Optimal timepoint for the discontinuation of dual antiplatelet therapy (DAPT) after an acute coronary syndrome is still debated. In fact, despite a shortening of DAPT duration should be advocated, based on the negligible risk of thrombotic complications observed with newer generations of drug-eluting stents (DES), in order to reduce the hemorrhagic risk, a more prolonged anti-ischemic protection would be suitable for certain higher-risk patients, rendering the traditional 12 months strategy outdated. We performed an updated meta-analysis and indirect comparison of randomized trials comparing shorter vs extended DAPT duration in ACS patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched for studies comparing 3–6 (short-term) or prolonged (> 12 months) DAPT vs traditional 12 months in ACS patients treated with DES. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stent thrombosis. We included three randomized clinical trials and six study sub-analysis comparing alternative (short-term or prolonged) DAPT vs 12 months in post-ACS, with a total of 15,738 patients. Mortality occurred in 1.8% of patients, with no difference according to DAPT duration (short-term vs standard DAPT: OR [95% CI] 1.00 [0.72–1.39], p = 0.99; > 12 vs 12 months: OR [95% CI] 0.87 [0.61–1.22], p = 0.41). No difference in the risk of recurrent myocardial infarction and stent thrombosis was observed between short-term and standard DAPT, while a significant reduction was achieved only when extending the duration beyond 12 months (MI: OR [95% CI] 0.49 [0.36–0.67], p < 0.00001; ST: OR [95% CI] 0.40 [0.23–0.70], p = 0.001). However, prolonged DAPT was associated with a significant increase in major bleedings (OR [95% CI] 1.69 [1.17–2.45], p = 0.006). In fact, indirect comparison confirmed a significant interaction between short-term vs prolonged DAPT and the risk of myocardial infarction (p < 0.001), stent thrombosis (p = 0.0006) and major bleeding complications (p = 0.02). Based on the current meta-analysis, among ACS patients treated with percutaneous coronary interventions with DES, a shorter-term (3 or 6 months) DAPT can be safely considered, offering a non-inferior protection from major cardiovascular ischemic events as compared to the standard 12 months strategy. Extending DAPT therapy beyond 12 months enhances the antithrombotic protection, although paying the fee of increasing major bleeding complications, therefore resulting in a null effect on mortality.
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Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions et al (2013) 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. Catheter Cardiovasc Interv 82:E266–E355
Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN, ESC Scientific Document Group ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies (2018) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the task force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 39(3):213–260
Mehta SR, Bainey KR, Cantor WJ, Lordkipanidzé M, Marquis-Gravel G, Robinson SD, Sibbald M, So DY, Wong GC, Abunassar JG, Ackman ML, Bell AD, Cartier R, Douketis JD, Lawler PR, McMurtry MS, Udell JA, van Diepen S, Verma S, Mancini GBJ, Cairns JA, Tanguay JF, Members of the Secondary Panel (2018) 2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy. Can J Cardiol 34(3):214–233
Verdoia M, Schaffer A, Barbieri L, Cassetti E, Piccolo R, Galasso G, Marino P, Sinigaglia F, De Luca G (2014) Benefits from new ADP antagonists as compared with clopidogrel in patients with stable angina or acute coronary syndrome undergoing invasive management: a meta-analysis of randomized trials. J Cardiovasc Pharmacol 63(4):339–350
Wiviott SD, Braunwald E, McCabe CH, TRITON-TIMI 38 Investigators et al (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015
Wallentin L, Becker RC, Budaj A, PLATO Investigators et al (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057
Bonaca MP, Storey RF, Theroux P, Steg PG, Bhatt DL, Cohen MC, Im K, Murphy SA, Magnani G, Ophuis TO, Rudah M, Parkhomenko A, Isaza D, Kamensky G, Goudev A, Montalescot G, Jensen EC, Johanson P, Braunwald E, Sabatine MS (2017) Efficacy and safety of ticagrelor over time in patients with prior MI in PEGASUS-TIMI 54. J Am Coll Cardiol 70(11):1368–1375
Savonitto S, Ferri LA, Piatti L, Grosseto D, Piovaccari G, Morici N, Bossi I, Sganzerla P, Tortorella G, Cacucci M, Ferrario M, Murena E, Sibilio G, Tondi S, Toso A, Bongioanni S, Ravera A, Corrada E, Mariani M, Di Ascenzo L, Petronio AS, Cavallini C, Vitrella G, Rogacka R, Antonicelli R, Cesana BM, De Luca L, Ottani F, De Luca G, Piscione F, Moffa N, De Servi S, on behalf of the Elderly ACS 2 Investigators (2018) A comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization. Circulation 137(23):2435–2445
De Luca G, Navarese E, Marino P (2009) Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials. Eur Heart J 30(22):2705–2713
De Luca G, Smits P, Hofma SH, Di Lorenzo E, Vlachojannis GJ, Van’t Hof AWJ, van Boven AJ, Kedhi E, Stone GW, Suryapranata H, Drug-Eluting Stent in Primary Angioplasty (DESERT 3) cooperation (2017) Everolimus eluting stent vs first generation drug-eluting stent in primary angioplasty: a pooled patient-level meta-analysis of randomized trials. Int J Cardiol 244:121–127
De Luca G, Dirksen MT, Spaulding C, Kelbaek H, Schalij M, Thuesen L, van der Hoeven B, Vink MA, Kaiser C, Musto C, Chechi T, Spaziani G, Drug-Eluting Stent in Primary Angioplasty (DESERT) Cooperation (2012) Drug-eluting vs bare-metal stents in primary angioplasty: a pooled patient-level meta-analysis of randomized trials. Arch Intern Med 172:611–621
Biondi-Zoccai GG, Agostoni P, Abbate A, Testa L, Burzotta F, Lotrionte M, Crea F, Biasucci LM, Vetrovec GW, Colombo A (2005) Adjusted indirect comparison of intracoronary drug-eluting stents: evidence from a metaanalysis of randomized bare-metal-stent-controlled trials. Int J Cardiol 100:119–123
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W65–W94
Suryapranata H. A Randomized Trial of 3-Month vs 12-Month DAPT After Implantation of a Bioabsorbable Polymer-Based Metallic DES with a Luminal CD34 + Antibody Coating in Patients with ACS,. TCT 2017. (www.clinicaltrialresults.org)
Kedhi E, Fabris E, van der Ent M, Buszman P, von Birgelen C, Roolvink V, Zurakowski A, Schotborgh CE, Hoorntje JCA, Eek CH, Cook S, Togni M, Meuwissen M, van Royen N, van Vliet R, Wedel H, Delewi R, Zijlstra F (2018) Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial. BMJ 2(363):k3793. https://doi.org/10.1136/bmj.k3793
Hahn JY, Song YB, Oh JH, Cho DK, Lee JB, Doh JH, Kim SH, Jeong JO, Bae JH, Kim BO, Cho JH, Suh IW, Kim DI, Park HK, Park JS, Choi WG, Lee WS, Kim J, Choi KH, Park TK, Lee JM, Yang JH, Choi JH, Choi SH, Gwon HC (2018) 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial. Lancet 391:1274–1284
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, RESET Investigators (2012) 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 60:1340–1348
Schulz-Schüpke S, Byrne RA, Ten Berg JM, Neumann FJ, Han Y, Adriaenssens T, Tölg R, Seyfarth M, Maeng M, Zrenner B, Jacobshagen C, Mudra H, von Hodenberg E, Wöhrle J, Angiolillo DJ, von Merzljak B, Rifatov N, Kufner S, Morath T, Feuchtenberger A, Ibrahim T, Janssen PW, Valina C, Li Y, Desmet W, Abdel-Wahab M, Tiroch K, Hengstenberg C, Bernlochner I, Fischer M, Schunkert H, Laugwitz KL, Schömig A, Mehilli J, Kastrati A, Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) Trial Investigators (2015) ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting. Eur Heart J 36(20):1252–1263
Qi J, Li Y, Li J, Jing Q, Xu K, Gao C, Ma L, Zhang Z, Xu B, Han Y (2017) Safety and efficacy of 6-month versus 12-month dual antiplatelet therapy in patients after implantation of multiple biodegradable polymer-coated sirolimus-eluting coronary stents: insight from the I-LOVE-IT 2 trial. Catheter Cardiovasc Interv 89(S1):555–564
Collet JP, Silvain J, Barthélémy O, Rangé G, Cayla G, Van Belle E, for the ARCTIC investigators et al (2014) Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet 384(9954):1577–1585
Lee CW, Ahn JM, Park DW, Kang SJ, Lee SW, Kim YH et al (2014) Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial. Circulation 21(129):304–312
Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, the DAPT Study Investigators et al (2014) Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 371(23):2155–2166
Jang JY, Shin DH, Kim JS, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Park KW, Gwon HC, Kim HS, Jang Y (2018) Optimal duration of DAPT after second-generation drug-eluting stent in acute coronary syndrome. PLoS ONE 13(11):e0207386
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 (2010) Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 362(15):1374–1382
Gwon HC, Hahn JY, Park KW, Song YB, Chae IH, Lim DS et al (2012) 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 125:505–513
Feres F, Costa RA, Abizaid A, Leon MB, Marin-Neto JA, Botelho RV, OPTIMIZE Trial Investigators et al (2013) Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA 18(310):2510–2522
Colombo A, Chieffo A, Frasheri A, Garbo R, Masotti M, Salvatella N et al (2014) Second generation drug-eluting stents implantation followed by six versus twelve-month—dual antiplatelet therapy-the SECURITY randomized clinical trial. J Am Coll Cardiol 64:2086–2097
Helft G, Steg PG, Le Feuvre C, Georges JL, Carrie D, Dreyfus X, Furber A, Leclercq F, Eltchaninoff H, Falquier JF, Henry P, Cattan S, Sebagh L, Michel PL, Tuambilangana A, Hammoudi N, Boccara F, Cayla G, Douard H, Diallo A, Berman E, Komajda M, Metzger JP, Vicaut E, OPTImal DUAL Antiplatelet Therapy Trial Investigators (2016) Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial. Eur Heart J 37(4):365–374
Nakamura M, Iijima R, Ako J, Shinke T, Okada H, Ito Y, Ando K, Anzai H, Tanaka H, Ueda Y, Takiuchi S, Nishida Y, Ohira H, Kawaguchi K, Kadotani M, Niinuma H, Omiya K, Morita T, Zen K, Yasaka Y, Inoue K, Ishiwata S, Ochiai M, Hamasaki T, Yokoi H, NIPPON Investigators (2017) Dual antiplatelet therapy for 6 versus 18 months after biodegradable polymer drug-eluting stent implantation. JACC Cardiovasc Interv 10(12):1189–1198
Hong SJ, Shin DH, Kim JS, Kim BK, Ko YG, Choi D, Her AY, Kim YH, Jang Y, Hong MK,; IVUS-XPL Investigators (2016) 6-Month versus 12-month dual-antiplatelet therapy following long everolimus-eluting stent implantation: the IVUS-XPL randomized clinical trial. JACC Cardiovasc Interv 9(14):1438–1446
Park SJ, Park DW, Kim YH, Kang SJ, Lee SW, Lee CW et al (2010) Duration of dual antiplatelet therapy after implantation of drug-eluting stents (REAL/ZEST-LATE). N Engl J Med 362:1374–1382
Garratt KN, Weaver WD, Jenkins RD, Pow TK, Mauri L, Kereiakes DJ et al (2015) Prasugrel plus aspirin beyond 12 months is associated with improved outcomes after Taxus Liberté Paclitaxel-eluting coronary stent placement. Circulation 131(1):62–73
Hahn J-Y. P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the SMART-CHOICE randomized, open-label, noninferiority trial. Presented at ACC 2019. March 18, 2019. New Orleans, LA
Watanabe H. One-month dual antiplatelet therapy followed by clopidogrel monotherapy versus standard 12-month dual antiplatelet therapy with clopidogrel after drug-eluting stent implantation: STOPDAPT-2 trial. Presented at ACC 2019. March 18, 2019. New Orleans, LA
Mehta SR, Yusuf S, Peters RJ, Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators et al (2001) Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 358:527–533
Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C et al (2012) Short- versus long-term duration of dual antiplatelet therapy after coronary stenting (PRODIGY): a randomized multicenter trial. Circulation 125:2015–2026
Gilard M, Barragan P, Al Noryani A, Noor H, Majwal T et al (2015) Is 6 months DAPT after coronary stenting not inferior to 24 months? The Italic/Italic + Randomized trial. Results of the one year primary endpoint. J Am Coll Cardiol 65(8):777–786
De Luca G, Navarese EP, Cassetti E, Verdoia M, Suryapranata H (2011) Meta-analysis of randomized trials of glycoprotein IIb/IIIa inhibitors in high-risk acute coronary syndromes patients undergoing invasive strategy. Am J Cardiol 107:198–203
De Luca G, Gibson CM, Gyöngyösi M, Zeymer U, Dudek D, Arntz HR, Bellandi F, Maioli M, Noc M, Zorman S, Gabriel HM, Emre A, Cutlip D, Rakowski T, Huber K, van’t Hof AW (2010) Gender-related differences in outcome after ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb-IIIa inhibitors: insights from the EGYPT cooperation. J Thromb Thrombolysis 30:342–346
De Luca G, van ‘t Hof AW, Ottervanger JP, Hoorntje JC, Gosselink AT, Dambrink JH, de Boer MJ, Suryapranata H (2005) Ageing, impaired myocardial perfusion, and mortality in patients with ST-segment elevation myocardial infarction treated by primary angioplasty. Eur Heart J 26:662–666
Palmerini T, Biondi-Zoccai G, Riva DD et al (2012) Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet 379(9824):1393–1402
Lewis JM, Nawarskas JJ (2018) Are shorter durations of dual antiplatelet therapy acceptable following percutaneous coronary intervention? Cardiol Rev 26(4):213–217
Verdoia M, Pergolini P, Rolla R, Nardin M, Schaffer A, Barbieri L, Marino P, Bellomo G, Suryapranata H, De Luca G (2016) Advanced age and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor. J Thromb Haemost 14:57–64
Brener SJ, Mehran R, Dangas GD, Ohman EM, Witzenbichler B, Zhang Y, Parvataneni R, Stone GW (2017) Relation of baseline hemoglobin levels and adverse events in patients with acute coronary syndromes (from the acute catheterization and Urgent Intervention Triage strategY and harmonizing outcomes with RevasculariZatiON and stents in acute myocardial infarction trials). Am J Cardiol 119(11):1710–1716
Tsujita K, Nikolsky E, Lansky AJ, Dangas G, Fahy M, Brodie BR, Dudek D, Möckel M, Ochala A, Mehran R, Stone GW (2010) Impact of anemia on clinical outcomes of patients with ST-segment elevation myocardial infarction in relation to gender and adjunctive antithrombotic therapy (from the HORIZONS-AMI trial). Am J Cardiol 105(10):1385–1394
Baber U, Mehran R, Giustino G, Cohen DJ, Henry TD, Sartori S, Ariti C, Litherland C, Dangas G, Gibson CM, Krucoff MW, Moliterno DJ, Kirtane AJ, Stone GW, Colombo A, Chieffo A, Kini AS, Witzenbichler B, Weisz G, Steg PG, Pocock S (2016) Coronary thrombosis and major bleeding after PCI with drug-eluting stents: risk scores from PARIS. J Am Coll Cardiol 67(19):2224–2234
Barillà F, Pelliccia F, Borzi M, Camici P, Cas LD, Di Biase M, Indolfi C, Mercuro G, Montemurro V, Padeletti L, Filardi PP, Vizza CD, Romeo F, 2015–2016 Board of the Italian Society of Cardiology (2017) Optimal duration of dual anti-platelet therapy after percutaneous coronary intervention: 2016 consensus position of the Italian Society of Cardiology. J Cardiovasc Med (Hagerstown) 18(1):1–9
Palmerini T, Della Riva D, Benedetto U et al (2017) Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients. Eur Heart J 38:1034–1043
Bavishi C, Trivedi V, Singh M, Katz E, Messerli FH, Bangalore S (2017) Duration of dual antiplatelet therapy in patients with an acute coronary syndrome undergoing percutaneous coronary intervention. Am J Med 130(11):1325.e1–1325.e12
Udell JA, Bonaca MP, Collet JP, Lincoff AM, Kereiakes DJ, Costa F, Lee CW, Mauri L, Valgimigli M, Park SJ, Montalescot G, Sabatine MS, Braunwald E, Bhatt DL (2016) Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J 37(4):390–399
Vranckx P, White HD, Huang Z et al (2016) Validation of BARC bleeding criteria in patients with acute coronary syndromes: the TRACER trial. J Am Coll Cardiol 67:2135–2144
Toyota T, Shiomi H, Morimoto T, Natsuaki M, Kimura T (2017) Short versus prolonged dual antiplatelet therapy (DAPT) duration after coronary stent implantation: a comparison between the DAPT study and 9 other trials evaluating DAPT duration. PLoS ONE 12(9):e0174502
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Verdoia, M., Kedhi, E., Suryapranata, H. et al. Benefits of short-term or prolonged as compared to standard 1 year DAPT in patients with acute coronary syndrome treated with drug-eluting stents: a meta-analysis of 9 randomized trials. J Thromb Thrombolysis (2020) doi:10.1007/s11239-019-02033-2
- Dual antiplatelet therapy
- Acute coronary syndrome