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Patras University Hospital
Switching antiplatelet regimens: alternatives to clopidogrel in
STEMI patients
Dimitrios Alexopoulos, MD, FESC, FACC
Professor of Cardiology
Patras University Hospital
Greece
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Patras University Hospital
I, Dimitrios Alexopoulos, have received
honoraria for lecturing
and research grants from:
Astra Zeneca
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Patras University Hospital
Background
Pharmacodynamic studies
Randomised trials
Guidelines
Switching
Registries
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Activation of platelets in STEMI and mechanisms
influencing adverse clinical outcomes
Alexopoulos D, Intern J Cardiol 2011 Dec 20
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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.
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Patras University Hospital
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Patras University Hospital
Background
Pharmacodynamic studies
Randomised trials
Guidelines
Switching
Registries
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Thromb Res 2008
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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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Patras University Hospital
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Alexopoulos D, et al. Circ J 2012;76:2183
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Funk-Jensen et al, Platelets 2012
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Biscaglia S, et al JTH 2013 doi: 10.1111/jth.12049
50±36 minutes (median 44.5; interquartile range 35-
60)
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Biscaglia S, et al JTH 2013 doi: 10.1111/jth.12049
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Patras University Hospital
Background
Pharmacodynamic studies
Randomised trials
Guidelines
Switching
Registries
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Patras University Hospital
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Patras University Hospital
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Patras University Hospital
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Patras University Hospital
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Patras University Hospital
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Patras University Hospital
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Patras University HospitalMontalescot G et al Lancet 2009
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Patras University Hospital
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Patras University Hospital
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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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Patras University Hospital
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Patras University Hospital
Background
Pharmacodynamic studies
Randomised trials
Guidelines
Switching
Registries
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Patras University Hospital
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Patras University Hospital
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Patras University Hospital
Background
Pharmacodynamic studies
Randomised trials
Guidelines
Switching
Registries
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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
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Angiolillo D et al JACC 2010;56:1017
SWAP study
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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
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Patras University Hospital
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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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Patras University Hospital
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Patras University Hospital
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Patras University Hospital
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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
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Patras University Hospital
Alexopoulos D, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST elevation myocardial infarction. Circ Cardiovasc Interv. 2012
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TCT-744
Double (360mg) Loading Dose Of Ticagrelor In Patients With ST-elevation
Myocardial Infarction Undergoing Primary Percutaneous Coronary
Intervention
Alexopoulos D., et al
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Patras University Hospital
Background
Pharmacodynamic studies
Randomised trials
Guidelines
Switching
Registries
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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
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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
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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
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681 patients with STEMI
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Switching according to primary PCI vs the rest ACS
All others 376/866 43.4%
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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
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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.
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Data from registries:
Switching is the commonest practice.
Age, PPCI, FMC at non- PCI hospital, prior
clopidogrel, regional differences may influence
upgrading