We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Precision medicine in interventional cardiology: implications for antiplatelet therapy in patients undergoing percutaneous coronary intervention

    Mattia Galli

    Catholic University of the Sacred Heart, Rome, Italy

    Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy

    ,
    Luis Ortega-Paz

    Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL 32209, USA

    ,
    Francesco Franchi

    Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL 32209, USA

    ,
    Fabiana Rollini

    Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL 32209, USA

    &
    Dominick J Angiolillo

    *Author for correspondence: Tel.: +1 904 244 3933;

    E-mail Address: dominick.angiolillo@jax.ufl.edu

    Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL 32209, USA

    Published Online:https://doi.org/10.2217/pgs-2022-0057

    Precision medicine is a medical model that proposes the customization of medical treatments to the individual patient, as opposed to a one-drug-fits-all model. Such a “personalized medicine” approach has been widely adopted in several medical fields, such as cancer medicine, but the implementation of precision medicine in cardiovascular medicine has not been similarly straightforward. Because pharmacogenomics plays an important role in the safety and efficacy of cardiovascular drug therapy, there has been a great interest in the use of tools aiming at personalizing antiplatelet therapy. Moreover, antiplatelet therapy is essential for the treatment of cardiovascular patients to reduce the risk of thrombotic complications, particularly those undergoing percutaneous coronary intervention, but it is inevitably associated with increased bleeding risk. In this review, the authors discuss the rationale, summarize the evidence and discuss the current and future directions for the personalization of antiplatelet treatment regimens in patients undergoing percutaneous coronary intervention.

    References

    • 1. Council NR. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. The National Academies Press, DC, USA,142 (2011).
    • 2. Incorvati JA, Shah S, Mu Y, Lu J. Targeted therapy for HER2 positive breast cancer. J. Hematol. Onco 6, 38 (2013).
    • 3. Duarte JD, Cavallari LH. Pharmacogenetics to guide cardiovascular drug therapy. Nat. Rev. Cardiol. 18(9), 649–665 (2021).
    • 4. Galli M, Franchi F, Rollini F, Angiolillo DJ. Role of platelet function and genetic testing in patients undergoing percutaneous coronary intervention. Trends Cardiovasc. Med. S1050-1738(21) 00157-2 (2021).
    • 5. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ. ACC/AHA versus ESC guidelines on dual antiplatelet therapy: JACC guideline comparison. J. Am. Coll. Cardiol. 72(23 Pt A), 2915–2931 (2018).
    • 6. Collet J-P, Thiele H, Barbato E et al. 2020 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 in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur. Heart J. 42(14), 1289–1367 (2020).
    • 7. Angiolillo DJ, Galli M, Collet JP, Kastrati A, O'Donghue M. Antiplatelet therapy after percutaneous coronary intervention. Eurointervention. 17(17), e1371–e1396 (2022).
    • 8. Valgimigli M, Costa F, Lokhnygina Y et al. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial. Eur. Heart J. 38(11), 804–810 (2017).
    • 9. Galli M, Andreotti F, D'Amario D et al. Antithrombotic therapy in the early phase of non-ST-elevation acute coronary syndromes: a systematic review and meta-analysis. Eur. Heart J. Cardiovasc. Pharmacother. 6(1), 43–56 (2020).
    • 10. 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. 36(27), 1762–1771 (2015).
    • 11. Sibbing D, Aradi D, Alexopoulos D et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y(12) receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc. Interv. 12(16), 1521–1537 (2019).
    • 12. Galli M, Franchi F, Rollini F et al. Genetic testing in patients undergoing percutaneous coronary intervention: rationale, evidence and practical recommendations. Expert Rev. Clin. Pharmacol. 14(8), 963–978 (2021).
    • 13. Galli M, Benenati S, Franchi F et al. Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials. Eur. Heart J. 43(10), 959–967 (2022).
    • 14. Galli M, Capodanno D, Andreotti F, Crea F, Angiolillo DJ. Safety and efficacy of P2Y(12) inhibitor monotherapy in patients undergoing percutaneous coronary interventions. Expert Opin. Drug Saf. 20(1), 9–21 (2021).
    • 15. Ibanez B, James S, Agewall S et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur. Heart J. 39(2), 119–177 (2018).
    • 16. Neumann FJ, Sousa-Uva M, Ahlsson A et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur. Heart J. 40(2), 87–165 (2019).
    • 17. Scott SA, Sangkuhl K, Stein CM et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin. Pharmacol. Ther. 94(3), 317–323 (2013).
    • 18. Lee CR, Luzum JA, Sangkuhl K et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin. Pharmacol. Ther. doi:10.1002/cpt.2526 (2022) (Epub ahead of print).
    • 19. Galli M, Gargiulo G. Towards a personalized selection of antithrombotic agents in patients undergoing PCI: the role of clinical presentation in tools for risk assessment. J. Thromb. Thrombolysis 53(2), 495–498 (2022).
    • 20. Giustino G, Chieffo A, Palmerini T et al. Efficacy and safety of dual antiplatelet therapy after complex PCI. J. Am. Coll. Cardiol. 68(17), 1851–1864 (2016).
    • 21. Capodanno D, Bhatt DL, Gibson CM et al. Bleeding avoidance strategies in percutaneous coronary intervention. Nat. Rev. Cardiol. 19(2), 117–132 (2021).
    • 22. Capodanno D, Morice MC, Angiolillo DJ et al. Trial design principles for patients at high bleeding risk undergoing PCI: JACC Scientific Expert Panel. J. Am. Coll. Cardiol. 76(12), 1468–1483 (2020).
    • 23. Bhatt DL, Kaski JC, Delaney S et al. Results of an international crowdsourcing survey on the treatment of non-ST segment elevation ACS patients at high-bleeding risk undergoing percutaneous intervention. Int. J. Cardiol. 337, 1–8 (2021).
    • 24. Li-Wan-Po A, Girard T, Farndon P, Cooley C, Lithgow J. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br. J. Clin. Pharmacol. 69(3), 222–230 (2010).
    • 25. Pereira NL, Rihal CS, So DYF et al. Clopidogrel pharmacogenetics. Circulation Cardiovascular Interventions 12(4), e007811 (2019).
    • 26. Moon JY, Franchi F, Rollini F et al. Role of genetic testing in patients undergoing percutaneous coronary intervention. Expert Rev. Clin. Pharmacol. 11(2), 151–164 (2018).
    • 27. Mega JL, Close SL, Wiviott SD et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N. Engl. J. Med. 360(4), 354–362 (2009).
    • 28. Mega JL, Simon T, Collet JP et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 304(16), 1821–1830 (2010).
    • 29. 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. 302(8), 849–857 (2009).
    • 30. Simon T, Verstuyft C, Mary-Krause M et al. Genetic determinants of response to clopidogrel and cardiovascular events. N. Engl. J. Med. 360(4), 363–375 (2009).
    • 31. 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. 55(22), 2427–2434 (2010).
    • 32. Lewis JP, Stephens SH, Horenstein RB et al. The CYP2C19*17 variant is not independently associated with clopidogrel response. J. Thromb. Haemost. 11(9), 1640–1646 (2013).
    • 33. Lee CR, Thomas CD, Beitelshees AL et al. Impact of the CYP2C19*17 allele on outcomes in patients receiving genotype-guided antiplatelet therapy after percutaneous coronary intervention. Clin. Pharmacol. Ther. 109(3), 705–715 (2021).
    • 34. Wallentin L, James S, Storey RF et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet. 376(9749), 1320–1328 (2010).
    • 35. Mega JL, Close SL, Wiviott SD et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 119(19), 2553–2560 (2009).
    • 36. Sugidachi A, Ogawa T, Kurihara A et al. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel's active metabolite. J. Thromb. Haemost. 5(7), 1545–1551 (2007).
    • 37. Trenk D, Hochholzer W. Genetics of platelet inhibitor treatment. Br. J. Clin. Pharmacol. 77(4), 642–653 (2014).
    • 38. Capodanno D, Dharmashankar K, Angiolillo DJ. Mechanism of action and clinical development of ticagrelor, a novel platelet ADP P2Y12 receptor antagonist. Expert Rev. Cardiovasc. Ther. 8(2), 151–158 (2010).
    • 39. Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circulation J. 74(4), 597–607 (2010).
    • 40. Capodanno D, Angiolillo DJ. Antithrombotic therapy for atherosclerotic cardiovascular disease risk mitigation in patients with coronary artery disease and diabetes mellitus. Circulation 142(22), 2172–2188 (2020).
    • 41. Patti G, Cavallari I, Andreotti F et al. Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs. Nat. Rev. Cardiol. 16(2), 113–130 (2019).
    • 42. Rollini F, Franchi F, Muñiz-Lozano A, Angiolillo DJ. Platelet function profiles in patients with diabetes mellitus. J. Cardiovasc. Transl. Res. 6(3), 329–345 (2013).
    • 43. Franchi F, Rollini F, Aggarwal N et al. Pharmacodynamic comparison of prasugrel versus ticagrelor in patients with Type 2 diabetes mellitus and coronary artery disease: the OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 study. Circulation. 134(11), 780–792 (2016).
    • 44. Angiolillo DJ, Jakubowski JA, Ferreiro JL et al. Impaired responsiveness to the platelet P2Y12 receptor antagonist clopidogrel in patients with Type 2 diabetes and coronary artery disease. J. Am. Coll. Cardiol. 64(10), 1005–1014 (2014).
    • 45. Zhu HJ, Wang X, Gawronski BE, Brinda BJ, Angiolillo DJ, Markowitz JS. Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation. J. Pharmacol. Exp. Ther. 344(3), 665–672 (2013).
    • 46. Yao H, Gu J, Shan Y et al. Type 2 diabetes mellitus decreases systemic exposure of clopidogrel active metabolite through upregulation of P-glycoprotein in rats. Biochem. Pharmacol. 180, 114142 (2020).
    • 47. Gravel S, Chiasson JL, Turgeon J, Grangeon A, Michaud V. Modulation of CYP450 activities in patients with Type 2 diabetes. Clin. Pharmacol. Ther. 106(6), 1280–1289 (2019).
    • 48. Erlinge D, Varenhorst C, Braun OO et al. Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J. Am. Coll. Cardiol. 52(24), 1968–1977 (2008).
    • 49. Ferreiro JL, Angiolillo DJ. Diabetes and antiplatelet therapy in acute coronary syndrome. Circulation. 123(7), 798–813 (2011).
    • 50. Zhang R, Mamza JB, Morris T et al. Lifetime risk of cardiovascular-renal disease in Type 2 diabetes: a population-based study in 473,399 individuals. BMC Medicine. 20(1), 63 (2022).
    • 51. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al. Clopidogrel withdrawal is associated with proinflammatory and prothrombotic effects in patients with diabetes and coronary artery disease. Diabetes. 55(3), 780–784 (2006).
    • 52. Angiolillo DJ, Bernardo E, Sabaté M et al. Impact of platelet reactivity on cardiovascular outcomes in patients with Type 2 diabetes mellitus and coronary artery disease. J. Am. Coll. Cardiol. 50(16), 1541–1547 (2007).
    • 53. Franchi F, James SK, Lakic TG et al. Impact of diabetes mellitus and chronic kidney disease on cardiovascular outcomes and platelet P2Y(12) receptor antagonist effects in patients with acute coronary syndromes: insights from the PLATO trial. J. Am. Heart Association 8(6), e011139 (2019).
    • 54. Wiviott SD, Braunwald E, Angiolillo DJ et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel – Thrombolysis in Myocardial Infarction 38. Circulation. 118(16), 1626–1636 (2008).
    • 55. Steg PG, Bhatt DL, Simon T et al. Ticagrelor in patients with stable coronary disease and diabetes. N. Engl. J. Med. 381(14), 1309–1320 (2019).
    • 56. Bhatt DL, Bonaca MP, Bansilal S et al. Reduction in ischemic events with ticagrelor in diabetic patients with prior myocardial infarction in PEGASUS-TIMI 54. J. Am. Coll. Cardiol. 67(23), 2732–2740 (2016).
    • 57. Nardin M, Verdoia M, Sartori C et al. Body mass index and platelet reactivity during dual antiplatelet therapy with clopidogrel or ticagrelor. J. Cardiovasc. Pharmacol. 66(4), 364–370 (2015).
    • 58. Baber U, Mehran R, Kirtane AJ et al. Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry. Circ. Cardiovasc. Interv. 8(6), e001683 (2015).
    • 59. Park DW, Ahn JM, Song HG et al. Differential prognostic impact of high on-treatment platelet reactivity among patients with acute coronary syndromes versus stable coronary artery disease undergoing percutaneous coronary intervention. Am. Heart J. 165(1), 34–42.e1 (2013).
    • 60. Angiolillo DJ, Capodanno D, Danchin N et al. Derivation, validation, and prognostic utility of a prediction rule for nonresponse to clopidogrel: the ABCD-GENE score. JACC Cardiovas. Interv. 13(5), 606–617 (2020).
    • 61. Capodanno D, Angiolillo DJ, Lennon RJ et al. ABCD-GENE score and clinical outcomes following percutaneous coronary intervention: insights from the TAILOR-PCI trial. J. Am. Heart Association 11(4), e024156 (2022).
    • 62. Dai L, Xu J, Yan H et al. Application of age, body mass index, chronic kidney disease, diabetes, and genotyping score for efficacy of clopidogrel: secondary analysis of the CHANCE trial. Stroke. 53(2), 465–472 (2022).
    • 63. Man M, Farmen M, Dumaual C et al. Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans. J. Clin. Pharmacol. 50(8), 929–940 (2010).
    • 64. Alrajeh KY, Roman YM. The frequency of major CYP2C19 genetic polymorphisms in women of Asian, Native Hawaiian and Pacific Islander subgroups. Personalized Med. 19(4), 327–339 (2022).
    • 65. Kwon O, Park D-W. Antithrombotic therapy after acute coronary syndromes or percutaneous coronary interventions in East Asian populations. JACC. 2(1), 1–18 (2022).
    • 66. Kim HK, Tantry US, Smith SC Jr et al. The East Asian paradox: an updated position statement on the challenges to the current antithrombotic strategy in patients with cardiovascular disease. Thromb. Haemost. 121(4), 422–432 (2021).
    • 67. Levine GN, Jeong YH, Goto S et al. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat. Rev. Cardiol. 11(10), 597–606 (2014).
    • 68. Valgimigli M, Gragnano F, Branca M et al. P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials. BMJ (Clin. Res. Ed.) 373, n1332 (2021).
    • 69. Gustafson C, Gower MN, Williams AK et al. Effect of gender on clinical outcomes in patients receiving CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. Circulation. 13(5), 554–556 (2020).
    • 70. Franchi F, Rollini F, Cho JR, Ferrante E, Angiolillo DJ. Platelet function testing in contemporary clinical and interventional practice. Curr. Treat. Options Cardiovasc. Med. 16(5), 300 (2014).
    • 71. Angiolillo DJ. Dual antiplatelet therapy guided by platelet function testing. Lancet. 390(10104), 1718–1720 (2017).
    • 72. Galli M, Franchi F. Guided selection of antiplatelet therapy in acute coronary syndrome: impact on outcomes and resources utilization. Int. J. Cardiol. 345, 36–38 (2021).
    • 73. Claassens DMF, Vos GJA, Bergmeijer TO et al. A genotype-guided strategy for oral P2Y(12) inhibitors in primary PCI. N. Engl. J. Med. 381(17), 1621–1631 (2019).
    • 74. Sibbing D, Aradi D, Jacobshagen C et al. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 390(10104), 1747–1757 (2017).
    • 75. Galli M, Benenati S, Capodanno D et al. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Lancet. 397(10283), 1470–1483 (2021).
    • 76. Cadroy Y, Bossavy JP, Thalamas C, Sagnard L, Sakariassen K, Boneu B. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans. Circulation. 101(24), 2823–2828 (2000).
    • 77. Hindricks G, Potpara T, Dagres N et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 42(5), 373–498 (2020).
    • 78. Gibson CM, Mehran R, Bode C et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N. Engl. J. Med. 375(25), 2423–2434 (2016).
    • 79. Cannon CP, Bhatt DL, Oldgren J et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N. Engl. J. Med. 377(16), 1513–1524 (2017).
    • 80. Lopes RD, Heizer G, Aronson R et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N. Engl. J. Med. 380(16), 1509–1524 (2019).
    • 81. Vranckx P, Valgimigli M, Eckardt L et al. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet. 394(10206), 1335–1343 (2019).
    • 82. Galli M, Andreotti F, D'Amario D et al. Randomised trials and meta-analyses of double vs triple antithrombotic therapy for atrial fibrillation-ACS/PCI: a critical appraisal. Int. J. Cardiol. Heart Vasculature 28, 100524 (2020).
    • 83. Capodanno D, Di Maio M, Greco A et al. Safety and efficacy of double antithrombotic therapy with non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention: a systematic review and meta-analysis. J. Am. Heart Association 9(16), e017212 (2020).
    • 84. Gargiulo G, Goette A, Tijssen J et al. Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials. Eur. Heart J. 40(46), 3757–3767 (2019).
    • 85. Galli M, Andreotti F, D'Amario D et al. Dual therapy with direct oral anticoagulants significantly increases the risk of stent thrombosis compared to triple therapy. Eur. Heart J. Cardiovasc. Pharmacother. 6(2), 128–129 (2020).
    • 86. Galli M, Andreotti F, Porto I, Crea F. Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients. Europace. 22(4), 538–546 (2020).
    • 87. Galli M, Andreotti F, D'Amario D, Porto I, Crea F. Stent thrombosis with dual antithrombotic therapy in atrial fibrillation-ACS/PCI trials. J. Am. Coll. Cardiol. 75(14), 1727–1728 (2020).
    • 88. Schömig A, Neumann FJ, Kastrati A et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N. Engl. J. Med. 334(17), 1084–1089 (1996).
    • 89. Leon MB, Baim DS, Popma JJ et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent anticoagulation restenosis study investigators. N. Engl. J. Med. 339(23), 1665–1671 (1998).
    • 90. O'Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of aspirin discontinuation on a background of a P2Y(12) inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation. 142(6), 538–545 (2020).
    • 91. Benenati S, Galli M, De Marzo V et al. Very short vs. long dual antiplatelet therapy after second generation drug-eluting stents in 35 785 patients undergoing percutaneous coronary interventions: a meta-analysis of randomized controlled trials. Eur. Heart J. Cardiovasc. Pharmacother. 7(2), 86–93 (2021).
    • 92. Watanabe H, Morimoto T, Natsuaki M et al. Comparison of clopidogrel monotherapy after 1 to 2months of dual antiplatelet therapy with 12months of dual antiplatelet therapy in patients with acute coronary syndrome: the STOPDAPT-2 ACS randomized clinical trial. JAMA Cardiology. 7(4), 407–417 (2022).
    • 93. De Luca L, D'Ascenzo F, Musumeci G et al. Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry. Eurointervention. 13(4), 459–466 (2017).
    • 94. Franchi F, Rollini F, Rivas Rios J et al. Pharmacodynamic effects of switching from ticagrelor to clopidogrel in patients with coronary artery disease: results of the SWAP-4 study. Circulation. 137(23), 2450–2462 (2018).
    • 95. Cuisset T, Deharo P, Quilici J et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (Timing of Platelet Inhibition after acute coronary syndrome) randomized study. Eur. Heart J. 38(41), 3070–3078 (2017).
    • 96. Kim H-S, Kang J, Hwang D et al. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial. Lancet. 396(10257), 1079–1089 (2020).
    • 97. Kim CJ, Park MW, Kim MC et al. Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial. Lancet. 398(10308), 1305–1316 (2021).