Personalized antiplatelet therapy in a post-PCI patient with high bleeding risk

Background: Therapeutic de-escalation involving P2Y12 receptor inhibitors, such as transitioning from prasugrel or ticagrelor to clopidogrel or reducing the dose of prasugrel or ticagrelor, has been proposed as an alternative strategy for dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS). This approach is particularly relevant for patients at high bleeding risk who are unsuitable for potent P2Y12 receptor inhibitors. However, de-escalation within the first 30 days following the ACS index event is associated with an increased risk of ischemic events and is generally not recommended. Case: We present a clinical case of a post-percutaneous coronary intervention (PCI) patient with a high risk of bleeding who underwent de-escalation of DAPT. The approach involved reducing the dose of ticagrelor, a potent P2Y12 receptor inhibitor, guided by platelet function testing and genetic analysis. A transition to clopidogrel, a less potent P2Y12 receptor inhibitor, was not feasible due to prior stent thrombosis while the patient was on clopidogrel. Conclusions: This case highlights the importance of individualized antithrombotic strategies in high-risk patients. Prospective evaluation of de-escalation strategies using platelet function testing or genetic analysis is recommended to optimize therapy while minimizing both bleeding and ischemic risks.

Percutaneous coronary intervention; P2Y12 receptor inhibitor; Residual platelet reactivity; Bleeding; De-escalation

[1] Sawayama Y, Yamaji K, Kohsaka S, Yamamoto T, Higo Y, Numasawa Y, et al. Variation in in-hospital mortality and its association with percutaneous coronary intervention-related bleeding complications: a report from nationwide registry in Japan. PLOS ONE. 2021; 16: e0261371.

[2] Sibbing D, Aradi D, Alexopoulos D, ten Berg J, Bhatt DL, Bonello L, et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC: Cardiovascular Interventions. 2019; 12: 1521–1237.

[3] Park DW, Kwon O, Jang JS, Yun SC, Park H, Kang DY, et al. Clinically significant bleeding with ticagrelor versus clopidogrel in korean patients with acute coronary syndromes intended for invasive management: a randomized clinical trial. Circulation. 2019; 140: 1865–1877.

[4] Jeong Y, Tantry US, Omar M, Navarese E, Gorog DA, Gurbel PA. “East Asian Paradox” revisited: precision medicine for antithrombotic strategies tailored to atherothrombotic cardiovascular risks. Journal of Cardiovascular Intervention. 2024; 3: 119–135.

[5] Small DS, Kothare P, Yuen E, Lachno DR, Li YG, Winters KJ, et al. The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese, and Korean subjects compared with healthy Caucasian subjects. European Journal of Clinical Pharmacology. 2010; 66: 127–135.

[6] Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. European Heart Journal. 2018; 39: 213–260.

[7] Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. European Heart Journal. 2019; 40: 87–165.

[8] Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, 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. The Lancet. 2017; 390: 1747–1757.

[9] Collet JP, Thiele H, Barbato E, Bauersachs J, Dendale P, Edvardsen T, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal. 2021; 42: 1289–1367.

[10] Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. European Heart Journal. 2023; 44: 3720–3826.

[11] Mansurova JA, Karazhanova LK. Independent predictors of adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention during hospitalization. Kardiologiya. 2018; 58: 22–29.

[12] Kim MH, Choi SY, An SY, Serebruany V. Validation of three platelet function tests for bleeding risk stratification during dual antiplatelet therapy following coronary interventions. Clinical Cardiology. 2016; 39: 385–390.

[13] Puchinian NF, Furman NV, Malinova LI, Dolotovskaya PV. Monitoring of the effectiveness of antiplatelet therapy in cardiology practice. Rational Pharmacotherapy in Cardiology. 2017; 13: 107–115.

[14] Jin CD, Kim MH, Bang J, Serebruany V. A prospective, randomized, open-label, blinded, endpoint study exploring platelet response to half-dose prasugrel and ticagrelor in patients with the acute coronary syndrome: HOPE-TAILOR study. Cardiology. 2017; 138: 201–206.

[15] Jin CD, Kim MH, Song K, Jin X, Lee KM, Park JS, et al. Pharmacodynamics and outcomes of a de-escalation strategy with half-dose prasugrel or ticagrelor in east Asians patients with acute coronary syndrome: results from hope-tailor trial. Journal of Clinical Medicine. 2021; 10: 2699.

[16] Chen Q, Zhang Y, Wang Z, Wang S, Zhang H, Wang Y, et al. Efficacy and safety of low dose ticagrelor in patients with acute coronary syndrome: a systematic review and meta-analysis. Postgraduate Medical Journal. 2020; 96: 693–702.

[17] Tam CC, Tse HF. Antiplatelet therapy aims and strategies in Asian patients with acute coronary syndrome or stable coronary artery disease. Journal of Clinical Medicine. 2022; 11: 7440.