Switching antiplatelet regimens: alternatives to clopidogrel in STEMI patients

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1 Patras University Hospital Switching antiplatelet regimens: alternatives to clopidogrel in STEMI patients Dimitrios Alexopoulos, MD, FESC, FACC Professor of Cardiology Patras University Hospital Greece

2 Patras University Hospital I, Dimitrios Alexopoulos, have received honoraria for lecturing and research grants from: Astra Zeneca

3 Patras University Hospital Background Pharmacodynamic studies Randomised trials Guidelines Switching Registries

4 Activation of platelets in STEMI and mechanisms influencing adverse clinical outcomes Alexopoulos D, Intern J Cardiol 2011 Dec 20

5 A high platelet reactivity in STEMI patients Negatively impacts on the clopidogrel effect, Predicts PPCI success on angiography, degree of STsegment resolution, extent of myocardial necrosis, Predicts short- and mid-term clinical outcome Is associated with larger intracoronary thrombus and worse post-pci myocardial flow and perfusion. Gawaz M, et al.circulation 1996; 93: Campo G, et al. J Am Coll Cardiol 2006; 48: Matetzky S, et al Circulation 2004; 109: Vavuranakis M, et al. Circ J 2011; 75:

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8 Patras University Hospital Background Pharmacodynamic studies Randomised trials Guidelines Switching Registries

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10 Differences in metabolism among clopidogrel, prasugrel and ticagrelor explaining the variability of response to clopidogrel and the possible role of phenotyping and genotyping in STEMI patients. Alexopoulos D, Intern J Cardiol 2011 Dec 20

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12 Alexopoulos D, et al. Circ J 2012;76:2183

13 Funk-Jensen et al, Platelets 2012

14 50±36 minutes (median 44.5; interquartile range 35-60) Biscaglia S, et al JTH 2013 doi: /jth.12049

15 Biscaglia S, et al JTH 2013 doi: /jth.12049

16 Patras University Hospital Background Pharmacodynamic studies Randomised trials Guidelines Switching Registries

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23 Montalescot G et al Lancet 2009 Patras University Hospital

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27 Since the PLATO study design allowed for open-label clopidogrel to be administered before randomization, and 46% of the ticagrelor group received clopidogrel in this way, the PLATO trial was essentially a switch from clopidogrel to ticagrelor for these patients. The switch from clopidogrel to ticagrelor in the PLATO study did not result in any safety concerns.

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30 Patras University Hospital Background Pharmacodynamic studies Randomised trials Guidelines Switching Registries

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33 Patras University Hospital Background Pharmacodynamic studies Randomised trials Guidelines Switching Registries

34 Pharmacodynamic study of switching from clopidogrel to prasugrel/ticagrelor in healthy subjects, patients with ACS+PCI, diabetics, patients with HPR Switching from clopidogrel to prasugrel/ticagrelor Well tolerated. No major bleeding events by TIMI criteria. The clinical effect of switching on efficacy or safety in patients with ACS undergoing PCI has not been established- Nor in STEMI Angiolillo D et al JACC 2010;56:1017, Montalescot G et al Thromb Haemost 2010;103:213 Cuisset T et al Int J Card.2012 doi:pii: S , Alexopoulos D et al JACC Intv 2011;4:403 Gurbel P et al, Circulation, 2010;121:1188, Alexopoulos D et al JACC 2012;60:193

35 SWAP study Angiolillo D et al JACC 2010;56:1017

36 From: TCT-723 Transferring from Clopidogrel Loading Dose to Prasugrel Loading Dose in Acute Coronary Syndrome Patients: High on-treatment Platelet Reactivity Analysis of the TRIPLET Trial Date of download: 1/17/2013 Diodati J et al Copyright The American College of Cardiology. All rights reserved. J Am Coll Cardiol. 2012;60(17_S):. doi: /j.jacc

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40 Conclusions HTPR is commonly observed during the first 24 h post 600 mg clopidogrel LD in STEMI patients undergoing PPCI, at the time when platelet inhibition is mostly needed. In case of HTPR, prasugrel 60 mg LD administered on top and subsequent 10 mg MD provide faster and stronger platelet inhibition than a high clopidogrel MD regimen.

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44 Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST elevation myocardial infarction. D. Alexopoulos et al, Circ Interv 2012, DOI /CIRCINTERVENTIONS

45 Alexopoulos D, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST elevation myocardial infarction. Circ Cardiovasc Interv Patras University Hospital

46 TCT-744 Double (360mg) Loading Dose Of Ticagrelor In Patients With ST-elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Alexopoulos D., et al

47 Patras University Hospital Background Pharmacodynamic studies Randomised trials Guidelines Switching Registries

48 Switch and non switch in P2Y12 inhibition: the real life use of clopidogrel and prasugrel in patients with acute myocardial infarction. Insights from the FAST MI 2010 registry Schiele F et al ESC 2012 Nationwide French registry 4169 patients with AMI in 213 centres received thienopyridines, 1259 received prasugrel (31%). 391 received de novo prasugrel, 807 (64%) were treated with clopidogrel first and then switched to prasugrel 11% had a 60mg loading dose of prasugrel.

49 FAST MI 2010 registry A high proportion of patients treated with prasugrel were switched from clopidogrel therapy (64%). No evidence of excess risk of bleeding or inhospital complications in the patients who were switched, compared with those who received prasugrel treatment only.

50 GReek AntiPlatelet REgistry (GRAPE) 8 GREEK PCI HOSPITALS ΠΓΝ ΠΑΣΡΩΝ D. Alexopoulos, I. Xanthopoulou, K. Stavrou, E.Tsoni, A. Siapika, E.Mavronasiou, V. Gizas, A. Moulias, P. Davlouros, G. Hahalis ΠΕΠΑΓΝ ΗΡΑΚΛΕΙΟΤ M. Hamilos, Petousis, P.Vardas ΠΠΓΝ ΛΑΡΙΑ G. Sitafidis, G. Karayannis, H. Parissis, F.Triposkiadis ΠΠΓΝ ΙΩΑΝΝΙΝΩΝ I.Dallas, JA Goudevenos A ΠΑΝ/ΚΗ ΚΛΙN. ΙΠΠΟΚΡΑΣΕΙΟΤ M. Vavuranakis, C. Stefanadis ΓΝ ΚΡΑΣΙΚΟ ΑΘΗΝΩΝ S.Deftereos, C. Angelidis, G. Giannopoulos, V.Pyrgakis ΓΝ ΑΛΕΞΑΝΔΡΑ I. Kanakakis, S. Loizos ΠΠΓΝ ΑΛΕΞΑΝΔΡΟΤΠΟΛΗ D. Stakos, S. Konstantinides TARGET 1000 PATIENTS F-UP 1 YEAR. RECRUITED (15/1/2013) N=1411

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54 Switching according to primary PCI vs the rest ACS All others 376/ %

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58 TAKE HOME MESSAGES Switching from clopidogrel to prasugrel or ticagrelor may be an alternative for clinical settings (like STEMI) in which these drugs have shown to be more beneficial compared with clopidogrel. Switching from the novel P2Y12 receptor inhibitors to the less potent clopidogrel in patients with ACS should be considered for patients in whom the novel agents are contraindicated

59 When and whether to switch, and whether to administer an LD of prasugrel or ticagrelor at the time of switching, are clinical decisions left to the discretion of the treating clinician. Specifically designed studies evaluating the efficacy and safety related to switching from clopidogrel to either prasugrel or ticagrelor are not available.

60 Data from registries: Switching is the commonest practice. Age, PPCI, FMC at non- PCI hospital, prior clopidogrel, regional differences may influence upgrading