Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 4/2023

17.02.2022 | Original Article

Dual Antiplatelet Therapy with 3rd Generation P2Y12 Inhibitors in STEMI Patients: Impact of Body Mass Index on Loading Dose–Response

verfasst von: Fernando Scudiero, Mario E. Canonico, Giuseppe D. Sanna, Filippo Dossi, Angelo Silverio, Gennaro Galasso, Giovanni Esposito, Italo Porto, Guido Parodi

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 4/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose

This study aims to assess the association between body mass index (BMI) and platelet reactivity in STEMI patients treated with oral 3rd generation P2Y12 inhibitors.

Methods

Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to BMI (BMI < 25 vs ≥ 25 kg/m2). A propensity score matching (1:1) was performed to balance potential confounders in patient baseline characteristics. Platelet reactivity was assessed by VerifyNow at baseline and after 3rd generation P2Y12 inhibitor (ticagrelor or prasugrel) loading dose (LD). Blood samples were obtained at baseline (T0), 1 h (T1), 2 h (T2), 4–6 h (T3), and 8–12 h (T4) after the LD. High on-treatment platelet reactivity (HTPR) was defined as a platelet reactivity unit value ≥ 208 units.

Results

After propensity score matching, patients with BMI ≥ 25 had similar values of baseline platelet reactivity, while they had higher level of platelet reactivity at 1 and 2 h after the LD and higher rate of HRPT. Furthermore, multivariate analysis demonstrated that BMI ≥ 25 was an independent predictor of HTPR at 2 h (OR 2.01, p = .009). Conversely, starting from 4 h after the LD, platelet reactivity values and HRPT rates were comparable among the two study groups.

Conclusions

A BMI ≥ 25 kg/m2 is associated with delayed pharmacodynamic response to oral 3rd generation P2Y12 inhibitor LD, and it is a strong predictor of HTPR in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018;39(3):213–60.CrossRefPubMed Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018;39(3):213–60.CrossRefPubMed
2.
Zurück zum Zitat 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. 2018;39(2):119–77.CrossRefPubMed 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. 2018;39(2):119–77.CrossRefPubMed
3.
Zurück zum Zitat van der Sangen NMR, Rozemeijer R, Chan P, Yin DRPP, et al. Patient-tailored antithrombotic therapy following percutaneous coronary intervention. Eur Heart J. 2021;42(10):1038–46.CrossRefPubMedPubMedCentral van der Sangen NMR, Rozemeijer R, Chan P, Yin DRPP, et al. Patient-tailored antithrombotic therapy following percutaneous coronary intervention. Eur Heart J. 2021;42(10):1038–46.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Parodi G, Marcucci R, Valenti R, et al. High on treatment platelet reactivity after clopidogrel loading and long-term cardiovascu- lar events among patients with acute coronary syndromes undergoing PCI. JAMA. 2011;306:1215–23.CrossRefPubMed Parodi G, Marcucci R, Valenti R, et al. High on treatment platelet reactivity after clopidogrel loading and long-term cardiovascu- lar events among patients with acute coronary syndromes undergoing PCI. JAMA. 2011;306:1215–23.CrossRefPubMed
5.
Zurück zum Zitat Scudiero F, Zocchi C, De Vito E, et al. Relationship between CHA2DS2-VASc score, coronary artery disease severity, residual platelet reactivity and long-term clinical outcomes in patients with acute coronary syndrome. Int J Cardiol. 2018;262:9–13.CrossRefPubMed Scudiero F, Zocchi C, De Vito E, et al. Relationship between CHA2DS2-VASc score, coronary artery disease severity, residual platelet reactivity and long-term clinical outcomes in patients with acute coronary syndrome. Int J Cardiol. 2018;262:9–13.CrossRefPubMed
6.
Zurück zum Zitat Mourikis P, Zako S, Dannenberg L, et al. Aspirin antiplatelet effects are associated with body weight. Vascul Pharmacol. 2020;125–126:106635.CrossRefPubMed Mourikis P, Zako S, Dannenberg L, et al. Aspirin antiplatelet effects are associated with body weight. Vascul Pharmacol. 2020;125–126:106635.CrossRefPubMed
8.
Zurück zum Zitat Parodi G, Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol. 2013;61(15):1601–6.CrossRefPubMed Parodi G, Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol. 2013;61(15):1601–6.CrossRefPubMed
9.
Zurück zum Zitat Parodi G, Bellandi B, Valenti R, et al. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study. Am Heart J. 2014;167(6):909–14.CrossRefPubMed Parodi G, Bellandi B, Valenti R, et al. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study. Am Heart J. 2014;167(6):909–14.CrossRefPubMed
10.
Zurück zum Zitat Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor crushed tablets administration in STEMI patients: the MOJITO study. J Am Coll Cardiol. 2015;65(5):511–2.CrossRefPubMed Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor crushed tablets administration in STEMI patients: the MOJITO study. J Am Coll Cardiol. 2015;65(5):511–2.CrossRefPubMed
11.
Zurück zum Zitat Parodi G, Talanas G, Mura E, et al. Orodispersible ticagrelor in acute coronary syndromes: the TASTER study. J Am Coll Cardiol. 2021;78(3):292–4.CrossRefPubMed Parodi G, Talanas G, Mura E, et al. Orodispersible ticagrelor in acute coronary syndromes: the TASTER study. J Am Coll Cardiol. 2021;78(3):292–4.CrossRefPubMed
12.
Zurück zum Zitat Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2021;143(21):e984–1010.CrossRefPubMedPubMedCentral Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2021;143(21):e984–1010.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Garcia-Garcia HM, McFadden EP, Farb A, et al. Academic Research Consortium. Standardized end point definitions for coronary intervention trials: the academic research consortium-2 consensus document. Circulation. 2018;137(24):2635–50.CrossRefPubMed Garcia-Garcia HM, McFadden EP, Farb A, et al. Academic Research Consortium. Standardized end point definitions for coronary intervention trials: the academic research consortium-2 consensus document. Circulation. 2018;137(24):2635–50.CrossRefPubMed
15.
16.
Zurück zum Zitat Burrai F, Sanna GD, Moccia E, et al. Beneficial effects of listening to classical music in patients with heart failure: a randomized controlled trial. J Card Fail. 2020;26(7):541–9.CrossRefPubMed Burrai F, Sanna GD, Moccia E, et al. Beneficial effects of listening to classical music in patients with heart failure: a randomized controlled trial. J Card Fail. 2020;26(7):541–9.CrossRefPubMed
17.
Zurück zum Zitat Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341(15):1097–105.CrossRefPubMed Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341(15):1097–105.CrossRefPubMed
18.
Zurück zum Zitat Bogers RP, Bemelmans WJ, Hoogenveen RT, et al. Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med. 2007;167(16):1720–8.CrossRefPubMed Bogers RP, Bemelmans WJ, Hoogenveen RT, et al. Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med. 2007;167(16):1720–8.CrossRefPubMed
20.
Zurück zum Zitat Scudiero F, Valenti R, Marcucci R, et al. Platelet reactivity in hepatitis C virus-infected patients on dual antiplatelet therapy for acute coronary syndrome. J Am Heart Assoc. 2020;9(18):e016441.CrossRefPubMedPubMedCentral Scudiero F, Valenti R, Marcucci R, et al. Platelet reactivity in hepatitis C virus-infected patients on dual antiplatelet therapy for acute coronary syndrome. J Am Heart Assoc. 2020;9(18):e016441.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Neergaard-Petersen S, Hvas AM, Kristensen SD, Grove EL. Platelets and antiplatelet therapy in patients with coronary artery disease and diabetes. Semin Thromb Hemost. 2016;42(3):234–41.CrossRefPubMed Neergaard-Petersen S, Hvas AM, Kristensen SD, Grove EL. Platelets and antiplatelet therapy in patients with coronary artery disease and diabetes. Semin Thromb Hemost. 2016;42(3):234–41.CrossRefPubMed
22.
Zurück zum Zitat Badimon L, Hernández Vera R, Padró T, Vilahur G. Antithrombotic therapy in obesity. Thromb Haemost. 2013;110:681–8.CrossRefPubMed Badimon L, Hernández Vera R, Padró T, Vilahur G. Antithrombotic therapy in obesity. Thromb Haemost. 2013;110:681–8.CrossRefPubMed
23.
Zurück zum Zitat Janson B, Thursky K. Dosing of antibiotics in obesity. Curr Opin Infect Dis. 2012;25:634–49.CrossRefPubMed Janson B, Thursky K. Dosing of antibiotics in obesity. Curr Opin Infect Dis. 2012;25:634–49.CrossRefPubMed
24.
Zurück zum Zitat Schilling U, Dingemanse J, Ufer M. Pharmacokinetics and pharmacodynamics of approved and investigational P2Y12 receptor antagonists. Clin Pharmacokinet. 2020;59(5):545–66.CrossRefPubMed Schilling U, Dingemanse J, Ufer M. Pharmacokinetics and pharmacodynamics of approved and investigational P2Y12 receptor antagonists. Clin Pharmacokinet. 2020;59(5):545–66.CrossRefPubMed
25.
Zurück zum Zitat Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment. J Clin Pharmacol. 2012;52:1388–98.CrossRefPubMed Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment. J Clin Pharmacol. 2012;52:1388–98.CrossRefPubMed
26.
Zurück zum Zitat Small DS, Wrishko RE, Ernest CS, Ni L, Winters KJ, Farid NA, et al. Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal impairment and end-stage renal disease. J Clin Pharm Ther. 2009;34:585–94.CrossRefPubMed Small DS, Wrishko RE, Ernest CS, Ni L, Winters KJ, Farid NA, et al. Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal impairment and end-stage renal disease. J Clin Pharm Ther. 2009;34:585–94.CrossRefPubMed
27.
Zurück zum Zitat Pankert M, Quilici J, Loundou AD, et al. Impact of obesity and the metabolic syndrome on response to clopidogrel or prasugrel and bleeding risk in patients treated after coronary stenting. Am J Cardiol. 2014;113(1):54–9.CrossRefPubMed Pankert M, Quilici J, Loundou AD, et al. Impact of obesity and the metabolic syndrome on response to clopidogrel or prasugrel and bleeding risk in patients treated after coronary stenting. Am J Cardiol. 2014;113(1):54–9.CrossRefPubMed
28.
Zurück zum Zitat Mayer K, Orban M, Bernlochner I, et al. Predictors of antiplatelet response to prasugrel during maintenance treatment. Platelets. 2015;26(1):53–8.CrossRefPubMed Mayer K, Orban M, Bernlochner I, et al. Predictors of antiplatelet response to prasugrel during maintenance treatment. Platelets. 2015;26(1):53–8.CrossRefPubMed
29.
Zurück zum Zitat Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.CrossRefPubMed Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.CrossRefPubMed
30.
Zurück zum Zitat Alexopoulos D, Xanthopoulou I, Storey RF, Bliden KP, Tantry US, Angiolillo DJ, Gurbel PA. Platelet reactivity during ticagrelor maintenance therapy: a patient-level data meta-analysis. Am Heart J. 2014;168(4):530–6.CrossRefPubMed Alexopoulos D, Xanthopoulou I, Storey RF, Bliden KP, Tantry US, Angiolillo DJ, Gurbel PA. Platelet reactivity during ticagrelor maintenance therapy: a patient-level data meta-analysis. Am Heart J. 2014;168(4):530–6.CrossRefPubMed
31.
Zurück zum Zitat Wells B, Gentry M, Ruiz-Arango A, Dias J, Landolfo CK. Relation between body mass index and clinical outcome in acute myocardial infarction. Am J Cardiol. 2006;98(4):474–7.CrossRefPubMed Wells B, Gentry M, Ruiz-Arango A, Dias J, Landolfo CK. Relation between body mass index and clinical outcome in acute myocardial infarction. Am J Cardiol. 2006;98(4):474–7.CrossRefPubMed
32.
Zurück zum Zitat Schüpke S, Neumann FJ, Menichelli M, ISAR-REACT 5 Trial Investigators, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019;381(16):1524–34.CrossRefPubMed Schüpke S, Neumann FJ, Menichelli M, ISAR-REACT 5 Trial Investigators, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019;381(16):1524–34.CrossRefPubMed
33.
Zurück zum Zitat Henrich A, Claussen CH, Dingemanse J, Krause A. Pharmacokinetic/pharmacodynamic modeling of drug interactions at the P2Y12 receptor between selatogrel and oral P2Y12 antagonists. CPT Pharmacometrics Syst Pharmacol. 2021;10(7):735–47.CrossRefPubMedPubMedCentral Henrich A, Claussen CH, Dingemanse J, Krause A. Pharmacokinetic/pharmacodynamic modeling of drug interactions at the P2Y12 receptor between selatogrel and oral P2Y12 antagonists. CPT Pharmacometrics Syst Pharmacol. 2021;10(7):735–47.CrossRefPubMedPubMedCentral
Metadaten
Titel
Dual Antiplatelet Therapy with 3rd Generation P2Y12 Inhibitors in STEMI Patients: Impact of Body Mass Index on Loading Dose–Response
verfasst von
Fernando Scudiero
Mario E. Canonico
Giuseppe D. Sanna
Filippo Dossi
Angelo Silverio
Gennaro Galasso
Giovanni Esposito
Italo Porto
Guido Parodi
Publikationsdatum
17.02.2022
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 4/2023
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-022-07322-2

Weitere Artikel der Ausgabe 4/2023

Cardiovascular Drugs and Therapy 4/2023 Zur Ausgabe

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.