SYSTEMATIC REVIEW
Optimal dual antiplatelet therapy for coronary artery bypass grafting: a systematic review and meta-analysis
1
Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
2
Department of Medicine, Akhtar Saeed Medical and Dental College, Lahore, Pakistan
3
Department of Medicine, Shaikh Zayed Hospital, Lahore, Pakistan
4
Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan
5
Department of Medicine, Khyber Medical College, Peshawar, Pakistan
6
Sunderland Royal Hospital, Sunderland, United Kingdom
7
National Heart and Lung Institute, Imperial College London, London, United Kingdom
8
Aston University, Birmingham, UK
9
Queen Elizabeth Hospital, Birmingham, UK
Submission date: 2025-01-12
Acceptance date: 2025-02-25
Publication date: 2025-03-20
Corresponding author
Raheel Ahmed
National Heart and Lung Institute Imperial College London London, United Kingdom Phone: +44 7888 921532
National Heart and Lung Institute Imperial College London London, United Kingdom Phone: +44 7888 921532
Arch Med Sci Atheroscler Dis 2025;10(1):16-27
KEYWORDS
TOPICS
ABSTRACT
Introduction:
This meta-analysis evaluated the efficacy and safety of dual antiplatelet therapy (DAPT) with aspirin combined with ticagrelor, clopidogrel, or prasugrel in coronary artery bypass grafting (CABG) patients.
Material and Methods:
Nineteen studies involving 9,585 patients were included.
Results:
Post-CABG administration of ticagrelor significantly reduced all-cause mortality (OR = 0.49 [0.33, 0.73]; p < 0.01) and minimized major bleeding when discontinued more than 3 days before surgery (OR = 0.62 [0.47, 0.83]; p < 0.01). Ticagrelor exhibited a non-significant trend toward reducing both re-bleeding and the need for platelet transfusions. Prasugrel was associated with a higher requirement for platelet transfusions (OR = 1.88; 95% CI: 1.24-2.87; p < 0.01). No significant associations were found for myocardial infarction, stroke, or RBC transfusion.
Conclusions:
In CABG patients, DAPT with aspirin and ticagrelor offers the best balance between efficacy and safety, improving key outcomes while managing bleeding risk. Prasugrel’s increased bleeding risk requires caution in its use.
This meta-analysis evaluated the efficacy and safety of dual antiplatelet therapy (DAPT) with aspirin combined with ticagrelor, clopidogrel, or prasugrel in coronary artery bypass grafting (CABG) patients.
Material and Methods:
Nineteen studies involving 9,585 patients were included.
Results:
Post-CABG administration of ticagrelor significantly reduced all-cause mortality (OR = 0.49 [0.33, 0.73]; p < 0.01) and minimized major bleeding when discontinued more than 3 days before surgery (OR = 0.62 [0.47, 0.83]; p < 0.01). Ticagrelor exhibited a non-significant trend toward reducing both re-bleeding and the need for platelet transfusions. Prasugrel was associated with a higher requirement for platelet transfusions (OR = 1.88; 95% CI: 1.24-2.87; p < 0.01). No significant associations were found for myocardial infarction, stroke, or RBC transfusion.
Conclusions:
In CABG patients, DAPT with aspirin and ticagrelor offers the best balance between efficacy and safety, improving key outcomes while managing bleeding risk. Prasugrel’s increased bleeding risk requires caution in its use.
REFERENCES (55)
1.
Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009; 360: 961-72.
2.
Doenst T, Haverich A, Serruys P, et al. PCI and CABG for treating stable coronary artery disease: JACC review topic of the week. J Am Coll Cardiol 2019; 73: 964-76.
3.
Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012; 60: 2564-603.
4.
Goldman S, Zadina K, Moritz T, et al. Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study J Am Coll Cardiol 2004; 44: 2149-56.
5.
Buxton BF, Hayward PA, Raman J, et al. Long-term results of the RAPCO trials. Circulation 2020; 142: 1330-8.
6.
Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am Coll Cardiol 1996; 28: 616-26.
7.
Gaudino M, Antoniades C, Benedetto U, et al. Mechanisms, consequences, and prevention of coronary graft failure. Circulation 2017; 136: 1749-64.
8.
Sopek-Merkaš I, Lakušić N, Fučkar K, Cerovec D, Bešić KM. Antiplatelet therapy after coronary artery bypass graft surgery – unevenness of daily clinical practice. Acta Clin Croat 2021; 60: 540-3.
9.
Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005; 353: 2373-83.
10.
Authors/Task Force members, Windecker S, Kolh P, et al. 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: 2541-619.
11.
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. Circulation 2016; 134: e123-55.
12.
Choong CK, Gerrard C, Goldsmith KA, Dunningham H, Vuylsteke A. Delayed re-exploration for bleeding after coronary artery bypass surgery results in adverse outcomes. Eur J Cardiothorac Surg 2007; 31: 834-8.
13.
Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 2010; 304: 1821-30.
14.
Dai L, Xu J, Jiang Y, Chen K. Impact of prasugrel and ticagrelor on platelet reactivity in patients with acute coronary syndrome: a meta-analysis. Front Cardiovasc Med 2022; 9: 905607.
15.
Cannon CP, Harrington RA, James S, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 2010; 375: 283-93.
16.
James SK, Roe MT, Cannon CP, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. BMJ 2011; 342: d3527.
17.
Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
18.
Weidinger F. Discontinuation of P2Y12 antagonists before coronary bypass surgery: is 5 days really required? Eur Heart J 2016; 37: 198-9.
19.
Levine GN, Bates ER, Blankenship JC, et al. 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. Circulation 2011; 124: e574-651.
20.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097.
21.
Higgins J, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. Wiley 2019.
22.
Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
23.
Ottawa Hospital Research Institute. Accessed August 20, 2024. https://www.ohri.ca/programs/c....
24.
Chang HW, Kim HJ, Yoo JS, Kim DJ, Cho KR. Clopidogrel versus ticagrelor for secondary prevention after coronary artery bypass grafting. J Clin Med 2019; 8: 104.
25.
Della Corte A, Bancone C, Spadafora A, et al. Postoperative bleeding in coronary artery bypass patients on double antiplatelet therapy: predictive value of preoperative aggregometry. Eur J Cardiothorac Surg 2017; 52: 901-8.
26.
Dery J, Dagenais F, Mohammadi S, et al. RISK of bleeding complications in patients treated with ticagrelor undergoing urgent coronary artery bypass grafting surgery: a single center experience. Can J Cardiol 2014; 30: S328.
27.
Hansson EC, Jidéus L, Åberg B, et al. Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study. Eur Heart J 2016; 37: 189-97.
28.
Holm M, Biancari F, Khodabandeh S, et al. Bleeding in patients treated with ticagrelor or clopidogrel before coronary artery bypass grafting. Ann Thorac Surg 2019; 107: 1690-8.
29.
Ingrassia JJ, Mosleh W, Conner CM, et al. Impact of Ticagrelor versus clopidogrel on bleeding outcomes of isolated coronary artery bypass grafting. Cardiovasc Revascularization Med Mol Interv 2023; 46: 44-51.
30.
Held C, Asenblad N, Bassand JP, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. J Am Coll Cardiol 2011; 57: 672-84.
31.
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-57.
32.
Russo JJ, James TE, Ruel M, et al. Ischemic and bleeding outcomes after coronary artery bypass grafting among patients initially treated with a P2Y12 receptor antagonist for acute coronary syndromes: insights on timing of discontinuation of ticagrelor and clopidogrel prior to surgery. Eur Heart J Acute Cardiovasc Care 2019; 8: 543-53.
33.
Schaefer A, Sill B, Schoenebeck J, et al. Preoperative Ticagrelor administration leads to a higher risk of bleeding during and after coronary bypass surgery in a case-matched analysis. Interact Cardiovasc Thorac Surg 2016; 22: 136-40.
34.
Tang Y, Fan X, Zhang B, et al. Aspirin plus ticagrelor or clopidogrel on graft patency one year after coronary bypass grafting: a single-center, randomized, controlled trial. J Thorac Dis 2021; 13: 1697-705.
35.
Tomšič A, Schotborgh MA, Manshanden JSJ, Li WWL, de Mol BAJM. Coronary artery bypass grafting-related bleeding complications in patients treated with dual antiplatelet treatment. Eur J Cardiothorac Surg 2016; 50: 849-56.
36.
Varma PK, Ahmed H, Krishna N, et al. Bleeding complications after dual antiplatelet therapy with ticagrelor versus dual antiplatelet therapy with clopidogrel-a propensity-matched comparative study of two antiplatelet regimes in off-pump coronary artery bypass grafting. Indian J Thorac Cardiovasc Surg 2021; 37: 27-37.
37.
Voetsch A, Pregartner G, Berghold A, et al. How do type of preoperative P2Y12 receptor inhibitor and withdrawal time affect bleeding? Ann Thorac Surg 2021; 111: 77-84.
38.
Vuilliomenet T, Gebhard C, Bizzozero C, et al. Discontinuation of dual antiplatelet therapy and bleeding in intensive care in patients undergoing urgent coronary artery bypass grafting: a retrospective analysis. Interact Cardiovasc Thorac Surg 2019; 28: 665-73.
39.
Yan H, Tiemuerniyazi X, Song Y, Xu F, Feng W. Comparison of dual antiplatelet therapies after coronary endarterectomy combined with coronary artery bypass grafting: a cohort study. J Cardiothorac Surg 2020; 15: 155.
40.
Wang Z, Li X, Ye Y, et al. Preoperative treatment with clopidogrel and ticagrelor on bleeding complications in off-pump coronary artery bypass grafting. Thromb Res 2022; 219: 70-6.
41.
Wang Z, Zou Y, Xia L, et al. Does thromboelastography predict bleeding in patients treated with clopidogrel or ticagrelor in off-pump coronary artery bypass grafting? Thromb Res 2022; 213: 145-53.
42.
Smith PK, Goodnough LT, Levy JH, et al. Mortality benefit with prasugrel in the TRITON-TIMI 38 coronary artery bypass grafting cohort: risk-adjusted retrospective data analysis. J Am Coll Cardiol 2012; 60: 388-96.
43.
Drews S, Bolliger D, Kaiser C, et al. Prasugrel increases the need for platelet transfusions and surgical reexploration rates compared with clopidogrel in coronary artery bypass surgery. Thorac Cardiovasc Surg 2015; 63: 28-35.
44.
Comanici M, Bhudia SK, Marczin N, Raja SG. Antiplatelet resistance in patients who underwent coronary artery bypass grafting: a systematic review and meta-analysis. Am J Cardiol 2023; 206: 191-9.
45.
Sandner S, Redfors B, Angiolillo DJ, et al. Association of dual antiplatelet therapy with ticagrelor with vein graft failure after coronary artery bypass graft surgery: a systematic review and meta-analysis. JAMA 2022; 328: 554-62.
46.
Hasan SU, Pervez A, Afreen M, et al. Comparative effectiveness of antiplatelet therapies for saphenous venous graft occlusion and cardiovascular outcomes: a network meta-analysis. Minerva Cardiol Angiol 2024 doi: 10.23736/S2724-5683.24.06505-0.
47.
Hasan SU, Pervez A, Shah AA, et al. Safety outcomes of anti-platelet therapy post coronary artery bypass graft surgery: a systematic review and network meta-analysis of randomized control trials. Perfusion 2024; 39: 684-97.
48.
Agarwal N, Mahmoud AN, Patel NK, et al. Meta-analysis of aspirin versus dual antiplatelet therapy following coronary artery bypass grafting. Am J Cardiol 2018; 121: 32-40.
49.
Shah S, Urtecho M, Firwana M, et al. Perioperative management of antiplatelet therapy: a systematic review and meta-analysis. Mayo Clin Proc Innov Qual Outcomes 2022; 6: 564-73.
50.
Teng R. Ticagrelor: pharmacokinetic, pharmacodynamic and pharmacogenetic profile: an update. Clin Pharmacokinet 2015; 54: 1125-38.
51.
Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373: 723-31.
53.
Jakubowski JA, Winters KJ, Naganuma H, Wallentin L. Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev 2007; 25: 357-74.
54.
Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022; 145: e4-17.
55.
Shuldiner AR, O’Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009; 302: 849-57.
| ISSN: | 2451-0629 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
