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Meta-Analysis of the Duration of Dual Antiplatelet Therapy in Patients Treated With Second-Generation Drug-Eluting Stents

      The purpose of the study was to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention, especially in the era of second-generation drug-eluting stents (DES). The work was conducted from November 2014 to April 2015. All randomized controlled trials comparing short (<12 months) versus long (≥12 months) DAPT in patients treated with second-generation DES were analyzed. Sensitivity analyses were performed for length of DAPT and type of DES. All-cause death was the primary end point, whereas cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), and major bleeding were secondary end points. Results were pooled and compared with random-effect models and meta-regression analysis. Eight randomized controlled trials with 18,810 randomized patients were included. The studies compared 3 versus 12 months of DAPT (2 trials), 6 versus 12 months (3 trials), 6 versus 24 months (1 trial), 12 versus 24 months (1 trial), and 12 versus 30 months (1 trial). Comparing short versus long DAPT, there were no significant differences in all-cause death (odds ratio [OR] 0.87; 95% confidence interval [CI] 0.66 to 1.44), cardiovascular death (OR 0.95; 95% CI 0.65 to 1.37), and ST (OR 1.20; 95% CI 0.79 to 1.83), and no differences were present when considering everolimus-eluting and fast-release zotarolimus-eluting stents separately. Shorter DAPT was inferior to longer DAPT in preventing MI (OR 1.35; 95% CI 1.03 to 1.77). Conversely, major bleeding was reduced by shorter DAPT (OR 0.60; 95% CI 0.42 to 0.96). Baseline features did not influence these results in meta-regression analysis. In conclusion, DAPT for ≤6 months is reasonable for patients treated with everolimus-eluting and fast-release zotarolimus-eluting stents, with the benefit of less major bleeding at the cost of increased MI, with similar survival and ST rates. An individualized patient approach to DAPT duration should take into account the competing risks of bleeding and ischemic complications after present-generation DES.
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      References

        • Sarno G.
        • Lagerqvist B.
        • Nilsson J.
        • Frobert O.
        • Hambraeus K.
        • Varenhorst C.
        • Jensen U.J.
        • Tödt T.
        • Götberg M.
        • James S.K.
        Stent thrombosis in new-generation drug-eluting stents in patients with STEMI undergoing primary PCI: a report from SCAAR.
        J Am Coll Cardiol. 2014; 64: 16-24
        • Palmerini T.
        • Biondi-Zoccai G.
        • Della Riva D.
        • Stettler C.
        • Sangiorgi D.
        • D'Ascenzo F.
        • Kimura T.
        • Briguori C.
        • Sabatè M.
        • Kim H.S.
        • De Waha A.
        • Kedhi E.
        • Smits P.C.
        • Kaiser C.
        • Sardella G.
        • Marullo A.
        • Kirtane A.J.
        • Leon M.B.
        • Stone G.W.
        Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.
        Lancet. 2012; 379: 1393-1402
        • D'Ascenzo F.
        • Bollati M.
        • Clementi F.
        • Castagno D.
        • Lagerqvist B.
        • de la Torre Hernandez J.M.
        • ten Berg J.M.
        • Brodie B.R.
        • Urban P.
        • Jensen L.O.
        • Sardi G.
        • Waksman R.
        • Lasala J.M.
        • Schulz S.
        • Stone G.W.
        • Airoldi F.
        • Colombo A.
        • Lemesle G.
        • Applegate R.J.
        • Buonamici P.
        • Kirtane A.J.
        • Undas A.
        • Sheiban I.
        • Gaita F.
        • Sangiorgi G.
        • Modena M.G.
        • Frati G.
        • Biondi-Zoccai G.
        Incidence and predictors of coronary stent thrombosis: evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses.
        Int J Cardiol. 2013; 167: 575-584
        • D'Ascenzo F.
        • Colombo F.
        • Barbero U.
        • Moretti C.
        • Omedè P.
        • Reed M.J.
        • Tarantini G.
        • Frati G.
        • Di Nicolantonio J.J.
        • Biondi Zoccai G.
        • Gaita F.
        Discontinuation of dual antiplatelet therapy over 12 months after acute coronary syndromes increases risk for adverse events in patients treated with percutaneous coronary intervention: systematic review and meta-analysis.
        J Interv Cardiol. 2014; 27: 233-241
        • Rossini R.
        • Musumeci G.
        • Visconti L.O.
        • Bramucci E.
        • Castiglioni B.
        • De Servi S.
        • Lettieri C.
        • Lettino M.
        • Piccaluga E.
        • Savonitto S.
        • Trabattoni D.
        • Capodanno D.
        • Buffoli F.
        • Parolari A.
        • Dionigi G.
        • Boni L.
        • Biglioli F.
        • Valdatta L.
        • Droghetti A.
        • Bozzani A.
        • Setacci C.
        • Ravelli P.
        • Crescini C.
        • Staurenghi G.
        • Scarone P.
        • Francetti L.
        • D'Angelo F.
        • Gadda F.
        • Comel A.
        • Salvi L.
        • Lorini L.
        • Antonelli M.
        • Bovenzi F.
        • Cremonesi A.
        • Angiolillo D.J.
        • Guagliumi G.
        Perioperative management of antiplatelet therapy in patients with coronary stents undergoing cardiac and non-cardiac surgery: a consensus document from Italian Cardiological, Surgical and Anaesthesiological Societies.
        EuroIntervention. 2014; 10: 38-46
        • Gada H.
        • Kirtane A.J.
        • Newman W.
        • Sanz M.
        • Hermiller J.B.
        • Mahaffey K.W.
        • Cutlip D.E.
        • Sudhir K.
        • Hou L.
        • Koo K.
        • Stone G.W.
        5-Year Results of a randomized comparison of XIENCE V everolimus-eluting and TAXUS paclitaxel-eluting stents: final results from the SPIRIT III trial (clinical evaluation of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo native coronary artery lesions).
        JACC Cardiovasc Interv. 2013; 6: 1263-1266
        • Giustino G.
        • Barber U.
        • Sartori S.
        • Meharn R.
        • Mastoris I.
        • Kini A.S.
        • Sharma S.K.
        • Pocock S.J.
        • Dangas G.D.
        Duration of dual antiplatelet therapy following drug-eluting stent implantation: a systematic review and meta-analysis of randomized controlled trials.
        J Am Coll Cardiol. 2015; 65: 1298-1310
        • Palmerini T.
        • Benedetto U.
        • Bacchi-Reggiani L.
        • Della Riva D.
        • Biondi-Zoccai G.
        • Feres F.
        • Abizaid A.
        • Hong M.K.
        • Kim B.K.
        • Jang Y.
        • Kim H.S.
        • Park K.W.
        • Genereux P.
        • Bhatt D.L.
        • Orlandi C.
        • De Servi S.
        • Petrou M.
        • Rapezzi C.
        • Stone G.W.
        Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials.
        Lancet. 2015; 385: 2371-2382
        • Palmerini T.
        • Stone G.W.
        Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: conceptual evolution based on emerging evidence.
        Eur Heart J. 2016; 37: 353-364
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman G.D.
        • for The PRISM Group
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        PLoS Med. 2009; 6: e1000097
        • D'Ascenzo F.
        • Biondi-Zoccai G.
        Network meta-analyses: the “white whale” for cardiovascular specialists.
        J Cardiothorac Vasc Anesth. 2014; 28: 169-173
        • Collet J.P.
        • Silvain J.
        • Barthélmy O.
        • Rangé G.
        • Cayla G.
        • Van Belle E.
        • Cuisset T.
        • Elhadad S.
        • Schiele F.
        • Lhoest N.
        • Ohlmann P.
        • Carrié D.
        • Rousseau H.
        • Aubry P.
        • Monségu J.
        • Sabouret P.
        • O'Connor S.A.
        • Abtan J.
        • Kerneis M.
        • Saint-Etienne C.
        • Beygui F.
        • Vicaut E.
        • Montalescot G.
        Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial.
        Lancet. 2014; 384: 1577-1585
        • Schulz-Schüpke S.
        • Byrne R.A.
        • Ten Berg J.M.
        • Neumann F.J.
        • Han Y.
        • Adriaenssens T.
        • Tölg R.
        • Seyfarth M.
        • Maeng M.
        • Zrenner B.
        • Jacobshagen C.
        • Mudra H.
        • Von Hodenberg E.
        • Wöhrle J.
        • Angiolillo D.J.
        • Von Merzljak B.
        • Rifatov N.
        • Kufner S.
        • Morath T.
        • Feuchtenberger A.
        • Ibrahim T.
        • Janssen P.W.
        • Valina C.
        • Li Y.
        • Desmet W.
        • Abdel-Wahab M.
        • Tiroch K.
        • Hengstenberg C.
        • Bernlochner I.
        • Fischer M.
        • Schunkert H.
        • Laugwitz K.L.
        • Schömig A.
        • Mehilli J.
        • Kastrati A.
        ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting.
        Eur Heart J. 2015; 36: 1252-1263
        • Colombo A.
        • Chieffo A.
        • Frasheri A.
        • Garbo G.
        • Massotti-Centol M.
        • Salvatella N.
        • Oteo Dominguez J.F.
        • Steffanon L.
        • Tarantini G.
        • Presbitero P.
        • Menozzi A.
        • Pucci E.
        • Mauri J.
        • Cesana B.M.
        • Giustino G.
        • Sardella G.
        Second-generation drug-eluting stent implantation followed by 6- versus 12-Month dual antiplatelet therapy: the SECURITY randomized clinical trial.
        J Am Coll Cardiol. 2014; 64: 2086-2097
        • Feres F.
        • Costa R.A.
        • Abizaid A.
        • Leon M.B.
        • Marin-Neto J.A.
        • Botelho R.V.
        • King S.B.
        • Negoita M.
        • Liu M.
        • de Paula J.E.
        • Mangione J.A.
        • Meireles G.X.
        • Castello Jr., H.J.
        • Nicolela Jr., E.L.
        • Perin M.A.
        • Devito F.S.
        • Labrunie A.
        • Salvadori Jr., D.
        • Gusmão M.
        • Staico R.
        • Costa Jr., J.R.
        • de Castro J.P.
        • Abizaid A.S.
        • Bhatt D.L.
        Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial.
        JAMA. 2013; 310: 2510-2522
        • Lee C.W.
        • Ahn J.M.
        • Park D.W.
        • Kang S.J.
        • Lee S.W.
        • Kim Y.H.
        • Park S.W.
        • Han S.
        • Lee S.G.
        • Seong I.W.
        • Rha S.W.
        • Jeong M.H.
        • Lim D.S.
        • Yoon J.H.
        • Hur S.H.
        • Choi Y.S.
        • Yang J.Y.
        • Lee N.H.
        • Kim H.S.
        • Lee B.K.
        • Kim K.S.
        • Lee S.U.
        • Chae J.K.
        • Cheong S.S.
        • Suh I.W.
        • Park H.S.
        • Nah D.Y.
        • Jeon D.S.
        • Seung K.B.
        • Lee K.
        • Jang J.S.
        • Park S.J.
        Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial.
        Circulation. 2014; 129: 304-312
        • Kim B.K.
        • Hong M.K.
        • Shin D.H.
        • Nam C.M.
        • Kim J.S.
        • Ko Y.G.
        • Choi D.
        • Kang T.S.
        • Park B.E.
        • Kang W.C.
        • Lee S.H.
        • Yoon J.H.
        • Hong B.K.
        • Kwon H.M.
        • Jang Y.
        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
        • Gwon H.C.
        • Hahn J.Y.
        • Park K.W.
        • Song Y.B.
        • Chae I.H.
        • Lim D.S.
        • Han K.R.
        • Choi J.H.
        • Choi S.H.
        • Kang H.J.
        • Koo B.K.
        • Ahn T.
        • Yoon J.H.
        • Jeong M.H.
        • Hong T.J.
        • Chung W.Y.
        • Choi Y.J.
        • Hur S.H.
        • Kwon H.M.
        • Jeon D.W.
        • Kim B.O.
        • Park S.H.
        • Lee N.H.
        • Jeon H.K.
        • Jang Y.
        • Kim H.S.
        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
        • Valgimigli M.
        • Borghesi M.
        • Tebaldi M.
        • Vranckx P.
        • Parrinello G.
        • Ferrari R.
        Should duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A pre-specified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY).
        Eur Heart J. 2013; 34: 909-919
        • Mauri L.
        • Kereiakes D.J.
        • Yeh R.W.
        • Driscoll-Shempp P.
        • Cutlip D.E.
        • Steg P.G.
        • Normand S.L.
        • Braunwald E.
        • Wiviott S.D.
        • Cohen D.J.
        • Holmes Jr., D.R.
        • Krucoff M.W.
        • Hermiller J.
        • Dauerman H.L.
        • Simon D.I.
        • Kandzari D.E.
        • Garratt K.N.
        • Lee D.P.
        • Pow T.K.
        • Ver Lee P.
        • Rinaldi M.J.
        • Massaro J.M.
        Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.
        N Engl J Med. 2014; 371: 2155-2166
        • Gilard M.
        • Barragan P.
        • Noryani A.A.
        • Noor H.A.
        • Majwal T.
        • Hovasse T.
        • Castellant P.
        • Schneeberger M.
        • Maillard L.
        • Bressolette E.
        • 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 K.
        • Benamer H.
        • Kiss R.G.
        • Ungi I.
        • Boschat J.
        • Morice M.C.
        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. 2015; 65: 777-786
        • Levine G.N.
        • Bates E.R.
        • Blankenship J.C.
        • Bailey S.R.
        • Bittl J.A.
        • Cercek B.
        • Chambers C.E.
        • Ellis S.G.
        • Guyton R.A.
        • Hollenberg S.M.
        • Khot U.N.
        • Lange R.A.
        • Mauri L.
        • Mehran R.
        • Moussa I.D.
        • Mukherjee D.
        • Nallamothu B.K.
        • Ting H.H.
        2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report 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-e122
        • Windecker S.
        • Kolh P.
        • Alfonso F.
        • Collet J.P.
        • Cremer J.
        • Falk V.
        • Filippatos G.
        • Hamm C.
        • Head S.J.
        • Jüni P.
        • Kappetein A.P.
        • Kastrati A.
        • Knuuti J.
        • Landmesser U.
        • Laufer G.
        • Neumann F.J.
        • Richter D.J.
        • Schauerte P.
        • Sousa Uva M.
        • Stefanini G.G.
        • Taggart D.P.
        • Torracca L.
        • Valgimigli M.
        • Wijns W.
        • Witkowski A.
        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
        • El-Hayek G.
        • Messerli F.
        • Bangalore S.
        • Hong M.K.
        • Herzog E.
        • Benjo A.
        • Tamis-Holland J.E.
        Meta-analysis of randomized clinical trials comparing short-term versus long-term dual antiplatelet therapy following drug-eluting stents.
        Am J Cardiol. 2014; 114: 236-242
        • Stone G.W.
        • Maehara A.
        • Lansky A.J.
        • de Bruyne B.
        • Cristea E.
        • Mintz G.S.
        • Mehran R.
        • McPherson J.
        • Farhat N.
        • Marso S.P.
        • Parise H.
        • Templin B.
        • White R.
        • Zhang Z.
        • Serruys P.W.
        A prospective natural-history study of coronary atherosclerosis.
        N Engl J Med. 2011; 364: 226-235
        • Iannaccone M.
        • Quadri G.
        • Taha S.
        • D'Ascenzo F.
        • Montefusco A.
        • Omede' P.
        • Jang I.K.
        • Niccoli G.
        • Souteyrand G.
        • Yundai C.
        • Toutouzas K.
        • Benedetto S.
        • Barbero U.
        • Annone U.
        • Lonni E.
        • Imori Y.
        • Biondi-Zoccai G.
        • Templin C.
        • Moretti C.
        • Luscher T.F.
        • Gaita F.
        Prevalence and predictors of culprit plaque rupture at OCT in patients with coronary artery disease: a meta-analysis.
        Eur Heart J Cardiovasc Imaging. 2015; ([Epub ahead of print])
        • Scirica B.M.
        • Bonaca M.P.
        • Braunwald E.
        • De Ferrari G.M.
        • Isaza D.
        • Lewis B.S.
        • Mehrhof F.
        • Merlini P.A.
        • Murphy S.A.
        • Sabatine M.S.
        • Tendera M.
        • Van de Werf F.
        • Wilcox R.
        • Morrow D.A.
        Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial.
        Lancet. 2012; 380: 1317-1324
        • D'Ascenzo F.
        • Taha S.
        • Moretti C.
        • Omedè P.
        • Grossomarra W.
        • Persson J.
        • Lamberts M.
        • Dewilde W.
        • Rubboli A.
        • Fernández S.
        • Cerrato E.
        • Meynet I.
        • Ballocca F.
        • Barbero U.
        • Quadri G.
        • Giordana F.
        • Conrotto F.
        • Capodanno D.
        • DiNicolantonio J.
        • Bangalore S.
        • Reed M.
        • Meier P.
        • Zoccai G.
        • Gaita F.
        Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin and oral anti-coagulants in patients undergoing percutaneous coronary intervention.
        Am J Cardiol. 2015; 115: 1185-1193
        • Vranckx P.
        • Leonardi S.
        • Tebaldi M.
        • Biscaglia S.
        • Parrinello G.
        • Rao S.V.
        • Mehran R.
        • Valgimigli M.
        Prospective validation of the bleeding Academic Research Consortium classification in the all-comer PRODIGY trial.
        Eur Heart J. 2014; 35: 2524-2529
        • Bianco M.
        • Bernardi A.
        • D'Ascenzo F.
        • Cerrato E.
        • Omedè P.
        • Montefusco A.
        • DiNicolantonio J.J.
        • Zoccai G.B.
        • Varbella F.
        • Carini G.
        • Moretti C.
        • Pozzi R.
        • Gaita F.
        Efficacy and safety of available protocols for aspirin hypersensitivity for patients undergoing percutaneous coronary intervention: a survey and systematic review.
        Circ Cardiovasc Interv. 2016; 9: e002896