Cardiovascular Drugs and Therapy

, Volume 27, Issue 3, pp 239–245 | Cite as

Dual Antiplatelet Therapy with Prasugrel or Ticagrelor Versus Clopidogrel in Interventional Cardiology

  • Peter Clemmensen
  • Nadia Paarup Dridi
  • Lene Holmvang
REVIEW ARTICLE

Abstract

For several years, clopidogrel plus aspirin has been the dual antiplatelet therapy (DAPT) of choice for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation. More recently, prasugrel and ticagrelor have demonstrated greater efficacy than clopidogrel. In TRITON-TIMI 38, the risk of TIMI major bleeding unrelated to coronary artery bypass graft (CABG) surgery was similar for prasugrel and clopidogrel after excluding subgroups with increased bleeding risk (previous stroke or transient ischemic event; age ≥75 years; weight <60 kg). In the PLATO trial, rates of TIMI major bleeding were similar for ticagrelor and clopidogrel, but ticagrelor was associated with a significantly higher rate of non-CABG-related TIMI major bleeding. Current evidence suggests that prasugrel or ticagrelor plus aspirin should be the DAPT of choice in patients with ACS undergoing PCI unless they are at particularly high risk of bleeding. No studies have yet compared prasugrel and ticagrelor in ACS patients, however prasugrel and ticagrelor have different side effect profiles, and the choice of agent should be made either as a default choice and/or on an individual patient basis. Ongoing trials in ACS patients will increase the evidence base for new P2Y12 receptor inhibitors and help to establish the most effective DAPT regimens.

Keywords

Acute coronary syndrome Clopidogrel Dual antiplatelet therapy Percutaneous coronary intervention Prasugrel Ticagrelor 

Notes

Acknowledgments

The authors would like to acknowledge the assistance of Sarah Whitfield, medical writer, and Springer Healthcare Ltd in the preparation of this manuscript, supported by a grant from Daiichi Sankyo Europe GmbH and Eli Lilly and Company. The authors are responsible for the final version of the review.

Conflicts of Interest

Peter Clemmensen has previously or currently been involved in research contracts, consulting, speakers bureau or received research and educational grants from:
  • Abbott, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli-Lilly, Evolva, Fibrex, Merck, Myogen, Medtronic, Mitsubishi Pharma, The Medicines Company, Nycomed, Organon, Pfizer, Pharmacia, Sanofi, Searle, and Servier.

  • Lene Holmvang has received speaker honoraria from AstraZeneca, Bayer AG, Daiichi-Sankyo Europe GmbH and Eli Lilly and Company, and consulting fees from AstraZeneca, Bristol-Myers Squibb and Eli Lilly and Company.

References

  1. 1.
    Wijns W, Kolh P, Danchin N, et al. 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). Eur Heart J. 2010;31:2501–55.PubMedCrossRefGoogle Scholar
  2. 2.
    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.PubMedCrossRefGoogle Scholar
  3. 3.
    Testa L, Biondi Zoccai GG, Valgimigli M, et al. Current concepts on antiplatelet therapy: focus on the novel thienopyridine and non-thienopyridine agents. Adv Hematol. 2010;2010:595934.PubMedGoogle Scholar
  4. 4.
    Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.PubMedCrossRefGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    Mahaffey KW, Wojdyla DM, Carroll K, et al. PLATO Investigators. Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) Trial. Circulation. 2011;124:544–54.PubMedCrossRefGoogle Scholar
  7. 7.
    Roe MT, Armstrong PW, Fox KAA, et al. TRILOGY ACS Investigators. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367:1297–309.PubMedCrossRefGoogle Scholar
  8. 8.
    Bellemain-Appaix A, Brieger D, Beygui F, et al. New P2Y12 inhibitors versus clopidogrel in percutaneous coronary intervention: a meta-analysis. J Am Coll Cardiol. 2010;56:1542–51.PubMedCrossRefGoogle Scholar
  9. 9.
    Biondi-Zoccai G, Lotrionte M, Agostoni P, et al. Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes. Int J Cardiol. 2011;150:325–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Steg PG, James S, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: a Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation. 2010;122:2131–41.PubMedCrossRefGoogle Scholar
  11. 11.
    Koul S, Smith JG, Scherstén F, James S, Lagerqvist B, Erlinge D. Effect of upstream clopidogrel treatment in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J. 2011;32:2989–97.PubMedCrossRefGoogle Scholar
  12. 12.
    Dörler J, Edlinger M, Alber HF, et al. Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction. Eur Heart J. 2011;32:2954–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Wallentin L, Becker RC, Budaj A, et al. PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–57.PubMedCrossRefGoogle Scholar
  14. 14.
    De Servi S, Navarese EP, D’Urbano M, Savonitto S. Treating acute coronary syndromes with new antiplatelet drugs: the mortality issue with prasugrel and ticagrelor. Curr Med Res Opin. 2011;27:2117–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Sabatine MS, Hamdalla HN, Mehta SR, et al. Efficacy and safety of clopidogrel pretreatment before percutaneous coronary intervention with and without glycoprotein IIb/IIIa inhibitor use. Am Heart J. 2008;155:910–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Hamm CW, Bassand J-P, Agewall S, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011;32:2999–3054.PubMedCrossRefGoogle Scholar
  17. 17.
    Angiolillo DJ, Badimon JJ, Saucedo JF, et al. A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 trial. Eur Heart J. 2011;32:838–46.PubMedCrossRefGoogle Scholar
  18. 18.
    Ferreiro JL, Angiolillo DJ. Diabetes and antiplatelet therapy in acute coronary syndrome. Circulation. 2011;123:798–813.PubMedCrossRefGoogle Scholar
  19. 19.
    Wiviott SD, Braunwald E, Angiolillo DJ, et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel—thrombolysis in myocardial infarction 38. Circulation. 2008;118:1626–36.PubMedCrossRefGoogle Scholar
  20. 20.
    James S, Angiolillo DJ, Cornel JH, et al. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J. 2010;31:3006–16.PubMedCrossRefGoogle Scholar
  21. 21.
    Wiviott SD, Braunwald E, McCabe CH, et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet. 2008;371:1353–63.PubMedCrossRefGoogle Scholar
  22. 22.
    Antman EM, Wiviott SD, Murphy SA, et al. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel—thrombolysis in myocardial infarction) analysis. J Am Coll Cardiol. 2008;51:2028–33.PubMedCrossRefGoogle Scholar
  23. 23.
    Wiviott SD, Trenk D, Frelinger AL, et al. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the prasugrel in comparison to clopidogrel for inhibition of platelet activation and aggregation—thrombolysis in myocardial infarction 44 trial. Circulation. 2007;116:2923–32.PubMedCrossRefGoogle Scholar
  24. 24.
    Becker RC, Bassand JP, Budaj A, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient outcomes (PLATO) trial. Eur Heart J. 2011;32:2933–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Angiolillo DJ, Saucedo JF, DeRaad R, et al. Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes: results of the SWAP (SWitching Anti Platelet) study. J Am Coll Cardiol. 2010;56:1017–23.PubMedCrossRefGoogle Scholar
  26. 26.
    Montalescot G, Sideris G, Cohen R, et al. Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study. Thromb Haemost. 2010;103:213–23.PubMedCrossRefGoogle Scholar
  27. 27.
    Alexopoulos D, Galati A, Xanthopoulou I, et al. Ticagrelor versus prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following percutaneous coronary intervention: a pharmacodynamic study. J Am Coll Cardiol. 2012;60:193–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Trenk D, Stone GW, Gawaz M, et al. 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. 2012;59:1259–64.CrossRefGoogle Scholar
  29. 29.
    Mahoney EM, Wang K, Arnold SV, et al. Cost-effectiveness of prasugrel versus clopidogrel in patients with acute coronary syndromes and planned percutaneous coronary intervention: results from the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel—thrombolysis in myocardial infarction TRITON-TIMI 38. Circulation. 2010;121:71–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Crespin DJ, Federspiel JJ, Biddle AK, Jonas DE, Rossi JS. Ticagrelor versus genotype-driven antiplatelet therapy for secondary prevention after acute coronary syndrome: a cost-effectiveness analysis. Value Health. 2011;14:483–91.PubMedCrossRefGoogle Scholar
  31. 31.
    Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296–310.PubMedCrossRefGoogle Scholar
  32. 32.
    Efient: Summary of product characteristics. 2011. http://www.medicines.org.uk/emc/medicine/21504/SPC. Accessed 6 April 2012.
  33. 33.
    Schuler J, Maier B, Behrens S, Thimme W. Present treatment of acute myocardial infarction in patients over 75 years: data from the Berlin Myocardial Infarction Registry (BHIR). Clin Res Cardiol. 2006;95:360–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Brilique summary of product characteristics. 2011. http://www.medicines.org.uk/emc/medicine/23935/SPC. Accessed 6 April 2012.
  35. 35.
    Held C, Åsenblad 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.PubMedCrossRefGoogle Scholar
  36. 36.
    Angiolillo DJ, Firstenberg MS, Price MJ, et al. BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012;307:265–74.PubMedCrossRefGoogle Scholar
  37. 37.
    Sørensen R, Hansen ML, Abildstrom SZ, et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet. 2009;374:1967–74.PubMedCrossRefGoogle Scholar
  38. 38.
    Lip GY, Huber K, Andreotti F, et al. Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: executive summary—a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2010;31:1311–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Peter Clemmensen
    • 1
  • Nadia Paarup Dridi
    • 1
  • Lene Holmvang
    • 1
  1. 1.Department of Cardiology B, The Heart CentreRigshospitalet - Copenhagen University HospitalCopenhagenDenmark

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