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Prasugrel vs. Ticagrelor in acute coronary syndromes: Which one to choose?

Prasugrel vs. Ticagrelor beim akuten Koronarsyndrom: Welche Substanz im klinischen Alltag?

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Zusammenfassung

Das akute Koronarsyndrom (ACS) ist immer noch mit einer erheblichen Morbidität und Mortalität assoziiert. In den letzten beiden Dekaden galt die duale Antiplättchentherapie mit Clopidogrel und Azetylsalizylsäure als medikamentöser Therapiestandard bei Patienten mit ACS. Allerdings hat Clopidogrel auch einige Nachteile wie zum Beispiel ein verzögertes Einsetzen des Therapieeffekts, eine bedeutende interindividuelle Variabilität der Plättchenaggregationshemmung sowie eine reduzierte Wirkung auf Thrombozyten aufgrund von Medikamenteninteraktionen oder Einfluss von genetischen Polymorphismen. Aus diesen Gründen wurden neue Thrombozytenaggregationshemmer entwickelt. Zwei Substanzen der neuen Generation, nämlich Prasugrel und Ticagrelor, wurden von der "European Medicines Agency" (EMA) zugelassen und sind bereits in mehreren Europäischen Ländern verfügbar. Beide Medikamente wurden separat in einem "Mega-Trial" im Vergleich zu Clopidogrel untersucht. Beide Substanzen waren eindeutig effektiver hinsichtlich einer Reduktion eines kombinierten ischämischen Endpunktes im Vergleich zu Clopidogrel und sollten laut aktuellen Richtlinien bei Patienten mit ACS bevorzugt eingesetzt werden. Allerdings existiert bisher keine Studie, die die Wirkung und Sicherheit von Prasugrel und Ticagrelor direkt miteinander verglichen hat. In der Praxis steht die/der klinisch tätige Ärztin/Arzt deshalb vor der Entscheidung, welche Substanz sie/er verwenden sollen. Ziel dieses Manuskripts ist es deshalb, einen Überblick über die vorliegende Literatur zu geben und einen Leitfaden in der Entscheidungsfindung zwischen Prasugrel und Ticagrelor bei Patienten mit ACS für den klinischen Alltag zu liefern.

Summary

Acute coronary syndromes (ACS) are still associated with significant morbidity and mortality. Dual antiplatelet therapy with clopidogrel and acetyl-salicylic acid has become the standard of care for patients with ACS in the last 2 decades. However, clopidogrel has drawbacks including delayed therapeutic effect, significant interindividual variability of platelet aggregation inhibition or reduced action on thrombocytes due to interaction with other drugs or genetic polymorphisms. Consequently, new antiplatelet drugs have been developed. Two of these drugs, namely prasugrel and ticagrelor, have been approved by the European Medicines Agency (EMA) and are already available in many European countries. For each substance a "mega-trial" has been published. Both agents were clearly superior compared to clopidogrel and should be therefore preferred in patients with ACS. However, no study has directly compared efficacy as well as safety of prasugrel and ticagrelor so far. Hence, clinicians will be claimed to decide which one to choose in everyday practice. The aim of this manuscript is to summarize the current literature and to provide a guide for individual decision-making between prasugrel and ticagrelor in ACS in daily routine.

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References

  • World Health Organization. Fact sheet No. 317, January 2011. Available at http://www.who.int/mediacentre/factsheets/fs317/en/index.html

  • Widimsky P, Wijns W, Fajadet J, et al. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. Eur Heart J 2010;31(8):943–57

    Article  PubMed  Google Scholar 

  • Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 2010;304:1821–30

    Article  PubMed  CAS  Google Scholar 

  • Yukhanyan L, Freynhofer MK, Siller-Matula J, Schrör K, Huber K. Genetic variability in response to clopidogrel therapy and its clinical implications. Thromb Haemost 2011; [Epub ahead of print]. PMID: 21479337

  • Tentzeris I, Siller-Matula J, Farhan S, Jarai R, Wojta J, Huber K. Platelet function variability and non-genetic causes. Thromb Haemost 2011; [Epub ahead of print]. PMID: 21491057

  • Varenhorst C, James S, Erlinge D, et al. Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease. Eur Heart J 2009;30(14):1744–52

    Article  PubMed  CAS  Google Scholar 

  • Price MJ, Berger PB, Teirstein PS, et al. GRAVITAS investigators. Standard- vs. high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011;305(11):1097–105

    Article  PubMed  CAS  Google Scholar 

  • Huber K. Genetic variability in response to clopidogrel therapy: clinical implications. Eur Heart J 2010;31(24):2974–6

    Article  PubMed  CAS  Google Scholar 

  • Holmes DJ, Dehmer G, Kaul S, Leifer D, O'Gara P, Stein C. 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;122:537–57

    Article  PubMed  Google Scholar 

  • Wiviott SD, Braunwald E, McCabe CH, et al. TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357(20):2001–15

    Article  PubMed  CAS  Google Scholar 

  • 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(11):1045–57

    Article  PubMed  CAS  Google Scholar 

  • European Association for Percutaneous Cardiovascular Interventions, 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(20):2501–55

    Article  PubMed  Google Scholar 

  • Farid NA, Smith RL, Gillespie TA, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos 2007;35(7):1096–104

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa M, Sugidachi A, Ogawa T, Isobe T, Jakubowski JA, Asai F. Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thromb Haemost 2005;94(3):593–8

    PubMed  CAS  Google Scholar 

  • Wiviott SD, Trenk D, Frelinger AL, et al. PRINCIPLE-TIMI 44 Investigators. 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(25):2923–32

    Article  PubMed  CAS  Google Scholar 

  • Wiviott SD, Antman EM, Gibson CM, et al. TRITON-TIMI 38 Investigators. 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;152(4):627–35

    Article  PubMed  CAS  Google Scholar 

  • Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA 2000;284(7):835–42

    Article  PubMed  CAS  Google Scholar 

  • De Luca G, Navarese EP, Cassetti E, Verdoia M, Suryapranata H. Meta-analysis of randomized trials of glycoprotein IIb/IIIa inhibitors in high-risk acute coronary syndromes patients undergoing invasive strategy. Am J Cardiol 2011;107(2):198–203

    Article  PubMed  CAS  Google Scholar 

  • Summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000984/WC500021971.pdf; page 2 and 3

  • Chin CT, Roe MT, Fox KA, et al. TRILOGY ACS Steering Committee. Study design and rationale of a comparison of prasugrel and clopidogrel in medically managed patients with unstable angina/non-ST-segment elevation myocardial infarction: the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage AcuteCoronary Syndromes (TRILOGY ACS) trial. Am Heart J 2010;160(1):16–22

    Article  PubMed  CAS  Google Scholar 

  • Wiviott SD, Braunwald E, Angiolillo DJ, et al. TRITON-TIMI 38 Investigators. 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(16):1626–36

    Article  PubMed  CAS  Google Scholar 

  • 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(21):2028–33

    Article  PubMed  CAS  Google Scholar 

  • Montalescot G, Wiviott SD, Braunwald E, et al. TRITON-TIMI 38 investigators. 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(9665):723–31

    Article  PubMed  CAS  Google Scholar 

  • Murphy SA, Antman EM, Wiviott SD, et al. TRITON-TIMI 38 Investigators. Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial. Eur Heart J 2008;29(20):2473–9

    Article  PubMed  CAS  Google Scholar 

  • Mega JL, Close SL, Wiviott SD, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet 2010;376(9749):1312–9

    Article  PubMed  CAS  Google Scholar 

  • Serebruany VL. Platelet inhibition with prasugrel and increased cancer risks: potential causes and implications. Am J Med 2009;122(5):407–8

    Article  PubMed  Google Scholar 

  • Serebruany VL, Atar D. The PLATO trial: do you believe in magic? Eur Heart J 2010;31(7):764–7

    Article  PubMed  Google Scholar 

  • Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006;27(9):1038–47

    Article  PubMed  CAS  Google Scholar 

  • Cannon CP, Husted S, Harrington RA, et al. DISPERSE-2 Investigators. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol 2007;50(19):1844–51

    Article  PubMed  CAS  Google Scholar 

  • Storey RF, Bliden KP, Patil SB, et al. ONSET/OFFSET Investigators. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol 2010;56(3):185–93

    Article  PubMed  CAS  Google Scholar 

  • James S, Akerblom A, Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J 2009;157(4):599–605

    Article  PubMed  CAS  Google Scholar 

  • Gaglia MA Jr, Waksman R. Overview of the 2010 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee meeting regarding ticagrelor. Circulation 2011;123(4):451–6

    Article  PubMed  Google Scholar 

  • James S, Angiolillo DJ, Cornel JH, et al. PLATO Study Group. 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(24):3006–16

    Article  PubMed  CAS  Google Scholar 

  • Steg PG, James S, Harrington RA, et al. PLATO Study Group. 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(21):2131–41

    Article  PubMed  Google Scholar 

  • James S, Budaj A, Aylward P, et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 2010;122(11):1056–67

    Article  PubMed  Google Scholar 

  • Held C, Asenblad 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(6):672–84

    Article  PubMed  CAS  Google Scholar 

  • Storey RF, Melissa Thornton S, Lawrance R, et al. Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3. Platelets 2009;20(5):341–8

    Article  PubMed  CAS  Google Scholar 

  • Wallentin L, James S, Storey RF, et al. PLATO investigators. 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 2010;376(9749):1320–8

    Article  PubMed  CAS  Google Scholar 

  • Summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001241/WC500100494.pdf; page 5 and 11

  • 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 2010; [Epub ahead of print]

  • Mehran R, Pocock SJ, Nikolsky E, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol 2010;55(23):2556–66

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Univ.-Clinic of Internal Medicine III – Cardiology, Innsbruck Medical University, Innsbruck, Austria

    Hannes F. Alber, Otmar Pachinger & Matthias Frick

  2. 3rd Department of Medicine, Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria

    Kurt Huber

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  1. Hannes F. Alber
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  2. Kurt Huber
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Correspondence to Matthias Frick.

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Alber, H., Huber, K., Pachinger, O. et al. Prasugrel vs. Ticagrelor in acute coronary syndromes: Which one to choose?. Wien Klin Wochenschr 123, 468–476 (2011). https://doi.org/10.1007/s00508-011-0027-7

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