Effect of Alternative Administrations on P2Y12 Receptor Inhibitors’ Pharmacokinetics and Pharmacodynamics: Systematic Review and Meta-Analysis

Valgimigli M, Bueno H, Byrne RA, Collet J-P, Costa F, Jeppsson A, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2018;39:213–60.

Article  PubMed  Google Scholar 

Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Invest. 2004;113:340–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Floyd CN, Passacquale G, Ferro A. Comparative Pharmacokinetics and Pharmacodynamics of Platelet Adenosine Diphosphate Receptor Antagonists and their Clinical Implications. Clinical Pharmacokinetics. 2012;51:429–42.

Article  CAS  PubMed  Google Scholar 

Gelbenegger G, Jilma B. Clinical pharmacology of antiplatelet drugs. Expert Rev Clin Pharmacol. 2022;15:1177–97.

Article  CAS  PubMed  Google Scholar 

Jourdi G, Lordkipanidzé M, Philippe A, Bachelot-Loza C, Gaussem P. Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases. Int J Mol Sci. 2021;22:13079.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heestermans AACM, van Werkum JW, Taubert D, Seesing TH, von Beckerath N, Hackeng CM, et al. Impaired bioavailability of clopidogrel in patients with a ST-segment elevation myocardial infarction. Thromb Res. 2008;122:776–81.

Article  CAS  PubMed  Google Scholar 

Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, et al. Response Variability to P2Y12 Receptor Inhibitors. JACC: Cardiovasc Interv. 2013;6:1111–28.

PubMed  Google Scholar 

Konecki C, Holm M, Djerada Z. Negative impact of ST-segment elevation myocardial infarction and morphine dose on ticagrelor uptake and pharmacodynamics: A population PK/PD analysis of pooled individual participant data. Clin Pharmacokinet. 2023;62:905–20.

Article  CAS  PubMed  Google Scholar 

Adamski P, Buszko K, Sikora J, Niezgoda P, Fabiszak T, Ostrowska M, et al. Determinants of high platelet reactivity in patients with acute coronary syndromes treated with ticagrelor. Sci Rep. 2019;9:3924.

Article  PubMed  PubMed Central  Google Scholar 

Rollini F, Franchi F, Hu J, Kureti M, Aggarwal N, Durairaj A, et al. Crushed prasugrel tablets in patients With STEMI undergoing primary percutaneous coronary intervention. J Am Coll Cardiol. 2016;67:1994–2004.

Article  CAS  PubMed  Google Scholar 

Asher E, Frydman S, Katz M, Regev E, Sabbag A, Mazin I, et al. Chewing versus swallowing ticagrelor to accelerate platelet inhibition in acute coronary syndrome - the CHEERS study: For The PLATIS (Platelets and Thrombosis in Sheba) study group. Thromb Haemost. 2017;117:727–33.

Article  PubMed  Google Scholar 

Parodi G, Xanthopoulou I, Bellandi B, Gkizas V, Valenti R, Karanikas S, et al. Ticagrelor crushed tablets administration in STEMI patients. J Am Coll Cardiol. 2015;65:511–2.

Article  PubMed  Google Scholar 

Gargiulo G, Esposito G, Avvedimento M, Nagler M, Minuz P, Campo G, et al. Cangrelor, tirofiban, and chewed or standard prasugrel regimens in patients with ST-Segment–Elevation Myocardial Infarction: Primary Results of the FABOLUS-FASTER Trial. Circulation. 2020;142:441–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Perla HT, Thomson VS, Attumalil TV, Geevar T, Alex AG, Dave RG, et al. Randomized, double-blind, active comparator pharmacodynamic study of platelet inhibition with crushed and integral formulations of clopidogrel and ticagrelor in acute coronary syndrome. Am J Cardiovasc Drugs. 2023;23:455–66.

Article  CAS  PubMed  Google Scholar 

Niezgoda P, Sikora J, Barańska M, Sikora A, Buszko K, Siemińska E, et al. Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina: A pharmacokinetic/pharmacodynamic study. Thromb Haemost. 2017;117:718–26.

Article  PubMed  Google Scholar 

Venetsanos D, Sederholm Lawesson S, Swahn E, Alfredsson J. Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets. Thromb Res. 2017;149:88–94.

Article  CAS  PubMed  Google Scholar 

Serenelli M, Pavasini R, Vitali F, Tonet E, Bilotta F, Parodi G, et al. Efficacy and safety of alternative oral administrations of P2Y12-receptor inhibitors: Systematic review and meta-analysis. J Thromb Haemost. 2019;17:944–50.

Article  CAS  PubMed  Google Scholar 

Haghbayan H, Deif B, Coomes EA. Chewed or crushed administration of adenosine diphosphate receptor inhibitors in acute coronary syndromes: a systematic review and meta-analysis of randomized controlled trials. Cardiovasc Drugs Ther. 2020;34:139–42.

Article  CAS  PubMed  Google Scholar 

Guo C, Zhao J-R, Chen M-J, Zhang Y, Wu R-Y, Li Q-Q, et al. Crushed/chewed administration of potent P2Y 12 inhibitors in ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: Systematic review and meta-analysis. Platelets. 2022;33:679–86.

Article  CAS  PubMed  Google Scholar 

Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928–d5928.

Article  PubMed  PubMed Central  Google Scholar 

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898.

Article  PubMed  Google Scholar 

Pick JL, Nakagawa S, Noble DWA. Reproducible, flexible and high-throughput data extraction from primary literature: The metaDigitise R package [Internet]. Evolutionary Biology; 2018 Jan. Available from: http://biorxiv.org/lookup/doi/https://doi.org/10.1101/247775

Viechtbauer W. Conducting Meta-Analyses in R with the metafor Package. J Stat Soft [Internet]. 2010 [cited 2024 Oct 7];36. Available from: http://www.jstatsoft.org/v36/i03/

Tralongo F, Konecki C, Feliu C, Kaladjian A, Djerada Z. Association Between Clozapine Plasma Concentrations and Treatment Response: A Systematic Review, Meta-analysis and Individual Participant Data Meta-analysis. Clin Pharmacokinet. 2023;62:807–18.

Article  CAS  PubMed  Google Scholar 

Hadjoudj J, Konecki C, Feliu C, Djerada Z. Association between olanzapine plasma concentrations and treatment response: A systematic review, meta-analysis and individual participant data meta-analysis. Biomed Pharmacother. 2024;172: 116236.

Article  CAS  PubMed  Google Scholar 

Alexopoulos D, Barampoutis N, Gkizas V, Vogiatzi C, Tsigkas G, Koutsogiannis N, et al. Crushed versus integral tablets of ticagrelor in st-segment elevation myocardial infarction patients: a randomized pharmacokinetic/Pharmacodynamic Study. Clin Pharmacokinet. 2016;55:359–67.

Article  CAS  PubMed  Google Scholar 

Asher E, Tal S, Mazin I, Abu-Much A, Sabbag A, Katz M, et al. Effect of chewing vs swallowing ticagrelor on platelet inhibition in patients with ST-segment elevation myocardial infarction: a randomized clinical trial. JAMA Cardiol. 2017;2:1380.

Article  PubMed  PubMed Central  Google Scholar 

Wilson TF, Ashraf M, Jan MF, Nfor T, Kostopoulos L, Solis J, et al. Chewed Versus Swallowed Ticagrelor in P2Y12 Inhibitor-Naïve Patients Undergoing Percutaneous Coronary Intervention. J Patient-Centered Res Rev. 2023;10:50–7.

Article  Google Scholar 

Vlachojannis GJ, Wilschut JM, Vogel RF, Lemmert ME, Delewi R, Diletti R, et al. Effect of prehospital crushed prasugrel tablets in patients With ST-segment–elevation myocardial infarction planned for primary percutaneous coronary intervention: The Randomized COMPARE CRUSH Trial. Circulation. 2020;142:2316–28.

Article  CAS  PubMed  Google Scholar 

Vogel RF, Delewi R, Angiolillo DJ, Wilschut JM, Lemmert ME, Diletti R, et al. Pharmacodynamic effects of pre-hospital administered crushed prasugrel in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2021;14:1323–33.

Article  PubMed  Google Scholar 

Greulich S, Mayr A, Gloekler S, Seitz A, Birkmeier S, Schäufele T, et al. Time-dependent myocardial necrosis in patients with ST-segment-elevation myocardial infarction without angiographic collateral flow visualized by cardiac magnetic resonance imaging: results from the multicenter STEMI-SCAR project. J Am Heart Assoc. 2019;8: e012429.

Article  PubMed  PubMed Central  Google Scholar 

Zafar MU, Farkouh ME, Fuster V, Chesebro JH. Crushed clopidogrel administered via nasogastric tube has faster and greater absorption than oral whole tablets. J Interv Cardiol. 2009;22:385–9.

Article  PubMed 

Comments (0)

No login
gif