Indicazione, efficacia e sicurezza dello switching tra terapie antiaggreganti piastiniche

Indicazione, efficacia e sicurezza dello switching tra terapie antiaggreganti piastiniche Guido Parodi Dipartimento CardioToracoVascolare Azienda Ospedaliero-Universitaria Careggi Firenze CardioLucca Lucca, 28 Novembre 2014

SWITCHING OPTIONS DOWNGRADE CLOPIDOGREL UPGRADE PRASUGREL TICAGRELOR CHANGE

SWITCHING OPTIONS CLOPIDOGREL UPGRADE PRASUGREL TICAGRELOR

EYESHOT Registry Switching of P2Y12 inhibitor in patients with ACS: Insights from EYESHOT Registry (3 weeks: 2013-2014) N = 2585 ACS patients (1707 PCI) 242 (14.2%) SWITCHING N= 164 (68%) UPGRADE Clop Tica/Pras N= 55 (23%) DOWNGRADE Pras/Tica Clop N= 23 (9%) CHANGE Tica Pras Switching of P2Y12 inhibitor mostly represents upgrade from clopidogrel to ticagrelor or prasugrel but it is not frequent practice.

EYESHOT Registry P2Y12 Inhibitors at Discharge By Strategy NSTE-ACS N=1475 STEMI N=1034 28.2 41,5 1.0 68,4 35,9 34,6 36,4 0.6 9,1 % % n=242 n=384 n=811 n=38 n=39 n=81 n=903 n=11 No ADP Inhib (clopi/tica/prasu/ticlo)

PLATO study UA/NSTEMI (moderate-to-high risk) STEMI (if primary PCI) All receiving ASA; clopidogrel-treated (46%) or naive (54%); randomised within 24 hours of index event (N=18,624) Clopidogrel If pre-treated, no additional loading dose; if naive, standard 300 mg loading dose, then 75 mg qd maintenance; (additional 300 mg allowed pre PCI) Ticagrelor 180 mg loading dose, then 90 mg bid maintenance; (additional 90 mg pre-pci) Wallentin L et al. N Engl J Med. 2009;361:1045-57

PLATO study Wallentin L et al. N Engl J Med. 2009;361:1045-57

The RESPOND Study Inhibition of platelet aggregation in clopidogrel responders (n=57 stable CAD patients) Gurbel PA et al. Circulation 2010:121:1188-1199

Brar SS et al. J Am Coll Cardiol 2011;58:1945-54

cardiovascular death, nonfatal myocardial infarction, or stroke

P2Y 12 INHIBITORS 15%

The SWAP Study Switching AntiPlatelets (n=139 ACS patients) * p<0.0001 vs clopidogrel 75 mg MD p<0.0001 vs prasugrel 10 mg MD Angiolillo D et al. J Am Coll Cardiol 2010:56:1017

Previous clopidogrel load = 90 pts Prasugrel only load=516 pts Loh JP. Am J Cardiol 2013

Parodi G. J Thr Thombol 2014

Paper Patient population Pts switched to prasugrel 1. Payne CD, et al. Platelets. 2008;19(4):275-281. Healthy subjects 35 2. Wiviott SD, et al; PRINCIPLE-TIMI 44 trial. Circulation. 2007;116(25):2923-2932. CAD with planned PCI 55 3. Montalescot G et al. ACAPULCO study. Thromb Haemost. 2010;103(1):213-223. UA/NSTEMI ACS 49 4. Diodati JG, et al. TRIPLET trial. Circ Cardiovasc Interv. 2013 Oct 1;6(5):567-74. ACS anticipated to undergo PCI 167 5. Angiolillo DJ, et al; SWAP study. J Am Coll Cardiol. 2010;56(13):1017-1023 post-acs pts 91 6. Alexopoulos D, et al, Am Heart J. 2013 Jan;165(1):73-9. Elderly ACS PCI 27 7. Capranzano P, et al. Thromb Haemost 2011;106:1149-57. Elderly ACS PCI 20 8. Angiolillo DJ et al. OPTIMUS-3 Trial. Eur Heart J. 2011 ;32:838-46. type 2 DM and CAD 16 9. Cuisset T et al. Int J Cardiol 2013;168:523-8. diabetic PCI patients 107 10. Sardella G et al. RESET GENE trial. Circ Cardiovasc Interv. 2012 ;5:698-704. stable patients undergoing PCI 32 11. Alexopoulos D, et al. JACC Cardiovasc Interv. 2011;4:403-10. PCI w stent 68 12. Alexopoulos D, et al. J Thromb Haemost. 2011;9:2379-85. chronic HD with CAD 21 13. Alexopoulos D, et al. Am Heart J. 2011;162:733-9. Stable CAD, 87% undergoing PCI 30 9109 pts switched from clopidogrel to prasugrel 14. Loh JP et al. Am J Cardiol. 2013 Mar 15;111(6):841-5. ACS PCI 90 15. Lhermusier T, et al. J Thromb Haemost. 2012;10:1946-9. ACS PCI 80 16. Nührenberg TG, et al. Platelets. 2013;24:549-53. STEMI PCI 31 17. Aradi D, et al. J Am Coll Cardiol. 2014;63:1061-70. ACS PCI 91 18. Parodi G, et al. J Thromb Thrombolysis. 2014. [Epub ahead of print] STENTED PCI 315 19. De Luca G, et al. J Thromb Thrombolysis. 2014 [Epub ahead of print] ACS PCI 150 20. Alexopoulos D, et al. Am Heart J. 2014;167:68-76.e2. ACS PCI 255 21.Trenk D et al, TRIGGER-PCI (study. J Am Coll Cardiol 2012;59:2159-64. NSTE-ACS medically managed 212 22. Roe MT et al, TRILOGY ACS trial. N Engl J Med. 2012;367:1297-309. NSTE-ACS medically managed 3468 23. Bagai A et al, Circ Cardiovasc Interv. 2014;7:585-93. Acute MI and PCI 2125 24. SCAAR Registry. www.encepp.eu/encepp/openattachment/studyresultl_atest ACS PCI 1495 25. Clemmensen P et al., MULTIPRAC Registry. EHJ:ACC [Epub ahead of print] STEMI PCI 553

Pharmacodynamic Endpoints Primary Endpoint: PRU at 6 hrs 400 P=0.188 median 300 VN-P2Y12 PRU 200 100 0 placebo/ pras 60 mg clop 600 mg/ pras 60 mg clop 600 mg/ pras 30 mg n= 43 n= 38 n= 45 Diodati J and Angiolillo DJ. Circ Cardiovasc Interv 2013; 6(5):567-74

Prasugrel LD Alone vs. Clopidogrel + Prasugrel LDs PRASUGREL LD ALONE CLOPIDOGREL + PRASUGREL LDs PRASUGREL (AM) CLOPIDOGREL (AM) Platelet P2Y12 Receptor AM=Active Metabolite; LD=Loading Dose, PD=Pharmacodynamic Diodati J and Angiolillo DJ. Circ Cardiovasc Interv 2013; 6(5):567-74

2011

SWITCHING OPTIONS DOWNGRADE CLOPIDOGREL PRASUGREL TICAGRELOR

DOWNGRADING Background Prasugrel Clopidogrel 1)Increase of platelet aggregation (10-fold) 2) Unmask poor responder to clopidogrel 3) Reduce minor bleeding Kerneis M et al. JACC Cardiovac Interventions 2013

SWITCHING OPTIONS CLOPIDOGREL PRASUGREL TICAGRELOR CHANGE

SWAP 2 Ticagrelor Prasugrel PRU (mean ± SD) 350 300 250 200 150 100 Prasugrel 60 mg LD/ 10 mg MD Prasugrel 10 mg MD Prasugrel Total Ticagrelor 230 208 50 0 Pre-Run-In Baseline Pre- Rand. Baseline 2 hrs Post First Rand. Dose 4 hrs Post First Rand. Dose 24 hrs Post First Rand. Dose 48 hrs Post First Rand. Dose 7 Days Post First Rand. Dose Angiolillo D. J Am Coll Cardiol 2014

Sudden cardiac death of a patient with LM stent 48 hours after switching from Ticagrelor to Prasugrel without loading dose.

Parodi G and Storey RF. Eur Heart J: ACC 2014; Sep 29

Was identical characteristics, frequency and severity of DYSPNOEA episodes present before starting TICAGRELOR? NO YES Is the DYSPNOEA associated with orthopnoea, paroxysmal nocturnal dyspnoea or chest tightness or pain, related to exertion or limiting exercise capacity and/or is there an identifiable cause on physical examination? YES Look for an alternative cause NO Spontaneous DYSPNOEA improvement within 3 days Can the patient tolerate the DYSPNOEA with appropriate reassurance and counselling? NO NO Possible ticagrelorrelated DYSPNOEA Consider switching to prasugrel (or clopidogrel if prasugrel is contraindicated) using a full loading dose at least 24 hours from the last ticagrelor intake YES YES FOLLOW-UP Parodi G and Storey RF. Eur Heart J: ACC 2014; Sep 29

CONCLUSIONS 1) Switching from Clopidogrel to Ticagrelor or Prasugrel reduces platelet reactivity 3) Whether to switch depend on risk profile (anatomy) 4) How to switch: starting with a loading dose 5) Downgrading to clopidogrel should be considered only in the case of relevant sideeffect or of the need for oral anticoagulation 6) A warning regarding switching from ticagrelor to prasugrel (or clopidogrel)!

MOST FREQUENT SWITCH