Skip to main content
SpringerLink
Log in

Differential Use of Glycoprotein IIb/IIIa Inhibitors with Bivalirudin in Patients with STEMI Undergoing PCI: A Systematic Review and Meta-Analysis

  • Systematic Review
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Aim

The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI.

Methods

Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs).

Results

When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72–0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57–0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66–0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72–0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13–2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24–0.65; P = 0.0003).

Conclusion

Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Corbett SJ, Ftouh S, Lewis S et al. Acute coronary syndromes: summary of updated NICE guidance. BMJ 2021;372, DOI: https://doi.org/10.1136/BMJ.M4760.

  2. Jafary FH. Anticoagulants and Primary PCI. Primary Angioplasty 2018:109–18.

  3. Roffi M, Patrono C, Collet J-P, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267–315.

    Article  CAS  PubMed  Google Scholar 

  4. Ibanez B, James S, Agewall S, et al. 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;39:119–77.

    Article  PubMed  Google Scholar 

  5. Collet J-P, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevationThe Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2021;42:1289–367.

    Article  PubMed  Google Scholar 

  6. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during Primary PCI in Acute Myocardial Infarction. N Engl J Med. 2008;358:2218–30.

    Article  CAS  PubMed  Google Scholar 

  7. Shahzad A, Kemp I, Mars C, et al. Unfractionated heparin versus Bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): An open-label, single centre, randomised controlled trial. The Lancet. 2014;384:1849–58.

    Article  CAS  Google Scholar 

  8. James S, Koul S, Andersson J, et al. Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction. Circ Cardiovasc Interv. 2021;14:E008969.

    Article  CAS  PubMed  Google Scholar 

  9. Li Y, Liang Z, Qin L, et al. Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial. Lancet. 2022;400:1847–57.

    Article  CAS  PubMed  Google Scholar 

  10. Capodanno D, Gargiulo G, Capranzano P, et al. Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary PCI: An updated meta-analysis of 10,350 patients from five randomized clinical trials. Eur Heart J Acute Cardiovasc Care. 2016;5:253–62.

    Article  PubMed  Google Scholar 

  11. Liu XQ, Luo X Du, Wu YQ et al. Efficacy and safety of bivalirudin vs heparin in patients with coronary heart disease undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials. Medicine (United States) 2020;99, DOI: https://doi.org/10.1097/MD.0000000000019064.

  12. Page MJ, McKenzie JE, The BPM, PRISMA, et al. statement: an updated guideline for reporting systematic reviews. BMJ. 2020;2021:372. https://doi.org/10.1136/BMJ.N71.

    Article  Google Scholar 

  13. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.

  14. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Steg PG, van ’t Hof A, Hamm CW et al. Bivalirudin Started during Emergency Transport for Primary PCI. New England Journal of Medicine 2013;369:2207–17.

  16. Leonardi S, Frigoli E, Rothenbühler M et al. Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial. BMJ 2016;354, DOI: https://doi.org/10.1136/BMJ.I4935.

  17. Wang H, Li Y, Cong H, et al. Efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access: A subgroup analysis from the bivalirudin in acute myocardial infarction versus heparin and GPI plus heparin trial. Catheter Cardiovasc Interv. 2017;89:1157–65.

    Article  PubMed  Google Scholar 

  18. Schulz S, Richardt G, Laugwitz K-L et al. Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction. Eur Heart J 2014;35:2285–94.

  19. Alexander W. Bivalirudin Versus Heparin: A Fight Far From Finished?: Efficacy, Safety, and Cost Remain Battlegrounds for the Treatment Of ST-Segment Elevation Myocardial Infarction. Pharmacy and Therapeutics. 2015;40:209.

    PubMed  PubMed Central  Google Scholar 

  20. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355:2203–16.

    Article  CAS  PubMed  Google Scholar 

  21. Kastrati A, Neumann F-J, Schulz S, et al. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med. 2011;365:1980–9.

    Article  PubMed  Google Scholar 

  22. Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic complications of anticoagulant treatment. Chest. 2001;119:108S-121S.

    Article  CAS  PubMed  Google Scholar 

  23. Berlioz BE, Sanghavi DK. Bivalirudin. StatPearls 2023.

  24. Gladwell TD. Bivalirudin: a direct thrombin inhibitor. Clin Ther. 2002;24:38–58.

    Article  CAS  PubMed  Google Scholar 

  25. Andreou C, Maniotis C, Koutouzis M. The Rise and Fall of Anticoagulation with Bivalirudin During Percutaneous Coronary Interventions: A Review Article. Cardiol Ther. 2017;6:1–12.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Warkentin TE, Greinacher A, Koster A. Bivalirudin. Thromb Haemost. 2008;99:830–9.

    Article  CAS  PubMed  Google Scholar 

  27. Lee CJ, Ansell JE. Direct thrombin inhibitors. Br J Clin Pharmacol. 2011;72:581–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Clemmensen P, Wiberg S, Van’T Hof A et al. Acute stent thrombosis after primary percutaneous coronary intervention: insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography). JACC Cardiovasc Interv 2015;8:214–20.

  29. Jagadish PS, Le FK, Labroo A, et al. A Meta-analysis of Clinical Trials Evaluating the Impact of Bivalirudin-based Anticoagulation for Primary Percutaneous Coronary on Long-Term Mortality. J Cardiovasc Pharmacol. 2021;78:E40–4.

    Article  CAS  PubMed  Google Scholar 

  30. Mehran R, Lansky AJ, Witzenbichler B, et al. Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial. Lancet. 2009;374:1149–59.

    Article  PubMed  Google Scholar 

  31. Nathan S, Rao SV. Radial versus femoral access for percutaneous coronary intervention: implications for vascular complications and bleeding. Curr Cardiol Rep. 2012;14:502–9.

    Article  PubMed  Google Scholar 

  32. Kent DM, Rothwell PM, Ioannidis JPA et al. Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials 2010;11, DOI: https://doi.org/10.1186/1745-6215-11-85.

  33. Wang X, Piantadosi S, Le-Rademacher J, et al. Statistical Considerations for Subgroup Analyses. J Thorac Oncol. 2021;16:375–80. https://doi.org/10.1016/j.jtho.2020.12.008.

    Article  PubMed  Google Scholar 

  34. Burke JF, Sussman JB, Kent DM et al. Three simple rules to ensure reasonably credible subgroup analyses. BMJ 2015;351. DOI: https://doi.org/10.1136/bmj.h5651.

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan

    Hasan Mushahid, Syeda Ayesha Shah, Syed Husain Farhan, Muhammad Hamza Shuja, Asad Ali Siddiqui & Ishaque Hameed

  2. Edinburgh School of Medicine, University of Edinburgh, Edinburgh, UK

    Kyle Balasingam

  3. Orlando Health Heart and Vascular Institute, Orlando, FL, USA

    Kamran Akram

  4. Department of Medicine, The Dudley Group NHS Foundation Trust, Dudley, UK

    Shayan Mushahid

  5. Department of Internal Medicine, University of Texas Southwestern Medical Center, Texas, Dallas, USA

    Muhammad Shariq Usman

Authors
  1. Hasan Mushahid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syeda Ayesha Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Syed Husain Farhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muhammad Hamza Shuja
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kyle Balasingam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Asad Ali Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ishaque Hameed
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kamran Akram
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shayan Mushahid
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Muhammad Shariq Usman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shayan Mushahid.

Ethics declarations

Conflicts of interest

Hasan Mushahid, Syeda Ayesha Shah, Syed Husain Farhan, Muhammad Hamza Shuja, Kyle Balasingam, Asad Ali, Ishaque Hameed, Kamran Akram, Shayan Mushahid, and Muhammad Shariq Usman declare that they have no potential conflicts of interest that might be relevant to the contents of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Code availability

Not applicable.

Data availability

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials.

Authors’ contributions

HM: Conceptualization; investigation; formal analysis; writing – original draft; writing – review and editing. SAS: Conceptualization; investigation; formal analysis; writing – original draft. SHF: Formal analysis; methodology. MHS: Methodology; writing – original draft. KB: Methodology; writing – original draft. AA: Writing – review and editing. IH: Resources; writing – review and editing; project administration. KA: Project administration; supervision. SM: Project administration; supervision. MSU: Methodology; writing – review and editing; project administration.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 970 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mushahid, H., Shah, S.A., Farhan, S.H. et al. Differential Use of Glycoprotein IIb/IIIa Inhibitors with Bivalirudin in Patients with STEMI Undergoing PCI: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs 24, 385–398 (2024). https://doi.org/10.1007/s40256-024-00636-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-024-00636-6

Search

Navigation