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CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(01): 108-117
DOI: 10.1055/s-0042-1757405
Atherosclerosis and Ischaemic Disease

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials

Qiao-Yu Shao
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Zhi-Jian Wang
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Xiao-Teng Ma
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Yu-Fei Wang
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Qiu-Xuan Li
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Zhi Qiang Yang
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Xu-Ze Lin
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Liu Pan
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Fei Gao
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Li Xia Yang
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Jing Liang
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Yu-Jie Zhou
1   Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
› Institutsangaben Funding This project was funded by the National Key Research and Development Program of China (2017YFC0908800, to Yu-Jie Zhou), the Beijing Municipal Administration of Hospitals' Mission plan (SML20180601, to Yu-Jie Zhou), the China Postdoctoral Science Foundation (2021M692253, to Xiao-Teng Ma), the Beijing Postdoctoral Research Foundation (2021-ZZ-023, to Xiao-Teng Ma), the National Natural Science Foundation of China (81670391, to Zhi-Jian Wang).
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Abstract

Background The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events.

Objectives We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events.

Methods We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis.

Results Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85–1.04; modulation: RR: 0.90; 95% CI: 0.81–1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76–0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15–1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96–1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51–0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI.

Conclusion Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Keywords

coronary artery disease - mortality - antiplatelet - anticoagulant - meta-analysis

Authors' Contributions

All authors contributed to study concept and design; Q.Y.S. and X.T.M. contributed to acquisition of data; Z.J.W. and Q.Y.S. did the statistical analysis; Q.Y.S. drafted the report; Z.J.W. contributed to critical revision of the manuscript for important intellectual content. All authors read and approved the final draft of the manuscript.


Ethics Committee Approval

This study was approved by the institutional review board of Beijing Anzhen Hospital, Capital Medical University.


Supplementary Material



Publikationsverlauf

Eingereicht: 03. März 2022

Angenommen: 02. August 2022

Artikel online veröffentlicht:
07. November 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Neumann FJ, Sousa-Uva M, Ahlsson A. et al; ESC Scientific Document Group. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J 2019; 40 (02) 87-165
    CrossrefPubMedGoogle Scholar
  • 2 Valgimigli M, Bueno H, Byrne RA. et al; ESC Scientific Document Group, ESC Committee for Practice Guidelines (CPG), ESC National Cardiac Societies. 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 (03) 213-260
    CrossrefPubMedGoogle Scholar
  • 3 Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345 (07) 494-502
    CrossrefPubMedGoogle Scholar
  • 4 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
  • 5 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
  • 6 Valgimigli M, Costa F, Lokhnygina Y. et al. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial. Eur Heart J 2017; 38 (11) 804-810
    PubMedGoogle Scholar
  • 7 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
  • 8 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
  • 9 Rao AK, Pratt C, Berke A. et al. Thrombolysis in Myocardial Infarction (TIMI) Trial–phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11 (01) 1-11
    CrossrefPubMedGoogle Scholar
  • 10 Mehran R, Rao SV, Bhatt DL. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123 (23) 2736-2747
    CrossrefPubMedGoogle Scholar
  • 11 GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329 (10) 673-682
    CrossrefPubMedGoogle Scholar
  • 12 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
    CrossrefPubMedGoogle Scholar
  • 13 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7 (03) 177-188
    CrossrefPubMedGoogle Scholar
  • 14 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
    CrossrefPubMedGoogle Scholar
  • 15 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
  • 16 Généreux P, Giustino G, Witzenbichler B. et al. Incidence, predictors, and impact of post-discharge bleeding after percutaneous coronary intervention. J Am Coll Cardiol 2015; 66 (09) 1036-1045
    CrossrefPubMedGoogle Scholar
  • 17 Campo G, Parrinello G, Ferraresi P. et al. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol 2011; 57 (25) 2474-2483
    CrossrefPubMedGoogle Scholar
  • 18 Kereiakes DJ, Yeh RW, Massaro JM. et al; Dual Antiplatelet Therapy (DAPT) Study Investigators. Antiplatelet therapy duration following bare metal or drug-eluting coronary stents: the dual antiplatelet therapy randomized clinical trial. JAMA 2015; 313 (11) 1113-1121
    CrossrefPubMedGoogle Scholar
  • 19 Aradi D, Kirtane A, Bonello L. et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; 36 (27) 1762-1771
    CrossrefPubMedGoogle Scholar
  • 20 Sibbing D, Aradi D, Alexopoulos D. et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv 2019; 12 (16) 1521-1537
    CrossrefPubMedGoogle Scholar
  • 21 Galli M, Franchi F, Rollini F. et al. Genetic testing in patients undergoing percutaneous coronary intervention: rationale, evidence and practical recommendations. Expert Rev Clin Pharmacol 2021; 14 (08) 963-978
    CrossrefPubMedGoogle Scholar
  • 22 Sibbing D, Aradi D, Jacobshagen C. et al; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet 2017; 390 (10104): 1747-1757
    CrossrefPubMedGoogle Scholar
  • 23 Claassens DMF, Vos GJA, Bergmeijer TO. et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med 2019; 381 (17) 1621-1631
    CrossrefPubMedGoogle Scholar
  • 24 Galli M, Benenati S, Franchi F. et al. Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials. Eur Heart J 2022; 43 (10) 959-967
    CrossrefPubMedGoogle Scholar
  • 25 Tavenier AH, Mehran R, Chiarito M. et al. Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with ACS: a meta-analysis. Eur Heart J Cardiovasc Pharmacother 2022; 8 (05) 492-502
    CrossrefPubMedGoogle Scholar
  • 26 Galli M, Benenati S, Capodanno D. et al. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Lancet 2021; 397 (10283): 1470-1483
    CrossrefPubMedGoogle Scholar
  • 27 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
  • 28 Pereira NL, Farkouh ME, So D. et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA 2020; 324 (08) 761-771
    CrossrefPubMedGoogle Scholar
  • 29 Bergmeijer TO, Janssen PWA, Asselbergs FW. et al. A tailored antiplatelet strategy in STEMI patients based on CYP2C19 genotyping is feasible in daily practice-POPular Genetics study. Eur Heart J 2014; 35: 191-192
    PubMedGoogle Scholar