ISAR-SAFE: A randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting

European Heart Journal

Volumn 36, Issue 20, 2015, Pages 1252-1263

  Schulz Schüpke, Stefanie ^a,b   Byrne, Robert A ^a   Ten Berg, Jurrien M ^c   Neumann, Franz Josef ^d   Han, Yaling ^e   Adriaenssens, Tom ^f   Tölg, Ralph ^g   Seyfarth, Melchior ^h   Maeng, Michael ⁱ   Zrenner, Bernhard ^j   Jacobshagen, Claudius ^k   Mudra, Harald ^l   Von Hodenberg, Eberhard ^m   Wöhrle, Jochen ⁿ   Angiolillo, Dominick J ^o   Von Merzljak, Barbara ^a   Rifatov, Nonglag ^a   Kufner, Sebastian ^a   Morath, Tanja ^a   Feuchtenberger, Antonia ^a   Ibrahim, Tareq ^p   Janssen, Paul W A ^c   Valina, Christian ^d   Li, Yi ^e   Desmet, Walter ^f   Abdel Wahab, Mohamed ^g   Tiroch, Klaus ^h   Hengstenberg, Christian ^a,b   Bernlochner, Isabell ^p   Fischer, Marcus ^q   Schunkert, Heribert ^a,b   Laugwitz, Karl Ludwig ^b,p   Schömig, Albert ^a   Mehilli, Julinda ^b,r   Kastrati, Adnan ^a,b   more..

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

^c ST ANTONIUS HOSPITAL   (Netherlands)

^d UNIVERSITY HEART CENTER FREIBURG BAD KROZINGEN   (Germany)

^e SHENYANG NORTHERN HOSPITAL   (China)

^f UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^g Segeberger Kliniken Gruppe   (Germany)

^h UNIVERSITY OF WITTEN HERDECKE   (Germany)

ⁱ AARHUS UNIVERSITY HOSPITAL   (Denmark)

^j Krankenhaus Landshut Achdorf   (Germany)

^k UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^l Klinikum Neuperlach   (Germany)

^m Herzzentrum Lahr/Baden   (Germany)

ⁿ UNIVERSITY HOSPITAL ULM   (Germany)

^o UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^p TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^q UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^r LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

more..

Author keywords

Clopidogrel; Double blind; Drug eluting stent; Dual antiplatelet therapy; Randomized trial; Stent thrombosis

Indexed keywords

CLOPIDOGREL; PLACEBO; ANTITHROMBOCYTIC AGENT; TICLOPIDINE;

ADULT; AGED; ARTICLE; BLOOD CLOT LYSIS; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; DEATH; DOUBLE BLIND PROCEDURE; DRUG ELUTING STENT; FEMALE; HEART INFARCTION; HUMAN; HYPOTHESIS; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MULTICENTER STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; STENT THROMBOSIS; TREATMENT OUTCOME; ANALOGS AND DERIVATIVES; BLEEDING; CHEMICALLY INDUCED; CLINICAL TRIAL; COMPARATIVE STUDY; CORONARY ARTERY DISEASE; DRUG ADMINISTRATION; GRAFT OCCLUSION, VASCULAR; MORTALITY; MYOCARDIAL INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; PROCEDURES; PROSTHESIS FAILURE; STROKE;

AGED; CORONARY ARTERY DISEASE; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG-ELUTING STENTS; FEMALE; GRAFT OCCLUSION, VASCULAR; HEMORRHAGE; HUMANS; MALE; MIDDLE AGED; MYOCARDIAL INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; PLATELET AGGREGATION INHIBITORS; PROSTHESIS FAILURE; STROKE; TICLOPIDINE; TREATMENT OUTCOME;

EID: 84926332974     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehu523     Document Type: Article

References (29)

1. Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, RichardtG, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-Artery stents. N Engl J Med 1996; 334: 1084-1089
2. Byrne RA, Sarafoff N, Kastrati A, Schomig A. Drug-eluting stents in percutaneous coronary intervention: a benefit-risk assessment. Drug Saf 2009; 32: 749-770
3. Stefanini GG, HolmesDR Jr. Drug-eluting coronary-Artery stents.NEngl J Med 2013; 368: 254-265
4. Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007; 356: 998-1008
5. Kastrati A, Mehilli J, Pache J, Kaiser C, Valgimigli M, Kelbaek H, Menichelli M, Sabate M, Suttorp MJ, Baumgart D, Seyfarth M, Pfisterer ME, Schomig A. Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med 2007; 356: 1030-1039
6. 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, Authors/Task Force m. 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 2014; 35: 2541-2619
7. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH, American College of Cardiology F, American Heart Association Task Force on Practice G, Society for Cardiovascular A, Interventions. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention.Areport of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol 2011; 58: e44-122
8. 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
9. Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F, Tebaldi M, Fuca G, Kubbajeh M, Cangiano E, Minarelli M, Scalone A, Cavazza C, Frangione A, BorghesiM, Marchesini J, Parrinello G, Ferrari R, Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study I. Short- versus long-Term duration of dual-Antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation 2012; 125: 2015-2026
10. Kim BK, Hong MK, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Kang TS, Park BE, Kang WC, Lee SH, Yoon JH, Hong BK, Kwon HM, Jang Y, Investigators R. A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol 2012; 60: 1340-1348
11. Gwon HC, Hahn JY, ParkKW, Song YB, Chae IH, Lim DS, Han KR, Choi JH, Choi SH, Kang HJ, Koo BK, Ahn T, Yoon JH, Jeong MH, Hong TJ, ChungWY, Choi YJ, Hur SH, Kwon HM, JeonDW, Kim BO, ParkSH, 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; 125: 505-513
12. Feres F, Costa RA, Abizaid A, Leon MB, Marin-Neto JA, Botelho RV, King SB III, Negoita M, Liu M, De Paula JE, Mangione JA, Meireles GX, Castello HJ Jr, Nicolela EL Jr, Perin MA, Devito FS, Labrunie A, Salvadori D Jr, Gusmao M, Staico R, Costa JR Jr, De Castro JP, Abizaid AS, Bhatt DL, for the OTI. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA 2013; 310: 2510-2522
13. Colombo A, Chieffo A, Frasheri A, Garbo R, Masotti M, Salvatella N, Oteo Dominguez JF, Steffanon L, Tarantini G, Presbitero P, Menozzi A, Pucci E, Mauri J, Cesana BM, Giustino G, Sardella G. Second generation drug-eluting stents implantation followed by six versus twelve-month - dual antiplatelet therapy-The SECURITY Randomized Clinical Trial. J Am Coll Cardiol 2014; 64: 2086-2097
14. Cassese S, Byrne RA, Tada T, King LA, Kastrati A. Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-Analysis of randomized trials. Eur Heart J 2012; 33: 3078-3087
15. Collet JP, Silvain J, Barthelemy O, Range G, Cayla G, Van Belle E, Cuisset T, Elhadad S, Schiele F, Lhoest N, Ohlmann P, Carrie D, Rousseau H, Aubry P, Monsegu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Beygui F, Vicaut E, Montalescot G, for the Ai. Dual-Antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet 2014; 384: 1577-1585
16. Byrne RA, Schulz S, Mehilli J, Iijima R, Massberg S, Neumann FJ, ten Berg JM, Schomig A, Kastrati A. Rationale and design of a randomized, double-blind, placebocontrolled 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: 620-4 e2
17. Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007; 356: 1020-1029
18. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, KrucoffMW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123: 2736-2747
19. 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
20. HauckWW, Anderson S.A comparison of large sample confidence interval methods for the difference of two binomial probabilities. Am. Stat. 1986; 40: 318-322
21. Gilard M, Barragan P, Noryani AA, Noor HA, Majwal T, Hovasse T, Castellant P, Schneeberger M, Maillard L, Bressolette EE, Wojcik J, Delarche N, Blanchard D, Jouve B, Ormezzano O, Paganelli F, Levy G, Sainsous J, Carrie D, Furber A, Berland J, Darremont O, Le Breton H, Lyuycx-Bore A, Gommeaux A, Cassat C, Kermarrec A, Cazaux P, Druelles P, Dauphin R, Armengaud J, Dupouy P, Champagnac D, Ohlmann P, Endresen KK, Benamer H, Kiss RG, Ungi I, Boschat J, Morice MC. Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial. J Am Coll Cardiol 2014; doi: 10.1016/j.jacc.2014.11.008. [Epub ahead of print].
22. Raber L, Magro M, Stefanini GG, Kalesan B, Van Domburg RT, Onuma Y, Wenaweser P, Daemen J, Meier B, Juni P, Serruys PW, Windecker S. Very late coronary stent thrombosis of a newer-generation everolimus-eluting stent compared with early-generation drug-eluting stents: a prospective cohort study. Circulation 2012; 125: 1110-1121
23. 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. Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and secondgeneration drug-eluting stents: results from a registry of 18, 334 patients. JACC Cardiovasc Interv 2013; 6: 1267-1274
24. Ndrepepa G, Berger PB, Mehilli J, Seyfarth M, Neumann FJ, Schomig A, Kastrati A. Periprocedural bleeding and 1-yearoutcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 2008; 51: 690-697
25. Fiedler KA, Mehilli J, Kufner S, Schlichting A, Ibrahim T, Sibbing D, Ott I, Schunkert H, Laugwitz KL, Kastrati A, Schulz S. Randomised, double-blind trial on the value of tapered discontinuation of clopidogrel maintenance therapy after drug-eluting stent implantation. Intracoronary Stenting andAntithromboticRegimen: CAUTIONinDiscontinuing Clopidogrel Therapy-ISAR-CAUTION. Thromb Haemost 2014; 111: 1041-1049
26. Sibbing D, Stegherr J, Braun S, Mehilli J, Schulz S, Seyfarth M, Kastrati A, von Beckerath N, Schomig A. A double-blind, randomized study on prevention and existence of a rebound phenomenon of platelets after cessation of clopidogrel treatment. J Am Coll Cardiol 2010; 55: 558-565
27. Stefanini GG, Siontis GC, Cao D, Heg D, Juni P, Windecker S. Short versus long duration of DAPT after DES implantation: a meta-Analysis. J Am Coll Cardiol 2014; 64: 953-954
28. Ndrepepa G, Schuster T, Hadamitzky M, Byrne RA, Mehilli J, Neumann FJ, Richardt G, Schulz S, Laugwitz KL, Massberg S, Schomig A, Kastrati A. Validation of the Bleeding Academic Research Consortium definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention. Circulation 2012; 125: 1424-1431
29. Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr., Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Lee PV, Rinaldi MJ, Massaro JM, the DSI. Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents. N Engl J Med 2014; 371: 2155-2166