Vol 25, No 1 (2018)
Review articles — Clinical cardiology
Published online: 2017-10-18

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Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

Yong Zhang123, Pei Zhang12, Zhan Li12, Juanjuan Du12, Jiangrong Wang1, Xiuqing Tian1, Mei Gao2, Yinglong Hou1
Pubmed: 29064534
Cardiol J 2018;25(1):128-141.

Abstract

 Background: The preventive effects of laboratory personalized antiplatelet therapy (PAPT) strategy in­cluding genetic detection and platelet function testing (PFT) on major adverse cardiac events (MACEs) and bleeding events in coronary artery disease (CAD) patients undergoing stenting has been extensively studied. Despite that, no clear conclusion can be drawn. In this study, a meta-analysis was performed to explore a more precise estimation of the benefits of laboratory PAPT.

Methods: Randomized controlled trials were identified by the use of search databases such as PubMed, Embase, and Cochrane Controlled Trials Register up to May 2017, and the estimates were pooled.

Results: Fourteen studies including 9497 patients met the inclusion criteria. The laboratory PAPT reduced MACEs risk (risk ratio [RR] 0.58, 95% confidence interval [CI] 0.42–0.80, p = 0.001), stent thrombosis (RR 0.60, 95% CI 0.41–0.87, p = 0.008) and myocardial infarctions (RR 0.43, 95% CI 0.21–0.88, p = 0.02) compared to the non-PAPT group. No statistically significant difference was observed between the two groups regarding cardiovascular death (RR 0.77, 95% CI 0.51–1.16, p = 0.21), bleeding events (RR 0.96, 95% CI 0.81–1.13, p = 0.59) and ischemic stroke (RR 0.81; 95% CI 0.39–1.66, p = 0.57). The preventive effect on MACEs was more significant in patients with high on-treatment platelet reactivity (RR 0.46; 95% CI 0.27–0.80, p = 0.006).

Conclusions: Coronary artery disease patients after stenting could obtain benefits from laboratory PAPT. (Cardiol J 2018; 25, 1: 128–141)

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References

  1. Levine GN, Bates ER, Bittl JA, 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: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016; 134(10): e123–e155.
  2. Kolh P, Windecker S, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg. 2014; 46(4): 517–592.
  3. Gurbel PA, Bliden KP, Hiatt BL, et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003; 107(23): 2908–2913.
  4. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004; 109(25): 3171–3175.
  5. Tantry US, Bonello L, Aradi D, et al. Working Group on On-Treatment Platelet Reactivity. 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.
  6. Siller-Matula JM, Trenk D, Schrör K, et al. EPA (European Platelet Academy). Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv. 2013; 6(11): 1111–1128.
  7. Sofi F, Giusti B, Marcucci R, et al. Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis. Pharmacogenomics J. 2011; 11(3): 199–206.
  8. Winter MP, Koziński M, Kubica J, et al. Personalized antiplatelet therapy with P2Y12 receptor inhibitors: benefits and pitfalls. Post Kardiol Interw. 2015; 11(4): 259–280.
  9. Huber K. Genetic variability in response to clopidogrel therapy: clinical implications. Eur Heart J. 2010; 31(24): 2974–2976.
  10. Osnabrugge RL, Head SJ, Zijlstra F, et al. A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users. Genet Med. 2015; 17(1): 3–11.
  11. Price MJ, Berger PB, Teirstein PS, et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011; 305(11): 1097–1105.
  12. Collet JP, Cuisset T, Rangé G, et al. ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012; 367(22): 2100–2109.
  13. Samardzic J, Krpan M, Skoric B, et al. Serial clopidogrel dose adjustment after platelet function testing improves outcome of acute coronary syndrome patients undergoing percutaneous coronary intervention with high on-treatment platelet reactivity. J Thromb Thrombolysis. 2014; 38(4): 459–469.
  14. Xie X, Ma YT, Yang YN, et al. Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: a randomized control trial. Int J Cardiol. 2013; 168(4): 3736–3740.
  15. Siller-Matula JM, Gruber C, Francesconi M, et al. The net clinical benefit of personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention. Clin Sci (Lond). 2015; 128(2): 121–130.
  16. Tang Fk, Lin Lj, Hua N, et al. Earlier application of loading doses of aspirin and clopidogrel decreases rate of recurrent cardiovascular ischemic events for patients undergoing percutaneous coronary intervention. Chin Med J (Engl). 2012; 125(4): 631–638.
  17. Roberts JD, Wells GA, Le May MR, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet. 2012; 379(9827): 1705–1711.
  18. Hazarbasanov D, Velchev V, Finkov B, et al. Tailoring clopidogrel dose according to multiple electrode aggregometry decreases the rate of ischemic complications after percutaneous coronary intervention. J Thromb Thrombolysis. 2012; 34(1): 85–90.
  19. Wang XD, Zhang DF, Zhuang SW, et al. Modifying clopidogrel maintenance doses according to vasodilator-stimulated phosphoprotein phosphorylation index improves clinical outcome in patients with clopidogrel resistance. Clin Cardiol. 2011; 34(5): 332–338.
  20. Bonello L, Camoin-Jau L, Armero S, et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am J Cardiol. 2009; 103(1): 5–10.
  21. 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 randomized prospective study. J Am Coll Cardiol. 2008; 51(14): 1404–1411.
  22. Zhu HC, Li Yi, Guan SY, et al. Efficacy and safety of individually tailored antiplatelet therapy in patients with acute coronary syndrome after coronary stenting: a single center, randomized, feasibility study. J Geriatr Cardiol. 2015; 12(1): 23–29.
  23. Li Y, Han Y, Guan S, et al. Optimal- vs. standard-antiplatelet therapy on platelet function and long-term clinical outcomes in patients with high on-treatment platelet reactivity: 2-year outcomes of the multicentre, randomized Optimal-antiPlatelet Therapy (OPT) trial. Eur Heart J Suppl. 2015; 17(suppl B): B23–B31.
  24. Cayla G, Cuisset T, Silvain J, 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(10055): 2015–2022.
  25. Koltowski L, Tomaniak M, Aradi D, et al. Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective PCI patients: A pilot study: ONSIDE TEST pilot. Cardiol J. 2017; 24(3): 284–292.
  26. Breet NJ, van Werkum JW, Bouman HJ, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010; 303(8): 754–762.
  27. Aradi D, Kirtane A, Bonello L, et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J. 2015; 36(27): 1762–1771.
  28. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009; 373(9660): 309–317.
  29. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009; 360(4): 363–375.
  30. Beitelshees AL, Voora D, Lewis JP. Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics. Pharmgenomics Pers Med. 2015; 8: 43–61.
  31. Campo G, Miccoli M, Tebaldi M, et al. Genetic determinants of on-clopidogrel high platelet reactivity. Platelets. 2011; 22(6): 399–407.
  32. Shuldiner AR, O'Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009; 302(8): 849–857.
  33. Mega JL, Hochholzer W, Frelinger AL, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA. 2011; 306(20): 2221–2228.
  34. Sibbing D, Koch W, Gebhard D, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010; 121(4): 512–518.
  35. Sangkuhl K, Klein T, Altman R. Clopidogrel pathway. Pharmacogenetics and Genomics. 2010: 1.
  36. Ancrenaz V, Daali Y, Fontana P, et al. Impact of genetic polymorphisms and drug-drug interactions on clopidogrel and prasugrel response variability. Curr Drug Metab. 2010; 11(8): 667–677.
  37. Hulot JS, Bura A, Villard E, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006; 108(7): 2244–2247.
  38. Shuldiner AR, O'Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009; 302(8): 849–857.
  39. Hochholzer W, Trenk D, Fromm MF, et al. Impact of cytochrome P450 2C19 loss-of-function polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement. J Am Coll Cardiol. 2010; 55(22): 2427–2434.
  40. Fontana P, James R, Barazer I, et al. Relationship between paraoxonase-1 activity, its Q192R genetic variant and clopidogrel responsiveness in the ADRIE study. J Thromb Haemost. 2011; 9(8): 1664–1666.
  41. Lewis JP, Stephens SH, Horenstein RB, et al. The CYP2C19*17 variant is not independently associated with clopidogrel response. J Thromb Haemost. 2013; 11(9): 1640–1646.
  42. Franken CC, Kaiser AFC, Krüger JC, et al. Cytochrome P450 2B6 and 2C9 genotype polymorphism--a possible cause of prasugrel low responsiveness. Thromb Haemost. 2013; 110(1): 131–140.
  43. Cuisset T, Loosveld M, Morange PE, et al. CYP2C19*2 and *17 alleles have a significant impact on platelet response and bleeding risk in patients treated with prasugrel after acute coronary syndrome. JACC Cardiovasc Interv. 2012; 5(12): 1280–1287.
  44. Mega JL, Close SL, Wiviott SD, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010; 376(9749): 1312–1319.
  45. Taubert D, von Beckerath N, Grimberg G, et al. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther. 2006; 80(5): 486–501.
  46. Price MJ, Murray SS, Angiolillo DJ, et al. Influence of genetic polymorphisms on the effect of high- and standard-dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study. J Am Coll Cardiol. 2012; 59(22): 1928–1937.
  47. Storey RF, Melissa Thornton S, Lawrance R, et al. Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3. Platelets. 2009; 20(5): 341–348.
  48. Tantry US, Bliden KP, Wei C, et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010; 3(6): 556–566.
  49. Akerblom A, Eriksson N, Wallentin L, et al. PLATO Investigators. Polymorphism of the cystatin C gene in patients with acute coronary syndromes: Results from the PLATelet inhibition and patient Outcomes study. Am Heart J. 2014; 168(1): 96–102.e2.
  50. Varenhorst C, Eriksson N, Johansson Å, et al. Ticagrelor plasma levels but not clinical outcomes are associated with transporter and metabolism enzyme genetic polymorphisms. J Am Coll Cardiol. 2014; 63(12): A25.