Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286


Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

Author(s): Jieqiong Guan, Wenjing Song, Pan He, Siyu Fan, Hong Zhi and Lina Wang*

Volume 26 , Issue 44 , 2020

Page: [5739 - 5745] Pages: 7

DOI: 10.2174/1381612826666200625110349

Price: $65


Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent.

Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial.

Methods: PubMed, Cochrane Library, Web of Science,, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis.

Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup.

Conclusion: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

Keywords: Dual antiplatelet therapy, duration, drug-eluting stents, network meta-analysis, coronary artery disease, monotherapy.

Lugo LM, Ferreiro JL. Dual antiplatelet therapy after coronary stent implantation: Individualizing the optimal duration. J Cardiol 2018; 72(2): 94-104.
[] [PMID: 29602648]
Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American college of cardiology/american heart association task force on clinical practice guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. J Am Coll Cardiol 2016; 68(10): 1150-1.
[] [PMID: 27585519]
Valgimigli M, Bueno H, Byrne RA, et al. 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 J Cardio-Thorac 2018; 53(1): 34-78.
Watanabe H, Domei T, Morimoto T, et al. Effect of 1-month dual antiplatelet therapy followed by clopidogrel vs. 12-month dual antiplatelet therapy on cardiovascular and bleeding events in patients receiving PCI: The STOPDAPT-2 randomized clinical trial. JAMA 2019; 321(24): 2414-27.
[] [PMID: 31237644]
Hahn JY, Bin Song Y, Oh JH, et al. Effect of P2Y12 inhibitor monotherapy vs. dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention the SMART-CHOICE randomized clinical trial. Jama-J Am Med Assoc 2019; 321(24): 2428-37.
Helft G, Steg PG, Le Feuvre C, et al. Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial Eur Heart J 2016; 37(4): 365-74.
[PMID: 26364288]
Feres F, Costa RA, Abizaid A, et al. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents the OPTIMIZE randomized trial. Jama-J Am Med Assoc 2013; 310(23): 2510-22.
Hahn JY, Song YB, Oh JH, et al. 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 2018; 391(10127): 1274-84.
[] [PMID: 29544699]
Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med 2004; 23(20): 3105-24.
[] [PMID: 15449338]
Salanti G, Higgins JPT, Ades AE, Ioannidis JPA. Evaluation of networks of randomized trials. Stat Methods Med Res 2008; 17(3): 279-301.
[] [PMID: 17925316]
Yin SHL, Xu P, Wang B, et al. Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis Bmj-Brit Med J 2019; 365.
Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 2015; 162(11): 777-84.
[] [PMID: 26030634]
Brooks SP, Gelman A. General methods for monitoring convergence of iterative simulations. J Comput Graph Stat 1998; 7(4): 434-55.
Chaimani A, Higgins JPT, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One 2013; 8(10): e76654.
[] [PMID: 24098547]
Chaimani A, Salanti G. Visualizing assumptions and results in network meta-analysis: The network graphs package. Stata J 2015; 15(4): 905-50.
Kedhi E, Fabris E, van der Ent M, et al. 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 2018; 363: k3793.
[] [PMID: 30279197]
Nakamura M, Iijima R, Ako J, et al. Dual antiplatelet therapy for 6 versus 18 months after biodegradable polymer drug-eluting stent implantation. JACC Cardiovasc Interv 2017; 10(12): 1189-98.
[] [PMID: 28641838]
Didier R, Morice MC, Barragan P, et al. 6-versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin final results of the ITALIC trial (Is there a life for des after discontinuation of clopidogrel). Jacc-Cardiovasc Inte 2017; 10(12): 1202-10.
Hong S-J, Shin D-H, Kim J-S, et al. 6-month versus 12-month dual-antiplatelet therapy following long everolimus-eluting stent implantation: The IVUS-XPL randomized clinical trial. JACC Cardiovasc Interv 2016; 9(14): 1438-46.
[] [PMID: 27212028]
Schulz-Schüpke S, Byrne RA, Ten Berg JM, et al. 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(20): 1252-63.
[] [PMID: 25616646]
Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; 371(23): 2155-66.
[] [PMID: 25399658]
Lee CW, Ahn JM, Park DW, et al. Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial. Circulation 2014; 129(3): 304-12.
[] [PMID: 24097439]
Colombo A, Chieffo A, Frasheri A, et al. 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(20): 2086-97.
[] [PMID: 25236346]
Collet J-P, Silvain J, Barthélémy O, et al. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet 2014; 384(9954): 1577-85.
[] [PMID: 25037988]
Feres F, Costa RA, Abizaid A, et al. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA 2013; 310(23): 2510-22.
[] [PMID: 24177257]
Valgimigli M, Campo G, Monti M, et al. Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation 2012; 125(16): 2015-26.
[] [PMID: 22438530]
Kim BK, Hong MK, Shin DH, et al. 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(15): 1340-8.
[] [PMID: 22999717]
Gwon HC, Hahn JY, Park KW, et al. 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(3): 505-13.
[] [PMID: 22179532]
Han Y, Xu B, Xu K, et al. Six versus 12 months of dual antiplatelet therapy after implantation of biodegradable polymer sirolimus-eluting stent: randomized substudy of the I-LOVE-IT 2 Trial. Circ Cardiovasc Interv 2016; 9(2): e003145.
[] [PMID: 26858080]
Lee BK, Kim JS, Lee OH, et al. Safety of six-month dual antiplatelet therapy after second-generation drug-eluting stent implantation: OPTIMA-C Randomised Clinical Trial and OCT Substudy. EuroIntervention 2018; 13(16): 1923-30.
[] [PMID: 29104179]
Moshfegh K, Redondo M, Julmy F, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 2000; 36(3): 699-705.
[] [PMID: 10987587]
Hao QK, Tampi M, O'Donnell M, et al. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis Bmj-Brit Med J 2018; 363.
Palmerini T, Della Riva D, Benedetto U, et al. 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 2017; 38(14): 1034-43.
[] [PMID: 28110296]
Gajulapalli RD, Dias S, Pattanshetty DJ, Athappan G. Optimal duration of dual antiplatelet therapy after drug eluting stent implantation: a network meta-analysis. Anatol J Cardiol 2017; 18(4): 251-60.
[] [PMID: 29076813]
Capodanno D, Mehran R, Valgimigli M, et al. Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention. Nat Rev Cardiol 2018; 15(8): 480-96.
[] [PMID: 29973709]
Verdoia M, Khedi E, Ceccon C, Suryapranata H, De Luca G. Duration of dual antiplatelet therapy and outcome in patients with acute coronary syndrome undergoing percutaneous revascularization: A meta-analysis of 11 randomized trials. Int J Cardiol 2018; 264: 30-8.
[] [PMID: 29776573]
Mavrakanas TA, Chatzizisis YS, Gariani K, et al. Duration of dual antiplatelet therapy in patients with CKD and drug-eluting stents a meta-analysis. Clin J Am Soc Nephrol 2019; 14(6): 810-22.
Sharma A, Garg A, Elmariah S, et al. Duration of dual antiplatelet therapy following drug-eluting stent implantation in diabetic and non-diabetic patients: A systematic review and meta-analysis of randomized controlled trials. Prog Cardiovasc Dis 2018; 60(4-5): 500-7.
[] [PMID: 29277295]
Yeh RW, Secemsky EA, Kereiakes DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. Jama-J Am Med Assoc 2016; 315(16): 1735-49.
Baber U, Mehran R, Giustino G, et al. Coronary thrombosis and major bleeding after PCI with drug-eluting stents: Risk scores from PARIS. J Am Coll Cardiol 2016; 67(19): 2224-34.
[] [PMID: 27079334]
Costa F, van Klaveren D, James S, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017; 389(10073): 1025-34.
[] [PMID: 28290994]
Costa F, Van Klaveren D, Feres F, et al. Dual antiplatelet therapy duration based on ischemic and bleeding risks after coronary stenting. J Am Coll Cardiol 2019; 73(7): 741-54.
[] [PMID: 30784667 ]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy