Advertisement

American Journal of Cardiovascular Drugs

, Volume 12, Issue 2, pp 83–91 | Cite as

Prasugrel versus Clopidogrel Antiplatelet Therapy after Acute Coronary Syndrome

Matching Treatments with Patients
  • James E. TchengEmail author
  • Steven M. Mackay
Review Article

Abstract

Antithrombotic therapy is imperative in the management of patients presenting with an acute coronary syndrome (ACS). The combination of antiplatelet therapy in conjunction with antithrombotic therapy has become the standard of care in improving the morbidity and mortality of patients with an ACS and in reducing ischemic complications of percutaneous coronary intervention. Patients with an ACS are at increased risk for a recurrent event, both in-hospital and for several months afterward. Secondary prevention to reduce these events is accomplished through the establishment of appropriate medical therapy. Dual antiplatelet therapy with aspirin and adenosine 5′-diphosphate P2Y12 receptor blockers such as ticlopidine or clopidogrel are integral components of this regimen; however, both of these thienopyridines have a relatively slow onset of action and variable bioavailability. Prasugrel, a third-generation thienopyridine approved by the US FDA in 2009, has a more rapid onset of platelet inhibition than clopidogrel and ticlopidine because of increased efficiency of prodrug-to-active metabolite conversion. The result is higher and less variable concentration of the active metabolite within 60 minutes following oral dosing. Phase II and III trials assessing the safety and efficacy of prasugrel have been completed, including JUMBO-TIMI 26, PRINCIPLE-TIMI 44, and TRITON-TIMI 38. These trials demonstrated greater inhibition of platelet aggregation and lower rates of the composite endpoint of death, non-fatal myocardial infarction, and stroke compared with clopidogrel. However, major bleeding occurred more frequently with prasugrel treatment than with clopidogrel. This review highlights the current state of evidence-based antiplatelet therapy and provides guidance on appropriate use of prasugrel in cardiovascular medicine.

Keywords

Percutaneous Coronary Intervention Acute Coronary Syndrome Clopidogrel Stent Thrombosis Ticlopidine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Medical writing assistance was provided by M.K. Grandison, PhD, of Adis Communications, through financial support by Daiichi Sankyo, Inc. and Eli Lilly and Company.

Conflicts of interest: James E. Tcheng has served as a consultant for Daiichi Sankyo, Inc. and Eli Lilly and Company. Dr Tcheng has also received honoraria for serving on the speaker’s bureaus for Daiichi Sankyo, Inc. and Eli Lilly and Company, and Sanofi. Steven M. Mackay is employed and serves on active duty for the United States Naval Medical Corps. Dr Mackay has received CME paid expenses from the US Naval Medical Corps.

Role of the funding source: Preparation of this manuscript was supported by Daiichi Sankyo, Inc. and Eli Lilly and Company.

References

  1. 1.
    Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2003 Jan; 2 (1): 15–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Bhatt DL. Intensifying platelet inhibition: navigating between Scylla and Charybdis. N Engl J Med 2007 Nov 15; 357 (20): 2078–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Barker CM, Price MJ. Antiplatelet therapy in acute coronary syndromes. Curr Cardiol Rep 2008 Jul; 10 (4): 327–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Kushner FG, Hand M, Smith Jr SC, et al. 2009 Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/ AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009 Dec 1; 120 (22): 2271–306.PubMedCrossRefGoogle Scholar
  5. 5.
    Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA Focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011 May 10; 123 (18): 2022–60.PubMedCrossRefGoogle Scholar
  6. 6.
    Steinhubl SR, Tan WA, Foody JM, et al. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. JAMA 1999 Mar 3; 281 (9): 806–10.PubMedCrossRefGoogle Scholar
  7. 7.
    Bertrand ME, Rupprecht HJ, Urban P, et al. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 2000 Aug 8; 102 (6): 624–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Angiolillo DJ, Guzman LA, Bass TA. Current antiplatelet therapies: benefits and limitations. Am Heart J 2008 Aug; 156 (2 Suppl.): S3–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Serebruany VL, Steinhubl SR, Berger PB, et al. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005 Jan 18; 45 (2): 246–51.PubMedCrossRefGoogle Scholar
  10. 10.
    Mega JL, Close SL, Wiviott SD, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009 May 19; 119 (19): 2553–60.PubMedCrossRefGoogle Scholar
  11. 11.
    Giorgi MA, Cohen Arazi H, Gonzalez CD, et al. Beyond efficacy: pharmacokinetic differences between clopidogrel, prasugrel and ticagrelor. Expert Opin Pharmacother 2011 Jun; 12 (8): 1285–95.PubMedCrossRefGoogle Scholar
  12. 12.
    Wiviott SD, Antman EM, Braunwald E. Prasugrel. Circulation 2010 Jul 27; 122 (4): 394–403.PubMedCrossRefGoogle Scholar
  13. 13.
    Roden DM, Stein CM. Clopidogrel and the concept of high-risk pharmacokinetics. Circulation 2009 Apr 28; 119 (16): 2127–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Sugidachi A, Ogawa T, Kurihara A, et al. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel’s active metabolite. J Thromb Haemost 2007 Jul; 5 (7): 1545–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Wallentin L, Varenhorst C, James S, et al. Prasugrel achieves greater and faster P2Y12receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J 2008 Jan; 29 (1): 21–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Payne CD, Li YG, Small DS, et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol 2007 Nov; 50 (5): 555–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Farid NA, Smith RL, Gillespie TA, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos 2007 Jul; 35 (7): 1096–104.PubMedCrossRefGoogle Scholar
  18. 18.
    Niitsu Y, Jakubowski JA, Sugidachi A, et al. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost 2005 Apr; 31 (2): 184–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Wiviott SD, Antman EM, Winters KJ, et al. Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 2005 Jun 28; 111 (25): 3366–73.PubMedCrossRefGoogle Scholar
  20. 20.
    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 Dec 18; 116 (25): 2923–32.PubMedCrossRefGoogle Scholar
  21. 21.
    Wiviott SD, Antman EM, Gibson CM, et al. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J 2006 Oct; 152 (4): 627–35.PubMedCrossRefGoogle Scholar
  22. 22.
    Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007 Nov 15; 357 (20): 2001–15.PubMedCrossRefGoogle Scholar
  23. 23.
    EFFIENT (prasugrel) tablets. US prescribing information. Parsippany (NJ) and Indianapolis (IN): Daiichi Sankyo, Inc. and Eli Lilly and Company, 2010.Google Scholar
  24. 24.
    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 Feb 28; 373 (9665): 723–31.PubMedCrossRefGoogle Scholar
  25. 25.
    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 Oct 14; 118 (16): 1626–36.PubMedCrossRefGoogle Scholar
  26. 26.
    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 Apr 19; 371 (9621): 1353–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Ajani AE, Lefkovits J. Approaching an age of reason with antiplatelet therapy. Lancet 2008 Apr 19; 371 (9621): 1315–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006 Nov 23; 355 (21): 2203–16.PubMedCrossRefGoogle Scholar
  29. 29.
    Subherwal S, Bach RG, Chen AY, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) bleeding score. Circulation 2009 Apr 14; 119 (14): 1873–82.PubMedCrossRefGoogle Scholar
  30. 30.
    Mehta SR, Bassand JP, Chrolavicius S, et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010 Sep 2; 363 (10): 930–42.PubMedCrossRefGoogle Scholar
  31. 31.
    Food and Drug Administration. FDA Drug Safety Communication: reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug. 2010 [online]. Available from URL: http://www.fda.gov/drugs/drugsafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203888.htm [Accessed 2011 Jun 15].
  32. 32.
    Holmes Jr DR, Dehmer GJ, Kaul S, et al. ACCF/AHA Clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation 2010 Aug 3; 122 (5): 537–57.PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.United States Navy, Naval Medical CenterPortsmouthUSA

Personalised recommendations