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Patras University Hospital

Switching antiplatelet regimens: alternatives to clopidogrel in

STEMI patients

Dimitrios Alexopoulos, MD, FESC, FACC

Professor of Cardiology


Greece


I, Dimitrios Alexopoulos, have received

honoraria for lecturing

and research grants from:

Astra Zeneca


Background

Pharmacodynamic studies

Randomised trials

Guidelines

Switching

Registries

Activation of platelets in STEMI and mechanisms

influencing adverse clinical outcomes

Alexopoulos D, Intern J Cardiol 2011 Dec 20

A high platelet reactivity in STEMI patients

•Negatively impacts on the clopidogrel effect,

•Predicts PPCI success on angiography, degree of ST-

segment 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: 229 – 237.

Campo G, et al. J Am Coll Cardiol 2006; 48: 2178 – 2185.

Matetzky S, et al Circulation 2004; 109: 3171 – 3175.

Vavuranakis M, et al. Circ J 2011; 75: 2105 – 2112.



Background


Randomised trials

Guidelines

Switching

Registries

Thromb Res 2008

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


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

Funk-Jensen et al, Platelets 2012

Biscaglia S, et al JTH 2013 doi: 10.1111/jth.12049

50±36 minutes (median 44.5; interquartile range 35-

60)

Biscaglia S, et al JTH 2013 doi: 10.1111/jth.12049


Background


Randomised trials

Guidelines

Switching

Registries







Patras University HospitalMontalescot G et al Lancet 2009



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.



Background


Randomised trials

Guidelines

Switching

Registries




Background


Randomised trials

Guidelines

Switching

Registries

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: S0167-5273, 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

Angiolillo D et al JACC 2010;56:1017

SWAP study

Date of download:

1/17/2013

Copyright © The American College of Cardiology.

All rights reserved.

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

J Am Coll Cardiol. 2012;60(17_S):. doi:10.1016/j.jacc.2012.08.764Diodati J et al


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.




Randomized assessment of ticagrelor versus prasugrel antiplateleteffects in patients with ST elevation myocardial infarction.

D. Alexopoulos et al, Circ Interv 2012, DOI 10.1161/CIRCINTERVENTIONS.112.972323


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

TCT-744

Double (360mg) Loading Dose Of Ticagrelor In Patients With ST-elevation

Myocardial Infarction Undergoing Primary Percutaneous Coronary

Intervention

Alexopoulos D., et al


Background


Randomised trials

Guidelines

Switching

Registries

Nationwide French registry 4169 patients with AMI in 213 centres.

4115 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.

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

A high proportion of patients treated with

prasugrel were switched from clopidogrel therapy

(64%).

No evidence of excess risk of bleeding or in-

hospital complications in the patients who were

switched, compared with those who received

prasugrel treatment only.

FAST MI 2010 registry

GReek AntiPlatelet REgistry (GRAPE)

8 GREEK PCI HOSPITALSΠΓΝ 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

681 patients with STEMI

Switching according to primary PCI vs the rest ACS

All others 376/866 43.4%

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

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.

Data from registries:

Switching is the commonest practice.

Age, PPCI, FMC at non- PCI hospital, prior

clopidogrel, regional differences may influence

upgrading

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Switching antiplatelet regimens: alternatives to ...static.livemedia.gr/livemedia/documents/Alpic190113_008_alexopoul… · Differences in metabolism among clopidogrel, prasugrel