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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

BACKGROUND: To assess differences in platelet inhibition during ticagrelor monotherapy (TIC) or dual therapy with ticagrelor and aspirin (TIC+ASP) in patients after percutaneous coronary intervention using a comprehensive panel of functional tests. METHODS AND RESULTS: In a single‐center parallel gr...

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Autores principales: Johnson, Thomas W., Baos, Sarah, Collett, Laura, Hutchinson, James L., Nkau, Martin, Molina, Maria, Aungraheeta, Riyaad, Reilly‐Stitt, Christopher, Bowles, Ruth, Reeves, Barnaby C., Rogers, Chris A., Mundell, Stuart J, Baumbach, Andreas, Mumford, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955396/
https://www.ncbi.nlm.nih.gov/pubmed/33305660
http://dx.doi.org/10.1161/JAHA.120.016495
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author Johnson, Thomas W.
Baos, Sarah
Collett, Laura
Hutchinson, James L.
Nkau, Martin
Molina, Maria
Aungraheeta, Riyaad
Reilly‐Stitt, Christopher
Bowles, Ruth
Reeves, Barnaby C.
Rogers, Chris A.
Mundell, Stuart J
Baumbach, Andreas
Mumford, Andrew D.
author_facet Johnson, Thomas W.
Baos, Sarah
Collett, Laura
Hutchinson, James L.
Nkau, Martin
Molina, Maria
Aungraheeta, Riyaad
Reilly‐Stitt, Christopher
Bowles, Ruth
Reeves, Barnaby C.
Rogers, Chris A.
Mundell, Stuart J
Baumbach, Andreas
Mumford, Andrew D.
author_sort Johnson, Thomas W.
collection PubMed
description BACKGROUND: To assess differences in platelet inhibition during ticagrelor monotherapy (TIC) or dual therapy with ticagrelor and aspirin (TIC+ASP) in patients after percutaneous coronary intervention using a comprehensive panel of functional tests. METHODS AND RESULTS: In a single‐center parallel group, open label, randomized controlled trial, 110 participants were randomized to receive either TIC (n=55) or TIC+ASP (n=55) for 4 weeks. The primary outcome was the platelet aggregation response with 10 μmol/L thrombin receptor activation peptide‐6 (TRAP‐6). The secondary outcomes were platelet aggregation responses and binding of surface activation markers with a panel of other activators. The mean percentage aggregation for 10 μmol/L TRAP‐6 was similar for the TIC and TIC+ASP groups (mean difference+4.29; 95% CI, −0.87 to +9.46). Aggregation was higher in the TIC group compared with the TIC+ASP group with 1 μg/mL (+6.47; +2.04 to +10.90) and 0.5 μg/mL (+14.00; +7.63 to +20.39) collagen related peptide. Aggregation responses with 5 μmol/L TRAP‐6, 5 μmol/L or 2.5 μmol/L thromboxane A(2) receptor agonist and surface activation marker binding with 5 μmol/L TRAP‐6 or 0.5 μg/mL collagen related peptide were the same between the treatment groups. CONCLUSIONS: Patients with PCI show similar levels of inhibition of most platelet activation pathways with TIC compared with dual therapy with TIC + ASP. However, the greater aggregation response with collagen related peptide during TIC indicates incomplete inhibition of glycoprotein VI (collagen) receptor‐mediated platelet activation. This difference in pharmacodynamic response to anti‐platelet medication may contribute to the lower bleeding rates observed with TIC compared with dual antiplatelet therapy in recent clinical trials. REGISTRATION INFORMATION: URL: https://www.isrctn.com; Unique Identifier ISRCTN84335288.
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spelling pubmed-79553962021-03-17 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 Johnson, Thomas W. Baos, Sarah Collett, Laura Hutchinson, James L. Nkau, Martin Molina, Maria Aungraheeta, Riyaad Reilly‐Stitt, Christopher Bowles, Ruth Reeves, Barnaby C. Rogers, Chris A. Mundell, Stuart J Baumbach, Andreas Mumford, Andrew D. J Am Heart Assoc Original Research BACKGROUND: To assess differences in platelet inhibition during ticagrelor monotherapy (TIC) or dual therapy with ticagrelor and aspirin (TIC+ASP) in patients after percutaneous coronary intervention using a comprehensive panel of functional tests. METHODS AND RESULTS: In a single‐center parallel group, open label, randomized controlled trial, 110 participants were randomized to receive either TIC (n=55) or TIC+ASP (n=55) for 4 weeks. The primary outcome was the platelet aggregation response with 10 μmol/L thrombin receptor activation peptide‐6 (TRAP‐6). The secondary outcomes were platelet aggregation responses and binding of surface activation markers with a panel of other activators. The mean percentage aggregation for 10 μmol/L TRAP‐6 was similar for the TIC and TIC+ASP groups (mean difference+4.29; 95% CI, −0.87 to +9.46). Aggregation was higher in the TIC group compared with the TIC+ASP group with 1 μg/mL (+6.47; +2.04 to +10.90) and 0.5 μg/mL (+14.00; +7.63 to +20.39) collagen related peptide. Aggregation responses with 5 μmol/L TRAP‐6, 5 μmol/L or 2.5 μmol/L thromboxane A(2) receptor agonist and surface activation marker binding with 5 μmol/L TRAP‐6 or 0.5 μg/mL collagen related peptide were the same between the treatment groups. CONCLUSIONS: Patients with PCI show similar levels of inhibition of most platelet activation pathways with TIC compared with dual therapy with TIC + ASP. However, the greater aggregation response with collagen related peptide during TIC indicates incomplete inhibition of glycoprotein VI (collagen) receptor‐mediated platelet activation. This difference in pharmacodynamic response to anti‐platelet medication may contribute to the lower bleeding rates observed with TIC compared with dual antiplatelet therapy in recent clinical trials. REGISTRATION INFORMATION: URL: https://www.isrctn.com; Unique Identifier ISRCTN84335288. John Wiley and Sons Inc. 2020-12-11 /pmc/articles/PMC7955396/ /pubmed/33305660 http://dx.doi.org/10.1161/JAHA.120.016495 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Johnson, Thomas W.
Baos, Sarah
Collett, Laura
Hutchinson, James L.
Nkau, Martin
Molina, Maria
Aungraheeta, Riyaad
Reilly‐Stitt, Christopher
Bowles, Ruth
Reeves, Barnaby C.
Rogers, Chris A.
Mundell, Stuart J
Baumbach, Andreas
Mumford, Andrew D.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955396/
https://www.ncbi.nlm.nih.gov/pubmed/33305660
http://dx.doi.org/10.1161/JAHA.120.016495
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