384
Views
6
CrossRef citations to date
0
Altmetric
Special Review: Platelets at the Heart of Therapy

Personalizing antiplatelet therapies: What have we learned from recent trials?

, & ORCID Icon
Pages 131-139 | Received 05 Apr 2017, Accepted 10 Apr 2017, Published online: 19 Jun 2017

References

  • Schulz C, Massberg S. Platelets in atherosclerosis and thrombosis. Handb Exp Pharmacol 2012;210:111–133.
  • Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American college of cardiology foundation/American heart association task force on practice guidelines and the society for cardiovascular angiography and interventions. Circulation 2011;124(23):e574–651.
  • Bittl JA, Baber U, Bradley SM, Wijeysundera DN. Duration of dual antiplatelet therapy: A systematic review for the 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation 2016;134:e156–178.
  • Kushner FG, Hand M, Smith SC, King SB, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DE, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (Updating the 2005 guideline and 2007 focused update). J Am Coll Cardiol 2009;54:2205–2241.
  • Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Clopidogrel in unstable angina to prevent recurrent events trial investigators: effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502.
  • Moussa I, Oetgen M, Roubin G, Colombo A, Wang X, Iyer S, Maida R, Collins M, Kreps E, Moses JW. Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation. Circulation 1999;99:2364–2366.
  • Steinhubl SR, Berger PB, Mann JT III, Fry ETA, DeLago A, Wilmer C, Topol EJ. Investigators FTC: early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: A randomized controlled trial. JAMA 2002;288:2411–2420.
  • Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372:1791–1800.
  • Halkar M, Lincoff AM. Dual antiplatelet therapy for acute coronary syndromes: How long to continue? Cleve Clin J Med 2016;83:675–688.
  • Sabouret P, Rushton-Smith SK, Kerneis M, Silvain J, Collet J-P, Montalescot G. Dual antiplatelet therapy: Optimal timing, management, and duration. Eur Heart J Cardiovasc Pharmacother 2015;1:198–204.
  • Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A Report of the American college of cardiology/American heart association task force on clinical practice guidelines. J Am Coll Cardiol 2016;68:1082–1115.
  • Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: The PCI-CURE study. The Lancet 2001;358:527–533.
  • Tantry US, Gesheff M, Liu F, Bliden KP, Gurbel PA. Resistance to antiplatelet drugs: What progress has been made? Expert Opin Pharmacother 2014;15:2553–2564.
  • Kovács EG, Katona É, Bereczky Z, Homoródi N, Balogh L, Tóth E, Péterfy H, Kiss RG, Édes I, Muszbek L. New direct and indirect methods for the detection of cyclooxygenase 1 acetylation by aspirin; the lack of aspirin resistance among healthy individuals. Thromb Res 2013;131:320–324.
  • Tran HA, Anand SS, Hankey GJ, Eikelboom JW. Aspirin resistance. Thromb Res 2007;120:337–346.
  • Lordkipanidzé M. Advances in monitoring of aspirin therapy. Platelets 2012;23:526–536.
  • Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann F-J, Metzger DC, Henry TD, Cox DA, Duffy PL, Mazzaferri E, et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): A prospective multicentre registry study. Lancet 2013;382:614–623.
  • Mayer K, Bernlochner I, Braun S, Schulz S, Orban M, Morath T, Cala L, Hoppmann P, Schunkert H, Laugwitz K-L, et al. Aspirin treatment and outcomes after percutaneous coronary intervention: Results of the ISAR-ASPI registry. J Am Coll Cardiol 2014;64:863–871.
  • Price MJ, Berger PB, Teirstein PS, Tanguay J-F, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011;305:1097–1105.
  • Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: A review of the evidence. J Am Coll Cardiol 2005;45:1157–1164.
  • Brar SS, Berg Ten J, Marcucci R, Price MJ, Valgimigli M, Kim HS, Patti G, Breet NJ, DiSciascio G, Cuisset T, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. J Am Coll Cardiol 2011;58:1945–1954.
  • Matetzky S. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004;109:3171–3175.
  • Tantry US, Bonello L, Aradi D, Price MJ, Jeong Y-H, Angiolillo DJ, Stone GW, Curzen N, Geisler T, Berg Ten J, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013;62(24):2261–2273.
  • Marcucci R, Gori AM, Paniccia R, Giusti B, Valente S, Giglioli C, Buonamici P, Antoniucci D, Abbate R, Gensini GF. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: A 12-month follow-up. Circulation 2009;119:237–242.
  • Aradi D, Kirtane A, Bonello L, Gurbel PA, Tantry US, Huber K, Freynhofer MK, Berg Ten J, Janssen P, Angiolillo DJ, et al. Bleeding and stent thrombosis on P2Y 12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015;36:1762–1771.
  • Sibbing D, Steinhubl SR, Schulz S, Schömig A, Kastrati A. 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.
  • Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, 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.
  • Lordkipanidzé M. Platelet function tests. Semin Thromb Hemost 2016;42:258–267.
  • Bouman HJ, Parlak E, van Werkum JW, Breet NJ, Cate TH, Hackeng CM, Berg Ten JM, Taubert D. Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel. J Thromb Haemost 2010;8:482–488.
  • Koziński M, Ostrowska M, Adamski P, Sikora J, Sikora A, Karczmarska-Wódzka A, Marszałł MP, Boinska J, Laskowska E, Obońska E, et al. Which platelet function test best reflects the in vivo plasma concentrations of ticagrelor and its active metabolite? Thromb Haemost 2016;116:1140–1149.
  • Le Quellec S, Bordet JC, Negrier C, Dargaud Y. Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response. Thromb Haemost 2016;116:638–650.
  • Lordkipanidze M, Pharand C, Nguyen TA, Schampaert E, Palisaitis DA, Diodati JG. Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients. Eur Heart J 2008;29:2877–2885.
  • Kirtane AJ, Parikh PB, Stuckey TD, Xu K, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann F-J, Metzger DC, Henry TD, et al. Is there an ideal level of platelet P2Y12-receptor inhibition in patients undergoing percutaneous coronary intervention? “Window” analysis from the ADAPT-DES Study (Assessment of dual antiplatelet therapy with drug-eluting stents). JACC: Cardiovasc Interventions 2015;8:1978–1987.
  • Dahlen JR, Price MJ, Parise H, Gurbel PA. Evaluating the clinical usefulness of platelet function testing: considerations for the proper application and interpretation of performance measures. Thromb Haemost 2013;109:808–816.
  • Saw J, Madsen EH, Chan S, Maurer-Spurej E. The ELAPSE (Evaluation of long-term clopidogrel antiplatelet and systemic anti-inflammatory effects) study. J Am Coll Cardiol 2008;52:1826–1833.
  • Jaitner J, Stegherr J, Morath T, Braun S, Bernlochner I, Schömig A, Kastrati A, Sibbing D. Stability of the high on-treatment platelet reactivity phenotype over time in clopidogrel-treated patients. Thromb Haemost 2011;105:107–112.
  • Nührenberg TG, Stratz C, Leggewie S, Hochholzer W, Valina CM, Gick M, Kirtane AJ, Stone GW, Neumann F-J, Trenk D. Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation. An ADAPT-DES substudy</b>. Thromb Haemost 2015;114:1020–1027.
  • Hochholzer W, Ruff CT, Mesa RA, Mattimore JF, Cyr JF, Lei L, Frelinger AL, Michelson AD, Berg DD, Angiolillo DJ, et al. Variability of individual platelet reactivity over time in patients treated with clopidogrel: Insights from the ELEVATE-TIMI 56 trial. J Am Coll Cardiol 2014;64:361–368.
  • Trenk D, Stone GW, Gawaz M, Kastrati A, Angiolillo DJ, Müller U, Richardt G, Jakubowski JA, Neumann FJ. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents. J Am Coll Cardiol 2012;59:2159–2164.
  • Price MJ, Endemann S, Gollapudi RR, Valencia R, Stinis CT, Levisay JP, Ernst A, Sawhney NS, Schatz RA, Teirstein PS. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 2008;29:992–1000.
  • Sibbing D, Schulz S, Braun S, Morath T, Stegherr J, Mehilli J, Schömig A, Beckerath Von N, Kastrati A. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost 2010;8:250–256.
  • Patti G, Pasceri V, Vizzi V, Ricottini E, Di Sciascio G. Usefulness of platelet response to clopidogrel by point-of-care testing to predict bleeding outcomes in patients undergoing percutaneous coronary intervention (from the antiplatelet therapy for reduction of myocardial damage during angioplasty-bleeding study). Am J Cardiol 2011;107:995–1000.
  • Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: A time-dependent analysis of the gauging responsiveness with a verifynow P2Y12 assay: Impact on thrombosis and safety (GRAVITAS) trial. Circulation 2011;124:1132–1137.
  • Collet J-P, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C, Henry P, Motreff P, Carrié D, Boueri Z, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012;367:2100–2109.
  • Collet J-P, Cayla G, Cuisset T, Elhadad S, Rangé G, Vicaut E, Montalescot G. Randomized comparison of platelet function monitoring to adjust antiplatelet therapy versus standard of care: Rationale and design of the assessment with a double randomization of (1) a fixed dose versus a monitoring-guided dose of aspirin and clopidogrel after DES implantation, and (2) treatment interruption versus continuation, 1 year after stenting (ARCTIC) study. Am Heart J 2011;161:5–12.e5.
  • Siller-Matula JM, Francesconi M, Dechant C, Jilma B, Maurer G, Delle-Karth G, Gouya G, Ruzicka K, Podczeck-Schweighofer A, Christ G. Personalized antiplatelet treatment after percutaneous coronary intervention: The MADONNA study. Int J Cardiol 2013;167:2018–2023.
  • Mayer K, Schulz S, Bernlochner I, Morath T, Braun S, Hausleiter J, Massberg S, Schunkert H, Laugwitz KL, Kastrati A, et al. A comparative cohort study on personalised antiplatelet therapy in PCI-treated patients with high on-clopidogrel platelet reactivity. Results of the ISAR-HPR registry. Thromb Haemost 2014;112:342–351.
  • Aradi D, Tornyos A, Pintér T, Vorobcsuk A, Kónyi A, Faluközy J, Veress G, Magyari B, Horváth IG, Komócsi A. Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: Impact of prasugrel and high-dose clopidogrel. J Am Coll Cardiol 2014;63:1061–1070.
  • Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C, Delarche N, Bellemain-Appaix A, Rangé G, Mahmoud El R, et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): An open-label, blinded-endpoint, randomised controlled superiority trial. Lancet 2016;388:2015–2022.
  • Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann F-J, Ardissino D, De Servi S, Murphy SA, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–2015.
  • Erlinge D, Berg Ten J, Foley D, Angiolillo DJ, Wagner H, Brown PB, Zhou C, Luo J, Jakubowski JA, Moser B, et al. Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients. Jac 2012;60:2032–2040.
  • Erlinge D, Gurbel PA, James S, Lindahl TL, Svensson P, Berg Ten JM, Foley DP, Wagner H, Brown PB, Luo J, et al. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: The GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol 2013;62:577–583.
  • Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, Huber K, EPA (European Platelet Academy).Response variability to P2Y12 receptor inhibitors: Expectations and reality. JACC: Cardiovasc Interventions 2013;6:1111–1128.
  • Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, Ferrières J, Danchin N, Becquemont L, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363–375.
  • Collet J-P, Hulot J-S, Pena A, Villard E, Esteve J-B, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: A cohort study. The Lancet 2009;373:309–317.
  • Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354–362.
  • Mega JL, Hochholzer W, Frelinger AL, Kluk MJ, Angiolillo DJ, Kereiakes DJ, Isserman S, Rogers WJ, Ruff CT, Contant C, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA 2011;306:1–8.
  • Doll JA, Neely ML, Roe MT, Armstrong PW, White HD, Prabhakaran D, Winters KJ, Duvvuru S, Sundseth SS, Jakubowski JA, et al. Impact of CYP2C19 metabolizer status on patients with ACS treated with prasugrel versus clopidogrel. J Am Coll Cardiol 2016;67:936–947.
  • Roberts JD, Wells GA, Le May MR, Labinaz M, Glover C, Froeschl M, Dick A, Marquis J-F, O’Brien E, Goncalves S, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): A prospective, randomised, proof-of-concept trial. The Lancet 2012;379:1705–1711.
  • Kołtowski Ł, Aradi D, Huczek Z, Tomaniak M, Sibbing D, Filipiak KJ, Kochman J, Balsam P, Opolski G. Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): A prospective, open-label, randomised parallel-group multicentre trial (NCT01930773). Kardiol Pol 2016;74:372–379.
  • Fuster V, Bhatt DL, Califf RM, Michelson AD, Sabatine MS, Angiolillo DJ, Bates ER, Cohen DJ, Coller BS, Furie B, et al. Guided antithrombotic therapy: Current status and future research direction: report on a National Heart, Lung and Blood Institute working group. Circulation 2012;126(13):1645–1662.
  • Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–1057.
  • Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM, investigators FTT-T3. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): Double-blind, randomised controlled trial. The Lancet 2009;373:723–731.
  • Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Gori T, Hadamitzky M, Merkely B, et al. A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Thromb Haemost 2017;117:188–195.
  • Jiang M, You JH. Cost-effectiveness analysis of personalized antiplatelet therapy in patients with acute coronary syndrome. Pharmacogenomics 2016;17:701–713.
  • De Witt SM, Swieringa F, Cavill R, Lamers MME, Van Kruchten R, Mastenbroek T, Baaten C, Coort S, Pugh N, Schulz A, et al. Identification of platelet function defects by multi-parameter assessment of thrombus formation. Nat Commun 2014;5:1–13.
  • Lordkipanidzé M, Lowe GC, Kirkby NS, Chan MV, Lundberg MH, Morgan NV, Bem D, Nisar SP, Leo VC, Jones ML, et al. Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: Use of 96-well Optimul assay. Blood 2014;123:e11–22.
  • Bergmeijer TO, Janssen PWA, Schipper JC, Qaderdan K, Ishak M, Ruitenbeek RS, Asselbergs FW, Van ‘T Hof AWJ, Dewilde WJM, Spanó F, et al. CYP2C19 genotype-guided antiplatelet therapy in ST-segment elevation myocardial infarction patients - Rationale and design of the Patient Outcome after primary PCI (POPular) Genetics study. Am Heart J 2014;168:16–22.e1.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.