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Prasugrel vs ticagrelor in acute coronary syndromes

Prasugrel vs ticagrelor in acute coronary syndromes. Giuseppe Biondi-Zoccai , MD Sapienza University of Rome , Italy giuseppe.biondizoccai@uniroma1.it. Learning goals. Scope of the problem Prasugrel Ticagrelor Reconciling the evidence. Learning goals. Scope of the problem

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Prasugrel vs ticagrelor in acute coronary syndromes

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  1. Prasugrel vs ticagrelor in acute coronary syndromes Giuseppe Biondi-Zoccai, MD Sapienza University ofRome, Italy giuseppe.biondizoccai@uniroma1.it

  2. Learninggoals • Scope of the problem • Prasugrel • Ticagrelor • Reconciling the evidence

  3. Learninggoals • Scope of the problem • Prasugrel • Ticagrelor • Reconciling the evidence

  4. The platelet: our common foe PAR inhibitors Anticoagulants <- <- Aspirin <- P2Y12 inhibitors <- <- IIb/IIIa inhibitors Jackson et al, NatRevDrugDiscov 2003

  5. Aspirin • Oraldrug • Irreversibly inactivates cyclooxygenase • Inhibits production of thromboxane A2 (TXA) • Limits TXA-mediated platelet activation and aggregation • Does not impact on other activation pathways and has highly variable response

  6. Clopidogrel • Oraldrug • Irreversiblyinactivates the P2Y12 plateletreceptorfor ADP • Limits P2Y12-mediated plateletactivation and aggregation • Does not impact on other activation pathways and has highly variable response

  7. State-of-the-artaspirin plus clopidogrel Rx Clopidogrel 600 mg loading, then 150 mg/dayfor 6 daysfollowedby 75 mg/day Clopidogrel 300 mg loading , then 75 mg/day CV death, MI, or stroke Mehtaet al, Lancet 2010

  8. Treatment alternatives Tanet al, CardiovascTher 2012

  9. Learninggoals • Scope of the problem • Prasugrel • Ticagrelor • Reconciling the evidence

  10. Prasugrel • Oraldrug • Irreversiblyinactivates the P2Y12 plateletreceptorfor ADP (more potently and predictablythan clopidogrel) • Limits P2Y12-mediated plateletactivation and aggregation • Does not impact on other activation pathways • 60 mg loading, 10 mg maintenance (5 mg if>75 years or <60 kg) • Aspirin dose isirrelevant

  11. Clopidogrel, prasugrel and ticagrelor Tanet al, CardiovascTher 2012

  12. Prasugrel hasanestablished and favorablerisk-benefitprofile Wiviottet al, New Engl J Med 2008

  13. Riskstratificationisofcourse key Montalescotet al, Lancet 2009

  14. Dose adjustmentispossible Erlingeet al, J Am CollCardiol 2012

  15. Loadingwithboth clopidogrel and prasugrel isnotprohibitive Lohet al, Am J Cardiol 2013

  16. Particularlyrisk-beneficial in diabetics Wiviottet al, Circulation 2008

  17. And even more so in IDDM Wiviottet al, Circulation 2008

  18. Lessclear-cut benefit in medicallymanaged ACS patients CV death, MI, or stroke HR=0.91 (0.79-1.05), p=0.21 Wiviottet al, Circulation 2008

  19. Last butnotleast • Are youafraidofincreasedneoplastic riskafterassuming prasugrel? • Do youknowhow long doesit take todevelopcancerafteryou are exposedto a nuclearbomb (e.g. Hiroshima)? • Anypurportedassociationbetween prasugrel and cancerrisk in TRITON-TIMI 38 patentlylacksbiologicplausibility

  20. Learninggoals • Scope of the problem • Prasugrel • Ticagrelor • Reconciling the evidence

  21. Ticagrelor • Oraldrug • Reversiblyantagonizes the P2Y12 plateletreceptorfor ADP • Thuslimits P2Y12-mediated plateletactivation and aggregation • Does not impact on other activation pathways • 180 mg load, 90 mg x 2/daymaintenance • Mustbeassociatedwith 75-100 mg/dayaspirin

  22. Clopidogrel, prasugrel and ticagrelor Tanet al, CardiovascTher 2012

  23. Steadilyincreasing benefit in all ACS Wallentinet al, New Engl J Med 2009

  24. Remarkablesafetyprofile vs clopidogrel Wallentinet al, New Engl J Med 2009

  25. Benefitsacross the board Wallentinet al, New Engl J Med 2009

  26. Non-CABGbleedingalso ↑ by ticagrelor Wallentinet al, New Engl J Med 2009

  27. Butthisis offset by ↓ CABG-relatedbleeds Cannonet al, Lancet 2010

  28. Are bradyarrhythmias major issues? Wallentinet al, New Engl J Med 2009

  29. Whataboutdyspnea and cancer? Wallentinet al, New Engl J Med 2009

  30. Whatabout creatinine and uric acid? Wallentinet al, New Engl J Med 2009

  31. Benefits are highlyconsistentbut… Cannonet al, Lancet 2010

  32. Learninggoals • Scope of the problem • Prasugrel • Ticagrelor • Reconciling the evidence

  33. First and foremost: both prasugrel and ticagrelor are lifesaving vs clopidogrel Biondi-Zoccaiet al, Int J Cardiol 2011

  34. Adjustedindirectcomparison Biondi-Zoccaiet al, Int J Cardiol 2011

  35. Adjustedindirectcomparison Biondi-Zoccaiet al, Int J Cardiol 2011

  36. Adjustedindirectcomparison Biondi-Zoccaiet al, Int J Cardiol 2011

  37. Do you trust plateletresponsivenessassays? Alexopouloset al, J Am CollCardiol 2012

  38. I personally don’t Biondi-Zoccaiet al, BMJ 2008 (butalsoGurbelet al, JAMA 2012; Colletet al, NEJM 2012; Gagliaet al, CardiovascRevascMed 2013; etc)

  39. Evenifyoubelieve… Alexopouloset al, CircCardiovascInterv 2012

  40. Reconciling the evidence Biondi-Zoccaiet al, CurrVascPharmacol 2012

  41. Take home messages • Both prasugrel and ticagrelor are superiorto clopidogrel in acute coronarysyndromes. • Prasugrel is best avoided in those at moderately high or high bleedingrisk (e.g. priorstroke/TIA) or whencoronaryinterventionisnotlikely. A 5 mg/day dose shouldbeused in the elderly or forweight <60 kg. • Ticagrelor is best avoided in those at high bleedingrisk, and mustbeassociatedwithlow-doseaspirin. • Awaiting the ACCOAST trial, ticagrelor appears more appealingthan prasugrel for NSTEACS ifantiplateletRxistobeinstituted in the ER, butequipoiseholdsfor STEMI.

  42. Manythanksforyourattention Fortheseslides and furtherones on similartopicsfeel free tovisit: www.metcardio.org/slides.html Foradditionaldetails or queriesfeel free tocontact me directly: giuseppe.biondizoccai@uniroma1.it

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