Thromb Haemost 2014; 112(02): 342-351
DOI: 10.1160/TH13-10-0874
Platelets and Blood Cells
Schattauer GmbH

A comparative cohort study on personalised antiplatelet therapy in PCI-treated patients with high on-clopidogrel platelet reactivity

Results of the ISAR-HPR registry
Katharina Mayer
1   Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
,
Stefanie Schulz
1   Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
,
Isabell Bernlochner
2   I. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
,
Tanja Morath
1   Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
,
Siegmund Braun
1   Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
,
Jörg Hausleiter
3   Department of Cardiology, Ludwig-Maximilians-Universität, Munich, Germany
,
Steffen Massberg
3   Department of Cardiology, Ludwig-Maximilians-Universität, Munich, Germany
,
Heribert Schunkert
1   Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
4   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Karl-Ludwig Laugwitz
2   I. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
4   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Adnan Kastrati
1   Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
4   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Dirk Sibbing
3   Department of Cardiology, Ludwig-Maximilians-Universität, Munich, Germany
4   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
› Institutsangaben
Financial support: Funding was provided by the Munich Heart Alliance, Munich, Germany.
Weitere Informationen

Publikationsverlauf

Received: 27. Oktober 2013

Accepted after major revision: 04. März 2014

Publikationsdatum:
04. Dezember 2017 (online)

Summary

In clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI), high platelet reactivity (HPR) is associated with a higher risk for thrombotic events including stent thrombosis (ST). A personalised therapy with selective intensification of treatment may improve HPR patients´ outcome in this setting although recent randomised trials are against this hypothesis. The aim of the ISAR-HPR registry was to assess whether clopidogrel-treated HPR patients benefit from selective intensification of P2Y12 receptor inhibition. For the registry, outcomes were compared between two cohorts. We identified 428 clopidogrel treated HPR patients (AU x min ≥468 on the Multiplate analyser) between 2007–2008 (historical control cohort) without a change of treatment based on platelet function (PF) testing results. Between 2009–2011, we identified 571 HPR patients (guided therapy cohort) and used this information for guidance and selective intensification of P2Y12 receptor directed treatment (reloading with clopidogrel, switch to prasugrel, re-testing) in a setting of routine PF testing. The primary outcome was the composite of death from any cause or ST after 30 days. Major bleeding according to TIMI criteria was also monitored. The incidence of the primary outcome was significantly lower in the guided vs the control cohort (7 [1.2%] vs 16 [3.7%] events; HR 0.32, 95% CI 0.13–0.79; p=0.009). The incidence of major bleeding was numerically but not statistically higher in the guided vs the control cohort (1.9 vs 0.7%; p=0.10). In conclusion, present findings are in support for a PF testing guided antiplatelet therapy with selective intensification of P2Y12 receptor inhibition. The issue of personalised antiplatelet treatment warrants further investigation in randomized and well-controlled clinical trials.

 
  • References

  • 1 Hamm CW, Bassand JP, Agewall S. et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 2999-3054.
  • 2 Neubauer H, Meves SH. Bedside monitoring of antiplatelet therapy for coronary stenting. N Engl J Med 2013; 368: 870-871.
  • 3 Mahla E, Antonino MJ, Tantry US. et al. Point-of-care platelet function analysis ready for prime time?. J Am Coll Cardiol 2009; 53: 857-859.
  • 4 Aradi D, Komocsi A, Price MJ. et al. Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention: Systematic review and meta-analysis. Int J Cardiol 2013; 167: 2140-2148.
  • 5 Trenk D, Stone GW, Gawaz M. et al. A Randomised Trial of Prasugrel Versus Clopidogrel in Patients With High Platelet Reactivity on Clopidogrel After Elective Percutaneous Coronary Intervention With Implantation of Drug-Eluting Stents: Results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) Study. J Am Coll Cardiol 2012; 59: 2159-2164.
  • 6 Price MJ, Berger PB, Teirstein PS. et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomised trial. J Am Med Assoc 2011; 305: 1097-1105.
  • 7 Collet JP, Cuisset T, Range G. et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100-2109.
  • 8 Stone GW. ADAPT-DES: A Large-Scale, Prospective, Multicenter Registry Examining the Relationship of Platelet Responsiveness to Stent Thrombosis After DES Implantation. Transcatheter Cardiovascular Therapeutics. 2011. San Francisco: November 9, 2011
  • 9 Siller-Matula JM, Francesconi M, Dechant C. et al. Personalised antiplatelet treatment after percutaneous coronary intervention: The MADONNA study. Int J Cardiol 2013; 167: 2018-2023.
  • 10 Bonello L, Camoin-Jau L, Arques S. et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomised prospective study. J Am Coll Cardiol 2008; 51: 1404-1411.
  • 11 Sibbing D, Steinhubl SR, Schulz S. et al. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 2010; 56: 317-318.
  • 12 Bonello L, Tantry US, Marcucci R. et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-933.
  • 13 Sibbing D, Braun S, Morath T. et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009; 53: 849-856.
  • 14 Cutlip DE, Windecker S, Mehran R. et al. Clinical end points in coronary stent trials: a case for standardised definitions. Circulation 2007; 115: 2344-2351.
  • 15 Siller-Matula JM, Haberl K, Prillinger K. et al. The effect of antiplatelet drugs clopidogrel and aspirin is less immediately after stent implantation. Thromb Res 2009; 123: 874-880.
  • 16 Wiviott SD, Braunwald E, McCabe CH. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
  • 17 Wallentin L, Becker RC, Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
  • 18 Jaitner J, Stegherr J, Morath T. et al. Stability of the high on-treatment platelet reactivity phenotype over time in clopidogrel-treated patients. Thromb Haemost 2011; 105: 107-112.
  • 19 Siller-Matula JM, Jilma B. Why have studies of tailored anti-platelet therapy failed so far?. Thromb Haemost 2013; v110: 628-631.
  • 20 Hochholzer W, Trenk D, Bestehorn HP. et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol 2006; 48: 1742-1750.
  • 21 Aradi D, Kuliczkowski W, Atar D. et al. Inter-patient variability and impact of proton pump inhibitors on platelet reactivity after prasugrel. Thromb Haemost 2012; 107: 338-345.
  • 22 Alexopoulos D, Plakomyti TE, Xanthopoulou I. Variability and treatment of high on-prasugrel platelet reactivity in patients with initial high on-clopidogrel platelet reactivity. Int J Cardiol 2012; 154: 333-334.
  • 23 Bonello L, Pansieri M, Mancini J. et al. High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes. J Am Coll Cardiol 2011; 58: 467-473.
  • 24 Task Force on the management of STEMI. Steg PG, James SK. et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-2619.
  • 25 Serebruany V, Atar D. Prasugrel: the real-life perspective. Circ Cardiovasc Qual Outcomes 2013; 06: 253-254.
  • 26 Tantry US, Bonello L, Aradi D. et al. Consensus and Update on the Definition of On-Treatment Platelet Reactivity to ADP Associated with Ischaemia and Bleeding. J Am Coll Cardiol 2013; 62: 2261-2273.
  • 27 Aradi D, Tornyos A, Pintér T. et al. Optimizing P2Y12-receptor inhibition in acute coronary syndrome patients based on platelet function testing: impact of prasugrel and high-dose clopidogrel. J Am Coll Cardiol 2014; 1061-1070.