“Indicazione, efficacia e sicurezzadello switching tra terapie antiaggreganti piastiniche”

Guido ParodiDipartimento CardioToracoVascolare

Azienda Ospedaliero-Universitaria CareggiFirenze

CardioLuccaLucca, 28 Novembre 2014

CLOPIDOGREL

PRASUGREL TICAGRELOR

UPGRADEDOWNGRADE

CHANGE

SWITCHING OPTIONS

CLOPIDOGREL

PRASUGREL TICAGRELOR

UPGRADE

SWITCHING OPTIONS

Switching of P2Y12 inhibitor in patients with ACS:Insights from EYESHOT Registry (3 weeks: 2013-2014)

N = 2585 ACS patients (1707 PCI)

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.

242 (14.2%) SWITCHING

EYESHOT

Registry

%

NSTE-ACS

N=1475

P2Y12 Inhibitors at DischargeBy Strategy

%

STEMI

N=1034

9,1

n=39 n=81 n=903 n=11n=242 n=384 n=811 n=38

No ADP Inhib (clopi/tica/prasu/ticlo)

28.2 41,568,4

1.035,9 34,6 36,40.6

EYESHOT

Registry

PLATO study

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)

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)

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

Gurbel PA et al. Circulation 2010:121:1188-1199

The RESPOND StudyInhibition of platelet aggregation in clopidogrel responders

(n=57 stable CAD patients)

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

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15%

P2Y12 INHIBITORS

Angiolillo D et al. J Am Coll Cardiol 2010:56:1017

The SWAP StudySwitching AntiPlatelets (n=139 ACS patients)

* p<0.0001 vs clopidogrel 75 mg MD

† p<0.0001 vs prasugrel 10 mg MD

Loh JP. Am J Cardiol 2013

Previous clopidogrel load = 90 pts

Prasugrel only load=516 pts

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

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

9109 pts switched

from clopidogrel to

prasugrel

VN

-P2

Y12 P

RU

0

100

200

300

400

clop 600 mg/pras 60 mg

clop 600 mg/pras 30 mg

median

placebo/pras 60 mg

Pharmacodynamic

Endpoints

Primary Endpoint:

PRU at 6 hrs

n= 43 n= 38 n= 45

P=0.188

Diodati J and Angiolillo DJ. Circ Cardiovasc Interv 2013; 6(5):567-74

Prasugrel LD Alone vs. Clopidogrel + Prasugrel LDs

PRASUGREL (AM) CLOPIDOGREL (AM)

PRASUGREL LD ALONE CLOPIDOGREL + PRASUGREL LDs

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

CLOPIDOGREL

PRASUGREL TICAGRELOR

DOWNGRADE

SWITCHING OPTIONS

BackgroundBackground

Kerneis M et al. JACC Cardiovac Interventions 2013

1) Increase of platelet aggregation (10-fold)

2) Unmask poor responder to clopidogrel

3) Reduce minor bleeding

DOWNGRADINGPrasugrel → Clopidogrel

CLOPIDOGREL

PRASUGREL TICAGRELOR

CHANGE

SWITCHING OPTIONS

0

50

100

150

200

250

300

350

Prasugrel 60 mg LD/

10 mg MDPrasugrel 10 mg MD

Prasugrel Total

Ticagrelor

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

230208

PR

U (

me

an

±S

D)

SWAP 2Ticagrelor → Prasugrel

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?

Spontaneous DYSPNOEA

improvement within 3 days

YES

FOLLOW-UP

NO

Can the patient tolerate the DYSPNOEA

with appropriate reassurance and counselling?

YESNO

Consider switching to prasugrel (or clopidogrel if

prasugrel is contraindicated) using a full loading dose at least 24 hours from the last ticagrelor intake

Look for an alternative

cause

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?

NO

YES Possible ticagrelor-

related DYSPNOEA

NO

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 side-

effect or of the need for oral anticoagulation

6) A warning regarding switching from ticagrelor to

prasugrel (or clopidogrel)!

MOST FREQUENT SWITCH