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  • Review Article
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P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention

Nature Reviews Cardiology volume 19, pages 829–844 (2022)Cite this article

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Abstract

For 20 years, dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and a platelet P2Y12 receptor inhibitor, has been the gold standard of antithrombotic pharmacology after percutaneous coronary intervention (PCI). In the past 5 years, several investigations have challenged this paradigm by testing the efficacy and safety of P2Y12 inhibitor monotherapy (that is, without aspirin) following a short course of DAPT. Collectively, these studies suggested a reduction in the risk of major bleeding and no significant increase in thrombotic or ischaemic events compared with guideline-recommended DAPT. Current recommendations are evolving to inform clinical practice on the ideal candidates for P2Y12 inhibitor monotherapy after PCI. Generalizing the results of studies of P2Y12 inhibitor monotherapy requires a thorough understanding of their design, populations, interventions, comparators and results. In this Review, we provide an up-to-date overview on the use of P2Y12 inhibitor monotherapy after PCI, including supporting pharmacodynamic and clinical evidence, practical recommendations and future directions.

Key points

  • The duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) that is currently recommended in European and US guidelines is 6 months for patients with chronic coronary syndromes and 12 months for patients with acute coronary syndromes (ACS).

  • Several trials have investigated alternative strategies to increase the safety of antithrombotic protection after PCI; one strategy is to reduce the duration of DAPT to 1 or 3 months in patients with chronic coronary syndromes and 3–6 months in patients with ACS.

  • To reduce the duration of DAPT, a wealth of evidence is emerging that supports the discontinuation of aspirin and the continuation of P2Y12 inhibitor monotherapy in the long term.

  • Discontinuing aspirin rather than the P2Y12 inhibitor at the time of transitioning from DAPT to single antiplatelet therapy is an appealing option for clinical practice that is now endorsed by clinical guidelines in both Europe and the USA.

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Fig. 1: Platelet activation mechanisms.
Fig. 2: Clinical investigations of P2Y12 inhibitor monotherapy versus aspirin.
Fig. 3: Timeline of randomized controlled trials of P2Y12 inhibitor monotherapy after PCI.
Fig. 4: Antiplatelet therapy after undergoing PCI with drug-eluting stents.

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References

  1. Valgimigli, M. et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur. Heart J. 39, 213–260 (2018).

    Article  PubMed  Google Scholar 

  2. Levine, G. N. 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. 68, 1082–1115 (2016).

    Article  PubMed  Google Scholar 

  3. Neumann, F.-J. et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur. Heart J. 40, 87–165 (2019).

    Article  PubMed  Google Scholar 

  4. Lawton, J. S. et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145, e18–e114 (2022).

    PubMed  Google Scholar 

  5. Angiolillo, D. A., Galli, M., Collet, J.-P., Kastrati, A. & O’Donoghue, M. O. Antiplatelet therapy after percutaneous coronary intervention. EuroIntervention 17, e1371–e1396 (2022).

    Article  PubMed  Google Scholar 

  6. Palmerini, T. et al. Stent thrombosis with drug-eluting stents. J. Am. Coll. Cardiol. 62, 1915–1921 (2013).

    Article  CAS  PubMed  Google Scholar 

  7. Stone, G. W. et al. A prospective natural-history study of coronary atherosclerosis. N. Engl. J. Med. 364, 226–235 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Bonaca, M. P. et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N. Engl. J. Med. 372, 1791–1800 (2015).

    Article  PubMed  Google Scholar 

  9. Cao, D., Chandiramani, R., Chiarito, M., Claessen, B. E. & Mehran, R. Evolution of antithrombotic therapy in patients undergoing percutaneous coronary intervention: a 40-year journey. Eur. Heart J. 42, 339–351 (2021).

    Article  PubMed  Google Scholar 

  10. Capodanno, D., Alfonso, F., Levine, G. N., Valgimigli, M. & Angiolillo, D. J. ACC/AHA versus ESC guidelines on dual antiplatelet therapy. J. Am. Coll. Cardiol. 72, 2915–2931 (2018).

    Article  PubMed  Google Scholar 

  11. Moon, J. Y., Franchi, F., Rollini, F. & Angiolillo, D. J. Evolution of coronary stent technology and implications for duration of dual antiplatelet therapy. Prog. Cardiovasc. Dis. 60, 478–490 (2018).

    Article  PubMed  Google Scholar 

  12. Capodanno, D. et al. Bleeding avoidance strategies in percutaneous coronary intervention. Nat. Rev. Cardiol. 19, 117–132 (2022).

    Article  PubMed  Google Scholar 

  13. Knuuti, J. et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur. Heart J. 41, 407–477 (2020).

    Article  PubMed  Google Scholar 

  14. Collet, J.-P. et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur. Heart J. 42, 1289–1367 (2021).

    Article  PubMed  Google Scholar 

  15. Capodanno, D. et al. Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention. Nat. Rev. Cardiol. 15, 480–496 (2018).

    Article  CAS  PubMed  Google Scholar 

  16. Tomaniak, M., Storey, R. F. & Serruys, P. W. Aspirin-free antiplatelet regimens after PCI: when is it best to stop aspirin and who could ultimately benefit? EuroIntervention 15, 1125–1129 (2020).

    Article  PubMed  Google Scholar 

  17. Antithrombotic Trialists’ (ATT) Collaboration et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373, 1849–1860 (200).

  18. Armstrong, P. C. J. et al. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J. Thromb. Haemost. 9, 552–561 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cadroy, Y. et al. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans. Circulation 101, 2823–2828 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Storey, R. F. et al. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. Br. J. Haematol. 110, 925–934 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Johnson, T. W. et al. Pharmacodynamic comparison of ticagrelor monotherapy versus ticagrelor and aspirin in patients after percutaneous coronary intervention: the TEMPLATE (ticagrelor monotherapy and platelet reactivity) randomized controlled trial. J. Am. Heart Assoc. 9, e016495 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Baber, U. et al. Ticagrelor with or without aspirin after PCI: the TWILIGHT platelet substudy. J. Am. Coll. Cardiol. 75, 578–586 (2020).

    Article  CAS  PubMed  Google Scholar 

  23. Hennigan, B. W. et al. Recovery of platelet reactivity following cessation of either aspirin or ticagrelor in patients treated with dual antiplatelet therapy following percutaneous coronary intervention: a GLOBAL LEADERS substudy. Platelets 33, 141–146 (2022).

    Article  CAS  PubMed  Google Scholar 

  24. Franchi, F. et al. Pharmacodynamic effects of vorapaxar in patients with and without diabetes mellitus: results of the OPTIMUS-5 study. JACC Basic. Transl. Sci. 4, 763–775 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Capodanno, D. & Angiolillo, D. J. When less becomes more: insights on the pharmacodynamic effects of aspirin withdrawal in patients with potent platelet P2Y12 inhibition induced by ticagrelor. J. Am. Heart Assoc. 9, e019432 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Stone, G. W. et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 382, 614–623 (2013).

    Article  PubMed  Google Scholar 

  27. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348, 1329–1339 (1996).

    Article  Google Scholar 

  28. Bhatt, D. L., Hirsch, A. T., Ringleb, P. A., Hacke, W. & Topol, E. J. Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin. Am. Heart J. 140, 67–73 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Bhatt, D. L. et al. Amplified benefit of clopidogrel versus aspirin in patients with diabetes mellitus. Am. J. Cardiol. 90, 625–628 (2002).

    Article  PubMed  Google Scholar 

  30. Ringleb, P. A. et al. Benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events. Stroke 35, 528–532 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Bhatt, D. L. et al. Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation 103, 363–368 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Hirsh, J. & Bhatt, D. L. Comparative benefits of clopidogrel and aspirin in high-risk patient populations. Arch. Intern. Med. 164, 2106–2110 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Chiarito, M. et al. Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis. Lancet 395, 1487–1495 (2020).

    Article  PubMed  Google Scholar 

  34. Koo, B.-K. et al. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet 397, 2487–2496 (2021).

    Article  CAS  PubMed  Google Scholar 

  35. Kim, H. K. 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, 422–432 (2021).

    Article  PubMed  Google Scholar 

  36. Vranckx, P. et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet 392, 940–949 (2018).

    Article  CAS  PubMed  Google Scholar 

  37. Chichareon, P. et al. DAPT score and the impact of ticagrelor monotherapy during the second year after PCI. JACC Cardiovasc. Interv. 13, 634–646 (2020).

    Article  PubMed  Google Scholar 

  38. Ono, M. et al. Ticagrelor monotherapy versus aspirin monotherapy at 12 months after percutaneous coronary intervention: a landmark analysis of the GLOBAL LEADERS trial. EuroIntervention https://doi.org/10.4244/EIJ-D-21-00870 (2022).

    Article  PubMed  Google Scholar 

  39. Angiolillo, D. J. et al. Variability in individual responsiveness to clopidogrel. J. Am. Coll. Cardiol. 49, 1505–1516 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Angiolillo, D. J. et al. Derivation, validation, and prognostic utility of a prediction rule for nonresponse to clopidogrel: the ABCD-GENE score. JACC Cardiovasc. Interv. 13, 606–617 (2020).

    Article  PubMed  Google Scholar 

  41. Sibbing, D. et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc. Interv. 12, 1521–1537 (2019).

    Article  PubMed  Google Scholar 

  42. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04418479 (2022).

  43. Han, Y. et al. Magnetically-controlled capsule endoscopy for assessment of antiplatelet therapy-induced gastrointestinal injury. J. Am. Coll. Cardiol. 79, 116–128 (2022).

    Article  CAS  PubMed  Google Scholar 

  44. Gragnano, F. et al. Ticagrelor monotherapy or dual antiplatelet therapy after drug-eluting stent implantation: per-protocol analysis of the GLOBAL LEADERS trial. J. Am. Heart Assoc. 10.1161/JAHA.121.024291 (2022).

  45. Serruys, P. W. et al. Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the Global Leaders trial. Eur. Heart J. 40, 2595–2604 (2019).

    Article  CAS  PubMed  Google Scholar 

  46. Takahashi, K. et al. Efficacy and safety of ticagrelor monotherapy in patients undergoing multivessel PCI. J. Am. Coll. Cardiol. 74, 2015–2027 (2019).

    Article  PubMed  Google Scholar 

  47. Takahashi, K. et al. Impact of ticagrelor monotherapy on two-year clinical outcomes in patients with long stenting: a post hoc analysis of the GLOBAL LEADERS trial. EuroIntervention 16, 634–644 (2020).

    Article  PubMed  Google Scholar 

  48. Takahashi, K. et al. Efficacy and safety of one-month DAPT followed by 23-month ticagrelor monotherapy in patients undergoing proximal LAD stenting: insights from the GLOBAL LEADERS trial. Int. J. Cardiol. 320, 27–34 (2020).

    Article  PubMed  Google Scholar 

  49. Gao, C. et al. Ticagrelor monotherapy in patients with concomitant diabetes mellitus and chronic kidney disease: a post hoc analysis of the GLOBAL LEADERS trial. Cardiovasc. Diabetol. 19, 179 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ono, M. et al. Impact of white blood cell count on clinical outcomes in patients treated with aspirin-free ticagrelor monotherapy after percutaneous coronary intervention: insights from the GLOBAL LEADERS trial. Eur. Heart J. Cardiovasc. Pharmacother. 8, 39–47 (2022).

    Article  PubMed  Google Scholar 

  51. Tomaniak, M. et al. Benefit and risks of aspirin in addition to ticagrelor in acute coronary syndromes. JAMA Cardiol. 4, 1092–1101 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Vranckx, P. et al. Efficacy and safety of ticagrelor monotherapy by clinical presentation: pre-specified analysis of the GLOBAL LEADERS trial. J. Am. Heart Assoc. 10, e015560 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Gamal Setih, A. et al. Efficacy and safety of early aspirin withdrawal and continuation of ticagrelor monotherapy post PCI for STEMI. A post hoc analysis of the randomized global leaders trial. Eur. Heart J. 42 (Suppl. 1), ehab724.2998 (2021).

    Article  Google Scholar 

  54. Wang, R. et al. Aspirin-free antiplatelet regimens after PCI: insights from the GLOBAL LEADERS trial and beyond. Eur. Heart J. Cardiovasc. Pharmacother. 7, 547–556 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Franzone, A. et al. Ticagrelor alone versus dual antiplatelet therapy from 1 month after drug-eluting coronary stenting. J. Am. Coll. Cardiol. 74, 2223–2234 (2019).

    Article  CAS  PubMed  Google Scholar 

  56. Franzone, A. et al. Ticagrelor alone or conventional dual antiplatelet therapy in patients with stable or acute coronary syndromes. EuroIntervention 16, 627–633 (2020).

    Article  PubMed  Google Scholar 

  57. Mehran, R. et al. Ticagrelor with or without aspirin in high-risk patients after PCI. N. Engl. J. Med. 381, 2032–2042 (2019).

    Article  CAS  PubMed  Google Scholar 

  58. Vogel, B. et al. Sex differences among patients with high risk receiving ticagrelor with or without aspirin after percutaneous coronary intervention: a subgroup analysis of the TWILIGHT randomized clinical trial. JAMA Cardiol. 6, 1032–1041 (2021).

    Article  PubMed  Google Scholar 

  59. Angiolillo, D. J. et al. Impact of age on the safety and efficacy of ticagrelor monotherapy in patients undergoing PCI. JACC Cardiovasc. Interv. 14, 1434–1446 (2021).

    Article  PubMed  Google Scholar 

  60. Dangas, G. et al. Safety and efficacy of ticagrelor monotherapy according to drug-eluting stent type: the TWILIGHT-STENT study. EuroIntervention 17, 1330–1339 (2022).

    Article  PubMed  Google Scholar 

  61. Han, Y. et al. Ticagrelor with or without aspirin in chinese patients undergoing percutaneous coronary intervention: a TWILIGHT China substudy. Circ. Cardiovasc. Interv. 15, e009495 (2022).

    Article  CAS  PubMed  Google Scholar 

  62. Angiolillo, D. J. et al. Ticagrelor with or without aspirin in high-risk patients with diabetes mellitus undergoing percutaneous coronary intervention. J. Am. Coll. Cardiol. 75, 2403–2413 (2020).

    Article  CAS  PubMed  Google Scholar 

  63. Stefanini, G. G. et al. Ticagrelor monotherapy in patients with chronic kidney disease undergoing percutaneous coronary intervention: TWILIGHT-CKD. Eur. Heart J. 42, 4683–4693 (2021).

    Article  CAS  PubMed  Google Scholar 

  64. Dehghani, P. et al. Ticagrelor monotherapy after PCI in patients with concomitant diabetes mellitus and chronic kidney disease: TWILIGHT DM-CKD. Eur. Heart J. Cardiovasc. Pharmacother. https://doi.org/10.1093/ehjcvp/pvac016 (2022).

    Article  PubMed  Google Scholar 

  65. Chiarito, M. et al. Ticagrelor monotherapy after PCI in high-risk patients with prior MI: a prespecified TWILIGHT substudy. JACC Cardiovasc. Interv. 15, 282–293 (2022).

    Article  PubMed  Google Scholar 

  66. Dangas, G. et al. Ticagrelor with aspirin or alone after complex PCI: the TWILIGHT-COMPLEX analysis. J. Am. Coll. Cardiol. 75, 2414–2424 (2020).

    Article  CAS  PubMed  Google Scholar 

  67. Escaned, J. et al. Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR. Eur. Heart J. 42, 4624–4634 (2021).

    Article  CAS  PubMed  Google Scholar 

  68. Baber, U. et al. Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS. Eur. Heart J. 41, 3533–3545 (2020).

    Article  CAS  PubMed  Google Scholar 

  69. Kim, B.-K. et al. Effect of ticagrelor monotherapy vs ticagrelor with aspirin on major bleeding and cardiovascular events in patients with acute coronary syndrome. JAMA 323, 2407–2416 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kim, B. G. et al. Age-dependent effect of ticagrelor monotherapy versus ticagrelor with aspirin on major bleeding and cardiovascular events: a post hoc analysis of the TICO randomized trial. J. Am. Heart Assoc. 10, e022700 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yun, K. H. et al. Ischemic and bleeding events of ticagrelor monotherapy in Korean patients with and without diabetes mellitus: insights from the TICO trial. Front. Pharmacol. 11, 620906 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Lee, S.-J. et al. Ticagrelor monotherapy versus ticagrelor with aspirin in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc. Interv. 14, 431–440 (2021).

    Article  PubMed  Google Scholar 

  73. Cho, J. Y. et al. Factors related to major bleeding after ticagrelor therapy: results from the TICO trial. J. Am. Heart Assoc. 10, e019630 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Dewilde, W. J. et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 381, 1107–1115 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. Gibson, C. M. et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N. Engl. J. Med. 375, 2423–2434 (2016).

    Article  CAS  PubMed  Google Scholar 

  76. Cannon, C. P. et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N. Engl. J. Med. 377, 1513–1524 (2017).

    Article  CAS  PubMed  Google Scholar 

  77. Lopes, R. D. et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N. Engl. J. Med. 380, 1509–1524 (2019).

    Article  CAS  PubMed  Google Scholar 

  78. Vranckx, P. 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, 1335–1343 (2019).

    Article  CAS  PubMed  Google Scholar 

  79. Hahn, J.-Y. et al. Effect of P2Y12 inhibitor monotherapy vs dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention: the SMART-CHOICE randomized clinical trial. JAMA 321, 2428–2437 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Yun, K. H. et al. Safety of 3-month dual antiplatelet therapy after implantation of ultrathin sirolimus-eluting stents with biodegradable polymer (Orsiro): results from the SMART-CHOICE trial. J. Am. Heart Assoc. 10, e018366 (2021).

    Article  PubMed  Google Scholar 

  81. Roh, J. W. et al. P2Y12 inhibitor monotherapy in complex percutaneous coronary intervention: a post-hoc analysis of SMART-CHOICE randomized clinical trial. Cardiol. J. 28, 855–863 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Lee, S. H. et al. Clopidogrel monotherapy in patients with and without on-treatment high platelet reactivity: a SMART-CHOICE sub-study. EuroIntervention 17, e888–e897 (2021).

    Article  PubMed  Google Scholar 

  83. Watanabe, H. et al. Effect of 1-month dual antiplatelet therapy followed by clopidogrel vs 12-month dual antiplatelet therapy on cardiovascular and bleeding events in patients receiving PCI: the STOPDAPT-2 randomized clinical trial. JAMA 321, 2414–2427 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kanenawa, K. et al. Patient selection and clinical outcomes in the STOPDAPT-2 trial. Circ. Cardiovasc. Interv. 14, e010007 (2021).

    Article  PubMed  Google Scholar 

  85. Yamamoto, K. et al. Very short dual antiplatelet therapy after drug-eluting stent implantation in patients who underwent complex percutaneous coronary intervention: insight from the STOPDAPT-2 trial. Circ. Cardiovasc. Interv. 14, e010384 (2021).

    Article  PubMed  Google Scholar 

  86. Watanabe, H. et al. Very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk. Circulation 140, 1957–1959 (2019).

    Article  PubMed  Google Scholar 

  87. Watanabe, H. et al. Details on the effect of very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk: insight from the STOPDAPT-2 trial. Cardiovasc. Interv. Ther. 36, 91–103 (2021).

    Article  PubMed  Google Scholar 

  88. Watanabe, H. et al. Influence of CYP2C19 genotypes for the effect of 1-month dual antiplatelet therapy followed by clopidogrel monotherapy relative to 12-month dual antiplatelet therapy on clinical outcomes after percutaneous coronary intervention: a genetic substudy from the STOPDAPT-2. Cardiovasc. Interv. Ther. 36, 403–415 (2021).

    Article  CAS  PubMed  Google Scholar 

  89. Watanabe, H. et al. Comparison of clopidogrel monotherapy after 1 to 2 months of dual antiplatelet therapy with 12 months of dual antiplatelet therapy in patients with acute coronary syndrome. JAMA Cardiol. 7, 407–417 (2022).

    Article  PubMed  Google Scholar 

  90. O’Donoghue, M. L., Murphy, S. A. & Sabatine, M. S. The safety and efficacy of aspirin discontinuation on a background of a P2Y12 inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation 142, 538–545 (2020).

    Article  PubMed  Google Scholar 

  91. Giacoppo, D. et al. Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials. Eur. Heart J. 42, 308–319 (2021).

    Article  CAS  PubMed  Google Scholar 

  92. Zhao, Q. et al. Effect of ticagrelor plus aspirin, ticagrelor alone, or aspirin alone on saphenous vein graft patency 1 year after coronary artery bypass grafting: a randomized clinical trial. JAMA 319, 1677–1686 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Valgimigli, M. et al. P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials. BMJ 373, n1332 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  94. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03234114 (2022).

  95. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03431142 (2020).

  96. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03119012 (2022).

  97. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04570345 (2020).

  98. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03971500 (2021).

  99. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04937699 (2021).

  100. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04753749 (2022).

  101. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04360720 (2022).

  102. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04609111 (2022).

  103. Kogame, N. et al. Prasugrel monotherapy after PCI with the SYNERGY stent in patients with chronic stable angina or stabilized acute coronary syndromes: rationale and design of the ASET pilot study. EuroIntervention 15, e547–e550 (2019).

    Article  PubMed  Google Scholar 

  104. Kogame, N. et al. Aspirin-free prasugrel monotherapy following coronary artery stenting in patients with stable CAD. JACC Cardiovasc. Interv. 13, 2251–2262 (2020).

    Article  PubMed  Google Scholar 

  105. Lopes, R. D. et al. Safety and efficacy of antithrombotic strategies in patients with atrial fibrillation undergoing percutaneous coronary intervention: a network meta-analysis of randomized controlled trials. JAMA Cardiol. 4, 747–755 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Capodanno, D. 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 Assoc. 9, e017212 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gargiulo, G. 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, 3757–3767 (2019).

    Article  CAS  PubMed  Google Scholar 

  108. Capodanno, D. et al. Management of antithrombotic therapy in atrial fibrillation patients undergoing PCI. J. Am. Coll. Cardiol. 74, 83–99 (2019).

    Article  PubMed  Google Scholar 

  109. Hindricks, G. et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur. Heart J. 42, 373–498 (2021).

    Article  PubMed  Google Scholar 

  110. Angiolillo, D. J. et al. Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention. Circulation 143, 583–596 (2021).

    Article  CAS  PubMed  Google Scholar 

  111. January, C. T. et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Rhythm Society in Collaboration with the Society of Thoracic Surgeons. Circulation 140, e125–e151 (2019).

    Article  PubMed  Google Scholar 

  112. Kirchhof, P. et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with the EACTS. Eur. Heart J. 37, 2893–2962 (2016).

    Article  PubMed  Google Scholar 

  113. Steg, P. G. et al. Ticagrelor in patients with stable coronary disease and diabetes. N. Engl. J. Med. 381, 1309–1320 (2019).

    Article  CAS  PubMed  Google Scholar 

  114. Bhatt, D. L. et al. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial. Lancet 394, 1169–1180 (2019).

    Article  CAS  PubMed  Google Scholar 

  115. Eikelboom, J. W. et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N. Engl. J. Med. 377, 1319–1330 (2017).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cardio-Thoracic-Vascular and Transplant Department, Azienda Ospedaliero-Universitaria Policlinico “Gaspare Rodolico – San Marco”, University of Catania, Catania, Italy

    Davide Capodanno

  2. University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Usman Baber

  3. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Deepak L. Bhatt

  4. ACTION Group, Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Institut de Cardiologie, Paris, France

    Jean-Philippe Collet

  5. Icahn School of Medicine at Mount Sinai, Cardiovascular Institute, New York, NY, USA

    George Dangas & Roxana Mehran

  6. University of Florida College of Medicine, Jacksonville, FL, USA

    Francesco Franchi, Fabiana Rollini & Dominick J. Angiolillo

  7. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    C. Michael Gibson

  8. Department of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Hyeon-Cheol Gwon

  9. Deutsches Herzzentrum München, Cardiology and Technische Universität München, Munich, Germany

    Adnan Kastrati

  10. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Takeshi Kimura & Hirotoshi Watanabe

  11. Hospital Israelita Albert Einstein and Heart Institute (InCor) University of São Paulo Medical School, São Paulo, Brazil

    Pedro A. Lemos

  12. Duke University Medical Center, The Duke Clinical Research Institute, Durham, NC, USA

    Renato D. Lopes & Sunil V. Rao

  13. TIMI Study Group, Brigham and Women’s Hospital, Boston, MA, USA

    Michelle L. O’Donoghue

  14. The Lambe Institute for Translational Medicine and Curam, National University of Ireland Galway, Galway, Ireland

    Patrick W. Serruys

  15. Université de Paris, INSERM U-1148, AP-HP, Hôpital Bichat, Paris, France

    Philippe G. Steg

  16. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK

    Robert F. Storey

  17. Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano and Bern University Hospital, Bern, Switzerland

    Marco Valgimigli

  18. Department of Cardiology and Critical Care Medicine, Jessaziekenhuis, Faculty of Medicine and Life Sciences, University of Hasselt, Hasselt, Belgium

    Pascal Vranckx

  19. Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland

    Stephan Windecker

Authors
  1. Davide Capodanno
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  2. Usman Baber
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  3. Deepak L. Bhatt
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  4. Jean-Philippe Collet
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  9. Adnan Kastrati
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  10. Takeshi Kimura
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  13. Roxana Mehran
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  14. Michelle L. O’Donoghue
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  15. Sunil V. Rao
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  16. Fabiana Rollini
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  18. Philippe G. Steg
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  22. Hirotoshi Watanabe
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  24. Dominick J. Angiolillo
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Contributions

D.C. and D.J.A. researched data for the article, discussed its content and wrote the manuscript. All the authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Dominick J. Angiolillo.

Ethics declarations

Competing interests

D.C. reports personal fees from Amgen, Arena, Biotronik, Daiichi Sankyo, Sanofi and Terumo; and consulting fees paid to the institution from Medtronic. U.B. reports personal fees from Amgen and AstraZeneca. D.L.B. discloses the following relationships — Advisory Board: Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Boston VA Research Institute, DRS.LINQ (stock options), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, AHA Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, Rutgers University (for the NIH-funded MINT trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, Svelte; Trustee: ACC; Unfunded Research: FlowCo, Merck, Takeda. J.-P.C. declares honoraria from Amgen, AstraZeneca, BMS/Pfizer, Chiesi and Webmed; and academic research grants from BMS/Pfizer and Medtronic. F.F. declares that he has received payment as an individual for consulting fee or honoraria from AstraZeneca, Bayer and Sanofi; and institutional payments for grants from PLx Pharma and The Scott R. MacKenzie Foundation. C.M.G. receives research support from Johnson & Johnson; and consulting support from AstraZeneca, Janssen & Bayer and Johnson & Johnson. H.-C.G. reports research grants from Abbott Vascular Korea, Boston Scientific Korea and Edwards Lifesciences. T.K. reports research funding from Abbott Medical and Boston Scientific. P.A.L. reports institutional research funding, and/or unpaid advisory board member, and/or unpaid member of the steering/executive/data safety and monitoring group of trials, and/or unpaid interventional proctor, by Abbott, Boston Scientific, Corindus, Flouit and Scietch, but has not received personal payments from pharmaceutical companies or device manufacturers; and being part of Argonauts, an innovation facilitator; and being partially supported by a grant from The National Council for Scientific and Technological Development (CNPq)–Brazil (grant number 306677/2019-9). R.D.L. reports research support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic and Pfizer; and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer and Portola. R.M. reports institutional research payments from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Applied Therapeutics, Arena, AstraZeneca, BAIM, Bayer, Beth Israel Deaconess, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CellAegis, CeloNova, CERC, Chiesi, Concept Medical, CSL Behring, Cytosorbents, DSI, Duke University, Element Science, Faraday, Humacyte, Idorsia, Insel Gruppe AG, Magenta, Medtronic, Novartis, OrbusNeich, Philips, RenalPro, Vivasure and Zoll; personal fees from Cine-Med Research and WebMD; consulting fees paid to the institution from Abbott, Janssen, Medtronic and Novartis; equity <1% in Applied Therapeutics, Elixir Medical, STEL and CONTROLRAD (spouse); Scientific Advisory Board for AMA, ACC (BOT Member) and SCAI (Women in Innovations Committee Member); and Faculty for CRF (no fee). M.L.O.’D. has received grants via Brigham and Women’s Hospital from Amgen, AstraZeneca, Intarcia, Janssen, Merck, Novartis and Pfizer; and honoraria from Amgen, AstraZeneca, Janssen and Novartis. S.V.R. reports institutional research funding from the ACC, Bayer and the National Heart, Lung, and Blood Institute. P.W.S. reports consultancy payments from Merillife, Novartis, Philips, SMT and Xeltic. P.G.S. reports receiving research grants from Amarin, Bayer, Sanofi and Servier; compensation for work on clinical trials (steering committee, clinical events committee or data safety and monitoring board) from Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi and Servier; and for consulting or speaking from Amarin, Amgen, BMS/Myokardia, Merck, Novo-Nordisk and Regeneron; and being a Senior Associate Editor at Circulation. R.F.S. reports research grants from AstraZeneca, Cytosorbents, Glycardial Diagnostics and Thromboserin; personal fees from Alnylam, Bayer, Bristol-Myers Squibb/Pfizer, CSL Behring, Cytosorbents, Glycardial Diagnostics, Hengrui, Idorsia, Intas Pharmaceuticals, Novartis, PhaseBio, Portola, Sanofi Aventis and Thromboserin. M.V. reports grants and personal fees from Terumo, and personal fees from Abbott Vascular, Alvimedica/CID, AstraZeneca, Bayer, Biotronik, Boston Scientific, Bristol-Myers Squibb, Chiesi, CoreFLOW, Daiichi Sankyo, Idorsia Pharmaceuticals, Medtronic, Novartis, PhaseBio, Universität Basel (Department of Klinische Forschung), Vesalio and Vifor. P.V. reports personal fees from Bayer, Daiichi-Sankyo, CSL Behring and Novartis. H.W. reports receiving personal fees from Abbott and Daiichi-Sankyo. S.W. reports research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Bayer, Biotronik, BMS, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Sinomed, Terumo and V-Wave; he also serves as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, BMS, Boston Scientific, Cardiovalve, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave and Xeltis, but has not received personal payments from pharmaceutical companies or device manufacturers; he is also member of the steering/executive committee group of several investigator-initiated trials that receive funding from industry without affecting his personal remuneration. D.J.A. has received payment as an individual for consulting fee or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Pfizer, PhaseBio, PLx Pharma and Sanofi; institutional payments for grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli-Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions and the Scott R. MacKenzie Foundation. The other authors declare no competing interests.

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Capodanno, D., Baber, U., Bhatt, D.L. et al. P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention. Nat Rev Cardiol 19, 829–844 (2022). https://doi.org/10.1038/s41569-022-00725-6

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