart J 2005, 26:804-847.
• [16]Ho PM, Peterson ED, Wang L, Magid DJ, Fihn SD, Larsen GC, Jesse RA, Rumsfeld JS: Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. JAMA 2008, 299:532-539.
• [17]CAPRIE Steering Committee: A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996, 348:1329-1339.
• [18]Bowry AD, Brookhart MA, Choudhry NK: Meta-analysis of the efficacy and safety of clopidogrel as compared to antiplatelet monotherapy for the prevention of vascular events. Am J Cardiol 2008, 101:960-966.
• [19]Park SJ, Park DW, Kim YH, Kang SJ, Lee SW, Lee CW, Han KH, Park SW, Yun SC, Lee SG, Rha SW, Seong IW, Jeong MH, Hur SH, Lee NH, Yoon J, Yang JY, Lee BK, Choi YJ, Chung WS, Lim DS, Cheong SS, Kim KS, Chae JK, Nah DY, Jeon DS, Seung KB, Jang JS, Park HS, Lee K: Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 2010, 362:1374-1382.
• [20]Gwon HC, Hahn JY, Park KW, Song YB, Chae IH, Lim DS, Han KR, Choi JH, Choi SH, Kang HJ, Koo BK, Ahn T, Yoon JH, Jeong MH, Hong TJ, Chung WY, Choi YJ, Hur SH, Kwon HM, Jeon DW, Kim BO, Park SH, Lee NH, Jeon HK, Jang Y, Kim HS: Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus versus Cypher to Reduce Late Loss after Stenting (EXCELLENT) randomized, multicenter study. Circulation 2012, 24:505-513.
• [21]Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F, Tebaldi M, Fucà G, Kubbajeh M, Cangiano E, Minarelli M, Scalone A, Cavazza C, Frangione A, Borghesi M, Marchesini J, Parrinello G, Ferrari R, Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) Investigators: Short- versus long-term duration of dual antiplatelet therapy after coronary stenting. A randomized multicenter trial. Circulation 2012, 125:2015-2026.
• [22]Campbell CL, Smyth S, Montalescot G, Steinhubl SR: Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA 2007, 297:2018-2024.
• [23]Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, Faxon DP, Rupprecht HJ, Budaj A, Avezum A, Widimsky P, Steg PG, Bassand JP, Montalescot G, Macaya C, Di Pasquale G, Niemela K, Ajani AE, White HD, Chrolavicius S, Gao P, Fox KA, Yusuf S, CURRENT-OASIS 7 trial investigators: Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (Current-Oasis 7): a randomised factorial trial. Lancet 2010, 376:1233-1243.
• [24]Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW, Academic Research Consortium: Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007, 115:2344-2351.
• [25]Lakatos E, Lan KK: A comparison of sample size methods for the logrank statistics. Stat Med 1992, 11:179-191.
• [26]Proschan MA, Liu Q, Hunsberger S: Practical midcourse sample size modifications in clinical trials. Contr Clin Trials 2003, 24:4-15.
• [27]Mauri L, Kereiaked DJ, Normand SL, Wiviott SD, Cohen DJ, Holmes DR, Bangalore S, Cutlip DE, Pencina M, Massaro JM: Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent or baremetal stent placement for the treatment of coronary artery lesions. Am Heart J 2010, 160:1035-1041.
• [28]Byrne RA, Schulz S, Mehilli J, Iijima R, Massberg S, Neumann FJ, ten Berg JM, Schömig A, Kastrati A, Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of Six Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) Investigators: Rationale and design of a randomized, double-blind, placebo-controlled trial of 6 versus 12 months clopidogrel therapy after implantation of a drug-eluting stent: The Intracoronary Stenting and Antithrombotic Regimen: Safety and Efficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) study. Am Heart J 2009, 157:620-624.