Skip to main content
SpringerLink
Log in

Current antiplatelet agents: place in therapy and role of genetic testing

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Antiplatelet therapies play a central role in reducing the risk of cardiovascular events such as myocardial infarction and stroke. While aspirin, a cyclo-oxygenase-1 inhibitor has been the cornerstone of antithrombotic treatment for several decades, P2Y12 receptor inhibitors cangrelor, clopidogrel, prasugrel, and ticagrelor and protease-activated receptor-1 antagonist vorapaxar, have emerged as additional therapies to reduce the risk of recurrent cardiovascular events in high-risk patients. Recent clinical trials evaluating the role of these agents and major society guideline updates for use of antiplatelet therapies for secondary prevention of cardiovascular events will be examined. The latest studies regarding the appropriate duration of dual antiplatelet therapy after percutaneous coronary intervention will be presented. The current state of genetic and platelet function testing will be reviewed.

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

Similar content being viewed by others

References

  1. Go A, Mozaffarian D et al (2013) Heart disease and stroke statistics—2014 update. A report from the American Heart Association. Circulation 129:e28–e292

    Article  PubMed  Google Scholar 

  2. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2(1988) ISIS-2 (Second International Study of Infarct Survival) collaborative group. Lancet. 2:349–360

  3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 204958. FDA Briefing Document for the Cardiovascular and Renal Drugs Advisory Committee. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM385234.pdf Accessed 29 Nov 2014

  4. Food and Drug Administration (2014). FDA approves Zontivity to reduce the risk of heart attacks and stroke in high-risk patients. Retrieved from http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm396585.htm

  5. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK (2001) 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 345:494–502

    Article  CAS  PubMed  Google Scholar 

  6. Matetzky S, Shenkman B, Guetta V et al (2004) Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 109:3171–3175

    Article  CAS  PubMed  Google Scholar 

  7. Gurbel PA, Bliden KP, Hiatt BL, O’Connor CM (2003) Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 107:2908–2913

    Article  PubMed  Google Scholar 

  8. Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, Huber K, EPA (European Platelet Academy) (2013) Response variability to P2Y12 receptor inhibitors: expectations and reality. JAMA Cardiovasc Interv 6:1111–1128

    Article  Google Scholar 

  9. Ikeda Y, Shimada K, Teramoto T et al (2014) Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA 312(23):2510–2520. doi:10.1001/jama.2014.15690

    Article  CAS  PubMed  Google Scholar 

  10. Bayer (2000) A Study to Assess the Efficacy and Safety of Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2014 Nov 27]. Available from: http://clinicaltrials.gov/show/ NCT00501059 NLM Identifier: NCT00501059

  11. University of Oxford (2000) ASCEND: A Study of Cardiovascular Events iN Diabetes. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2014 Nov 27]. Available from: http://clinicaltrials.gov/show/ NCT00135226 NLM Identifier: NCT00135226

  12. Minneapolis Medical Research Foundation (2000) Aspirin in Reducing Events in the Elderly (ASPREE). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2014 Nov 27]. Available from: http://clinicaltrials.gov/show/ NCT01038583 NLM Identifier: NCT01038583

  13. Bhatt DL, Lincoff AM, Gibson CM et al (2009) Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 361(24):2330–2341

    Article  CAS  PubMed  Google Scholar 

  14. Harrington RA, Stone GW, McNulty S et al (2009) Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 361:2318–2329

    Article  CAS  PubMed  Google Scholar 

  15. Bhatt DL, Stone GW, Mahaffey KW et al (2013) Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 368:1303–1313

    Article  CAS  PubMed  Google Scholar 

  16. Angiolillo DJ, Firstenberg MS, Price MJ et al (2012) Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 307:265–274

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Mauri L, Hsieh WH, Massaro JM, Ho KK, D’Agostino R, Cutlip DE (2007) Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 356:1020–1029

    Article  CAS  PubMed  Google Scholar 

  18. Levine GN, Bates ER, Blankenship JC et al (2011) 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 124:e574–e651 (Erratum, Circulation 2012;125(8):e142)

    Article  PubMed  Google Scholar 

  19. Windecker S, Kolh P, Alfonso F et al (2014) 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 35:2541–2619

    Article  PubMed  Google Scholar 

  20. Eisenstein EL, Anstrom KJ, Kong DF et al (2007) Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 297:159–168

    Article  CAS  PubMed  Google Scholar 

  21. Valgimigli M, Campo G, Monti M et al (2012) Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation 125:2015–2026

    Article  CAS  PubMed  Google Scholar 

  22. Park S-J, Park D-W, Kim Y-H et al (2010) Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 362:1374–1382

    Article  CAS  PubMed  Google Scholar 

  23. Feres F, Costa RA, Abizaid A et al (2013) Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA 310:2510–2522

    CAS  PubMed  Google Scholar 

  24. Mauri L, Kereiakes DJ, Yeh RW et al (2014) Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 371:2155–2166 (Epub 2014 Nov 16)

    Article  CAS  PubMed  Google Scholar 

  25. Schulz-Schüpke S (2014) Randomized, double-blind trial of 6 versus 12 months of dual antiplatelet therapy after DES implantation (ISAR-SAFE). Presented at: American Heart Association Scientific Sessions; Chicago, IL

  26. Gilard M, Barragan P, Noryani AA et al (2014) Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial. J Am Coll Cardiol pii:S0735-1097(14)06970-8. doi:10.1016/j.jacc.2014.11.008 (Epub ahead of print)

    Google Scholar 

  27. O’Gara PT, Kushner FG, Ascheim DD et al (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61:485–510

    Article  PubMed  Google Scholar 

  28. Amsterdam EA, Wenger NK, Brindis RG et al (2014) 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol pii:S0735-1097(14)06279-2. doi:10.1016/j.jacc.2014.09.017 (Epub ahead of print)

    Google Scholar 

  29. Brener SJ, Oldroyd KG, Maehara A, El-Omar M, Witzenbichler B, Xu K, Mehran R, Gibson CM, Stone GW (2014) Outcomes in patients with ST-segment elevation acute myocardial infarction treated with clopidogrel versus prasugrel (from the INFUSE-AMI trial). Am J Cardiol 113:1457–1460

    Article  PubMed  Google Scholar 

  30. Henry TD, Peterson E, Cohen D et al (2014) TCT-494 Safety and Effectiveness of Prasugrel vs. Clopidogrel in the Setting of Bivalirudin vs. Heparin Use: 30-day Results from TRANSLATE-ACS. J Am Coll Cardiol 64(11):B145–B146. doi:10.1016/j.jacc.2014.07.548 (ISSN 0735-1097)

    Article  Google Scholar 

  31. Deutsches Herzzentrum Muenchen (2000) Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome (ISAR-REACT 5). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2014 Nov 28]. Available from: http://clinicaltrials.gov/show/ NCT01944800 NLM Identifier: NCT01944800

  32. Lindholm D, Varenhorst C, Cannon CP, Harrington RA, Himmelmann A, Maya J, Husted S, Steg PG, Cornel JH, Storey RF, Stevens SR, Wallentin L, James SK (2014) Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. Eur Heart J 35:2083–2093

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Montalescot G, van’t Hof AW, Lapostolle F et al (2014) Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 371:1016–1027

    Article  CAS  PubMed  Google Scholar 

  34. AstraZeneca (2000) A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Available from: http://clinicaltrials.gov/ct2/show/NCT01732822 NLM Identifier: NCT01732822

  35. AstraZeneca (2000) Prevention of Cardiovascular Events (eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke) in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin (PEGASUS). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Available from: http://clinicaltrials.gov/ct2/show/ NCT01225562 NLM Identifier: NCT01225562

  36. AstraZeneca (2000) SOCRATES -Acute Stroke Or Transient IsChaemic Attack TReated With Aspirin or Ticagrelor and Patient OutcomES. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Available from: http://clinicaltrials.gov/ct2/show/ NCT01994720 NLM Identifier: NCT01994720

  37. AstraZeneca (2000) A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus (THEMIS). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Available from: http://clinicaltrials.gov/ct2/show/ NCT01991795 NLM Identifier: NCT01991795

  38. AstraZeneca (2014). AstraZeneca announces initiation of development programme for BRILINTA® reversal agent [Press release]. Retrieved from http://www.astrazeneca.com/Media/Press-releases/Article/13112014--astrazeneca-announces-initiation-of-development-progr

  39. Tricoci P, Huang Z, Held C et al (2012) Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 366:20–33

    Article  CAS  PubMed  Google Scholar 

  40. Morrow DA, Braunwald E, Bonaca MP et al (2012) Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 366:1404–1413

    Article  CAS  PubMed  Google Scholar 

  41. Valgimigli M, Tricoci P, Huang Z et al (2014) Usefulness and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (from the TRACER Trial). Am J Cardiol 114:665–673

    Article  CAS  PubMed  Google Scholar 

  42. Collet JP, Hulot JS, Pena A et al (2009) Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 373:309–317

    Article  CAS  PubMed  Google Scholar 

  43. Hulot JS, Collet JP, Cayla G et al (2011) CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv 4:422–428

    Article  CAS  PubMed  Google Scholar 

  44. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias WL, Braunwald E, Sabatine MS (2009) Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 119:2553–2560

    Article  CAS  PubMed  Google Scholar 

  45. Wallentin L, James S, Storey RF et al (2010) Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 376(9749):1320–1328

    Article  CAS  PubMed  Google Scholar 

  46. Collet JP, Cuisset T, Rangé G et al (2012) Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 367:2100–2109

    Article  CAS  PubMed  Google Scholar 

  47. Price MJ, Berger PB, Teirstein PS et al (2011) Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 305:1097–1105

    Article  CAS  PubMed  Google Scholar 

  48. Trenk D, Stone GW, Gawaz M et al (2012) A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study. J Am Coll Cardiol 59:2159–2164

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, University of Washington Medical Center, 1959 NE Pacific Street, Box 365005, Seattle, WA, 98195, USA

    Eugene Yang

Authors
  1. Eugene Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eugene Yang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, E. Current antiplatelet agents: place in therapy and role of genetic testing. J Thromb Thrombolysis 39, 328–336 (2015). https://doi.org/10.1007/s11239-015-1195-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-015-1195-5

Keywords

Search

Navigation