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Thromb Haemost 2023; 123(08): 773-792
DOI: 10.1055/s-0043-57030
Cellular Haemostasis and Platelets

Comparison of De-escalation of DAPT Intensity or Duration in East Asian and Western Patients with ACS Undergoing PCI: A Systematic Review and Meta-analysis

Diana A. Gorog 
1   Faculty of Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom
2   Centre for Health Services and Clinical Research, Postgraduate Medical School, University of Hertfordshire, Hertfordshire, United Kingdom
,
Visvesh Jeyalan
3   Department of Cardiology, Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
,
Rafaella I. L. Markides
4   University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridgeshire, United Kingdom
,
Eliano P. Navarese
5   Interventional Cardiology and Cardiovascular Medicine Research, Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
6   Department of Cardiology, Faculty of Medicine, University of Alberta, Edmonton, Canada
,
Young-Hoon Jeong 
7   CAU Thrombosis and Biomarker Center, Chung-Ang University, Gwangmyeong Hospital, Seoul, Republic of Korea
8   Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea
,
Mohamed Farag 
2   Centre for Health Services and Clinical Research, Postgraduate Medical School, University of Hertfordshire, Hertfordshire, United Kingdom
3   Department of Cardiology, Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
› Author Affiliations Funding None.
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Abstract

Background Guideline-recommended dual antiplatelet therapy (DAPT; aspirin plus prasugrel/ticagrelor) for 12 months in acute coronary syndrome (ACS) patients increases bleeding, with East Asians (EAs) exhibiting higher bleeding and lower ischemic risk, compared with non-East Asians (nEAs). We sought to compare DAPT “de-escalation” strategies in EA and nEA populations.

Methods A systematic review and meta-analysis of randomized controlled trials assessing reduction of DAPT intensity or duration in ACS patients undergoing percutaneous coronary intervention, in EA and nEA, was performed using a random-effects model.

Results Twenty-three trials assessed reduction of DAPT intensity (n = 12) or duration (n = 11). Overall, reduced DAPT intensity attenuated major bleeding (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.65–0.94, p = 0.009), without impacting net adverse cardiovascular events (NACE) or major adverse cardiovascular events (MACE). In nEA, this increased MACE (OR: 1.20, 95% CI: 1.09–1.31, p < 0.0001) without impacting NACE or bleeding; while in EA, it reduced major bleeding (OR: 0.71, 95% CI: 0.53–0.95, p = 0.02) without affecting NACE or MACE. Overall, abbreviation of DAPT duration reduced NACE (OR: 0.90, 95% CI: 0.82–0.99, p = 0.03) due to major bleeding (OR: 0.69, 95% CI: 0.53–0.99, p = 0.006), without impacting MACE. In nEA, this strategy did not impact NACE, MACE, or major bleeding; while in EA, it reduced major bleeding (OR: 0.60, 95% CI: 0.4–0.91, p = 0.02) without impacting NACE or MACE.

Conclusion In EA, reduction of DAPT intensity or duration can minimize bleeding, without safety concerns. In nEA, reduction of DAPT intensity may incur an ischemic penalty, while DAPT abbreviation has no overall benefit.

Keywords

dual antiplatelet therapy - de-escalation - acute coronary syndrome - bleeding - East Asian

Supplementary Material



Publication History

Received: 21 January 2023

Accepted: 17 March 2023

Article published online:
18 April 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Collet J-P, Thiele H, Barbato E. et al; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021; 42 (14) 1289-1367
    CrossrefPubMedGoogle Scholar
  • 2 Ibanez B, James S, Agewall S. et al; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39 (02) 119-177
    CrossrefPubMedGoogle Scholar
  • 3 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 Heart J 2018; 39: 213-260
    CrossrefPubMedGoogle Scholar
  • 4 Wiviott SD, Braunwald E, McCabe CH. et al; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357 (20) 2001-2015
    CrossrefPubMedGoogle Scholar
  • 5 Wallentin L, Becker RC, Budaj A. et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11) 1045-1057
    CrossrefPubMedGoogle Scholar
  • 6 Eisen A, Giugliano RP, Braunwald E. Updates on acute coronary syndrome: a review. JAMA Cardiol 2016; 1 (06) 718-730
    CrossrefPubMedGoogle Scholar
  • 7 Mehran R, Pocock SJ, Stone GW. et al. Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial. Eur Heart J 2009; 30 (12) 1457-1466
    CrossrefPubMedGoogle Scholar
  • 8 Cao D, Mehran R, Dangas G. et al. Validation of the Academic Research Consortium high bleeding risk definition in contemporary PCI patients. J Am Coll Cardiol 2020; 75 (21) 2711-2722
    CrossrefPubMedGoogle Scholar
  • 9 Kim HK, Tantry US, Smith Jr SC. et al. The East Asian Paradox: an updated position statement on the challenges to the current antithrombotic strategy in patients with cardiovascular disease. Thromb Haemost 2021; 121 (04) 422-432
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Cho H, Kang J, Kim HS, Park KW. Ethnic differences in oral antithrombotic therapy. Korean Circ J 2020; 50 (08) 645-657
    CrossrefPubMedGoogle Scholar
  • 11 Scott SA, Sangkuhl K, Stein CM. et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther 2013; 94 (03) 317-323
    CrossrefPubMedGoogle Scholar
  • 12 Levine GN, Jeong YH, Goto S. et al. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol 2014; 11 (10) 597-606
    CrossrefPubMedGoogle Scholar
  • 13 Huo Y, Jeong YH, Gong Y. et al. 2018 update of expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Sci Bull (Beijing) 2019; 64 (03) 166-179
    CrossrefPubMedGoogle Scholar
  • 14 Kwon O, Park DW. Antithrombotic therapy after acute coronary syndromes or percutaneous coronary interventions in East Asian populations. JACC Asia 2022; 2 (01) 1-18
    CrossrefPubMedGoogle Scholar
  • 15 Higgins JPT, Altman DG, Gøtzsche PC. et al; Cochrane Bias Methods Group, Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928
    CrossrefPubMedGoogle Scholar
  • 16 Saito S, Isshiki T, Kimura T. et al. Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. Circ J 2014; 78 (07) 1684-1692
    CrossrefPubMedGoogle Scholar
  • 17 Goto S, Huang CH, Park SJ, Emanuelsson H, Kimura T. Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome – randomized, double-blind, phase III PHILO study. Circ J 2015; 79 (11) 2452-2460
    CrossrefPubMedGoogle Scholar
  • 18 Tang X, Li R, Jing Q. et al. Assessment of ticagrelor versus clopidogrel treatment in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. J Cardiovasc Pharmacol 2016; 68 (02) 115-120
    CrossrefPubMedGoogle Scholar
  • 19 Wang H, Wang X. Efficacy and safety outcomes of ticagrelor compared with clopidogrel in elderly Chinese patients with acute coronary syndrome. Ther Clin Risk Manag 2016; 12: 1101-1105
    CrossrefPubMedGoogle Scholar
  • 20 Park DW, Kwon O, Jang JS. et al; TICAKOREA Investigators. Clinically significant bleeding with ticagrelor versus clopidogrel in Korean patients with acute coronary syndromes intended for invasive management: a randomized clinical trial. Circulation 2019; 140 (23) 1865-1877
    CrossrefPubMedGoogle Scholar
  • 21 Kim CJ, Park MW, Kim MC. et al; TALOS-AMI investigators. Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial. Lancet 2021; 398 (10308): 1305-1316
    CrossrefPubMedGoogle Scholar
  • 22 Kim HS, Kang J, Hwang D. et al; HOST-REDUCE-POLYTECH-ACS investigators. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial. Lancet 2020; 396 (10257): 1079-1089
    CrossrefPubMedGoogle Scholar
  • 23 Gimbel M, Qaderdan K, Willemsen L. et al. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet 2020; 395 (10233): 1374-1381
    CrossrefPubMedGoogle Scholar
  • 24 Savonitto S, Ferri LA, Piatti L. et al; Elderly ACS 2 Investigators. Comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization. Circulation 2018; 137 (23) 2435-2445
    CrossrefPubMedGoogle Scholar
  • 25 Cuisset T, Deharo P, Quilici J. et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J 2017; 38 (41) 3070-3078
    CrossrefPubMedGoogle Scholar
  • 26 Schmucker J, Fach A, Mata Marin LA. et al. Efficacy and safety of ticagrelor in comparison to clopidogrel in elderly patients with ST-segment-elevation myocardial infarctions. J Am Heart Assoc 2019; 8 (18) e012530
    CrossrefPubMedGoogle Scholar
  • 27 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 (03) 505-513
    CrossrefPubMedGoogle Scholar
  • 28 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 (02) e003145
    PubMedGoogle Scholar
  • 29 Hahn JY, Song YB, Oh JH. et al; SMART-DATE investigators. 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): 1274-1284
    CrossrefPubMedGoogle Scholar
  • 30 Vranckx P, Valgimigli M, Jüni P. et al; GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet 2018; 392 (10151): 940-949
    CrossrefPubMedGoogle Scholar
  • 31 Vranckx P, Valgimigli M, Odutayo A. et al; GLOBAL LEADERS Investigators. Efficacy and safety of ticagrelor monotherapy by clinical presentation: pre-specified analysis of the GLOBAL LEADERS trial. J Am Heart Assoc 2021; 10 (18) e015560
    CrossrefPubMedGoogle Scholar
  • 32 De Luca G, Damen SA, Camaro C. et al; Collaborators. Final results of the randomised evaluation of short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with a new-generation stent (REDUCE trial). EuroIntervention 2019; 15 (11) e990-e998
    CrossrefPubMedGoogle Scholar
  • 33 Mehran R, Baber U, Sharma SK. et al. Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med 2019; 381 (21) 2032-2042
    CrossrefPubMedGoogle Scholar
  • 34 Hahn JY, Song YB, Oh JH. et al; SMART-CHOICE Investigators. 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 2019; 321 (24) 2428-2437
    CrossrefPubMedGoogle Scholar
  • 35 Watanabe H, Domei T, Morimoto T. et al; STOPDAPT-2 Investigators. 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) 2414-2427
    CrossrefPubMedGoogle Scholar
  • 36 Watanabe H, Morimoto T, Natsuaki M. et al; STOPDAPT-2 ACS Investigators. Comparison of clopidogrel monotherapy after 1 to 2 months of dual antiplatelet therapy with 12 months of dual antiplatelet therapy in patients with acute coronary syndrome: the STOPDAPT-2 ACS randomized clinical trial. JAMA Cardiol 2022; 7 (04) 407-417
    CrossrefPubMedGoogle Scholar
  • 37 Kim BK, Hong SJ, Cho YH. et al; TICO Investigators. Effect of ticagrelor monotherapy vs ticagrelor with aspirin on major bleeding and cardiovascular events in patients with acute coronary syndrome: the TICO randomized clinical trial. JAMA 2020; 323 (23) 2407-2416
    CrossrefPubMedGoogle Scholar
  • 38 Valgimigli M, Frigoli E, Heg D. et al; MASTER DAPT Investigators. Dual antiplatelet therapy after PCI in patients at high bleeding risk. N Engl J Med 2021; 385 (18) 1643-1655
    CrossrefPubMedGoogle Scholar
  • 39 Han Y, Claessen BE, Chen SL. et al. Ticagrelor with or without aspirin in chinese patients undergoing percutaneous coronary intervention: a TWILIGHT China substudy. Circ Cardiovasc Interv 2022; 15 (04) e009495
    PubMedGoogle Scholar
  • 40 Laudani C, Greco A, Occhipinti G. et al. Short duration of DAPT versus de-escalation after percutaneous coronary intervention for acute coronary syndromes. JACC Cardiovasc Interv 2022; 15 (03) 268-277
    CrossrefPubMedGoogle Scholar
  • 41 Shoji S, Kuno T, Fujisaki T. et al. De-escalation of dual antiplatelet therapy in patients with acute coronary syndromes. J Am Coll Cardiol 2021; 78 (08) 763-777
    CrossrefPubMedGoogle Scholar
  • 42 Ueshima H, Sekikawa A, Miura K. et al. Cardiovascular disease and risk factors in Asia: a selected review. Circulation 2008; 118 (25) 2702-2709
    CrossrefPubMedGoogle Scholar
  • 43 Albert MA, Glynn RJ, Buring J, Ridker PM. C-reactive protein levels among women of various ethnic groups living in the United States (from the Women's Health Study). Am J Cardiol 2004; 93 (10) 1238-1242
    CrossrefPubMedGoogle Scholar
  • 44 Kelley-Hedgepeth A, Lloyd-Jones DM, Colvin A. et al; SWAN Investigators. Ethnic differences in C-reactive protein concentrations. Clin Chem 2008; 54 (06) 1027-1037
    CrossrefPubMedGoogle Scholar
  • 45 Kim HK, Tantry US, Park HW. et al. Ethnic difference of thrombogenicity in patients with cardiovascular disease: a pandora box to explain prognostic differences. Korean Circ J 2021; 51 (03) 202-221
    CrossrefPubMedGoogle Scholar
  • 46 Lutsey PL, Cushman M, Steffen LM. et al. Plasma hemostatic factors and endothelial markers in four racial/ethnic groups: the MESA study. J Thromb Haemost 2006; 4 (12) 2629-2635
    CrossrefPubMedGoogle Scholar