Thromb Haemost 2022; 122(11): 1879-1887
DOI: 10.1055/a-1853-2952
New Technologies, Diagnostic Tools and Drugs

Clopidogrel Monotherapy versus Aspirin Monotherapy in Patients with Established Cardiovascular Disease: Systematic Review and Meta-Analysis

1   Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
,
Ioannis G. Kyriakoulis
1   Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
,
Dimitrios Sagris
1   Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
,
Hans Christoph Diener
2   Department of Neuroepidemiology, University of Duisburg-Essen, Essen, Germany
,
George Ntaios
1   Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
› Author Affiliations
Funding None.


Abstract

Background There is no clear consensus on whether aspirin offers better outcomes in terms of secondary cardiovascular disease prevention compared with clopidogrel.

Objective The aim of the study was to compare the safety and efficacy of clopidogrel versus aspirin in patients with established cardiovascular disease.

Methods A systematic review of MEDLINE (via PubMed), Scopus, and Cochrane Library databases (last search date: August 28, 2021) was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement for randomized control trials (RCTs) of clopidogrel versus aspirin as monotherapy in patients with established cardiovascular disease. Random-effects meta-analyses were performed.

Results Five RCTs incorporating 26,855 patients (clopidogrel: 13,426; aspirin: 13,429) were included. No statistically significant difference was observed between clopidogrel and aspirin in terms of all-cause mortality (odds ratio [OR]: 1.01 [95% confidence interval, CI: 0.91–1.13]; p = 0.83), ischemic stroke (OR: 0.87 [95% CI: 0.71–1.06]; p = 0.16), and major bleeding rates (OR: 0.77 [95% CI: 0.56–1.06]; p = 0.11). Patients receiving clopidogrel had borderline lower risk for major adverse cardiovascular events (MACE) (OR: 0.84 [95% CI: 0.71–1.00]; p = 0.05) and lower risk for nonfatal myocardial infarction (OR: 0.83 [95% CI: 0.71–0.97]; p = 0.02, relative risk reduction = 16.9%, absolute risk reduction = 0.5%, number needed to treat = 217 for a mean period of 20 months) compared with patients receiving aspirin.

Conclusion In patients with established cardiovascular disease, clopidogrel was associated with a 17% relative-risk reduction for nonfatal MI, borderline decreased risk for MACE, and similar risk for all-cause mortality, stroke, and major bleeding compared with aspirin.

Protocol Registration PROSPERO CRD42021283866.

Author Contributions

P.T.T.: responsible for acquisition of data, analysis and interpretation, as well as preparation of the article. I.G.K.: helped in acquisition of data, analysis and interpretation, and critical revision of the article for important intellectual content. D.S.: contributed toward acquisition of data, analysis and interpretation, and critical revision of the article for important intellectual content. H.C.D.: responsible for critical revision of the article for important intellectual content. G.N.: responsible for study concept and design, preparation of the article, and study supervision.


Supplementary Material



Publication History

Received: 18 January 2022

Accepted: 14 May 2022

Accepted Manuscript online:
16 May 2022

Article published online:
31 July 2022

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  • References

  • 1 Visseren FLJ, Mach F, Smulders YM. et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2021; 42: 3227-3337
  • 2 Kleindorfer DO, Towfighi A, Chaturvedi S. et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: a guideline from the American Heart Association/American Stroke Association. Stroke 2021; 52 (07) e364-e467
  • 3 Knuuti J, Wijns W, Saraste A. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020; 41 (03) 407-477
  • 4 Aboyans V, Ricco J-B, Bartelink MEL. et al; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal. Eur Heart J 2018; 39 (09) 763-816
  • 5 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
  • 6 Aggarwal D, Bhatia K, Chunawala ZS. et al. P2Y12 inhibitor versus aspirin monotherapy for secondary prevention of cardiovascular events: meta-analysis of randomized trials. Eur Heart J Open 2022; 2 (02) oeac019
  • 7 Chiarito M, Sanz-Sánchez J, Cannata F. et al. Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis. Lancet 2020; 395 (10235): 1487-1495
  • 8 Kuno T, Ueyama H, Takagi H, Bangalore S. P2Y12 inhibitor monotherapy versus aspirin monotherapy after short-term dual antiplatelet therapy for percutaneous coronary intervention: insights from a network meta-analysis of randomized trials. Am Heart J 2020; 227: 82-90
  • 9 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
  • 10 Patrono C, Morais J, Baigent C. et al. Antiplatelet agents for the treatment and prevention of coronary atherothrombosis. J Am Coll Cardiol 2017; 70 (14) 1760-1776
  • 11 CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348 (9038): 1329-1339
  • 12 Koo B-K, Kang J, Park KW. et al; HOST-EXAM investigators. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet 2021; 397 (10293): 2487-2496
  • 13 Massie BM, Collins JF, Ammon SE. et al; WATCH Trial Investigators. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation 2009; 119 (12) 1616-1624
  • 14 Pettersen A-ÅR, Seljeflot I, Abdelnoor M, Arnesen H. High on-aspirin platelet reactivity and clinical outcome in patients with stable coronary artery disease: results from ASCET (Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial). J Am Heart Assoc 2012; 1 (03) e000703
  • 15 Woodward M, Lowe GDO, Francis LMA, Rumley A, Cobbe SM. CADET Study Investigators. A randomized comparison of the effects of aspirin and clopidogrel on thrombotic risk factors and C-reactive protein following myocardial infarction: the CADET trial. J Thromb Haemost 2004; 2 (11) 1934-1940
  • 16 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71
  • 17 Wohlin C. Guidelines for snowballing in systematic literature studies and a replication in software engineering. In: ACM International Conference Proceeding Series New York, NY: ACM. 2014 38:1–38:10
  • 18 Sterne JAC, Savović J, Page MJ. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898
  • 19 Chapter 14: Completing 'Summary of findings' tables and grading the certainty of the evidence. Cochrane Training [Internet]. [cited 2021 Sep 24]. Accessed May 30, 2022 at: https://training.cochrane.org/handbook/current/chapter-14
  • 20 Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 2012; 379 (9826): 1591-1601
  • 21 Rothwell PM, Fowkes FGR, Belch JFF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377 (9759): 31-41
  • 22 Galiuto L, Patrono C. Challenging the role of aspirin for long-term antiplatelet therapy?. Eur Heart J 2021; 42 (30) 2883-2884
  • 23 Chi N-F, Wen C-P, Liu C-H. et al; Taiwan Stroke Registry Investigators. Comparison between aspirin and clopidogrel in secondary stroke prevention based on real-world data. J Am Heart Assoc 2018; 7 (19) e009856
  • 24 Hankey GJ, Sudlow CL, Dunbabin DW. Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials. Stroke 2000; 31 (07) 1779-1784
  • 25 Paciaroni M, Ince B, Hu B. et al. Benefits and risks of clopidogrel vs. aspirin monotherapy after recent ischemic stroke: a systematic review and meta-analysis. Cardiovasc Ther 2019; 2019: 1607181