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.

Abstract

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 A2 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.

• Authors: Thomas W Johnson, Sarah Baos, Laura Collett, James L Hutchinson, Martin Nkau, Maria Molina, Riyaad Aungraheeta, Christopher Reilly-Stitt, Ruth Bowles, Barnaby C Reeves, Chris A Rogers, Stuart J Mundell, Andreas Baumbach, Andrew D Mumford
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 9 Issue 24 Pg. e016495 (12 15 2020) ISSN: 2047-9980 [Electronic] England
• PMID: 33305660 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Peptide Fragments
• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Receptors, Thromboxane A2, Prostaglandin H2
• thrombin receptor peptide (42-47)
• Arachidonic Acid
• Ticagrelor
• Aspirin

Topics

• Acute Coronary Syndrome (blood, drug therapy)
• Aged
• Arachidonic Acid (blood)
• Aspirin (therapeutic use)
• Drug Therapy, Combination (adverse effects, methods)
• Dual Anti-Platelet Therapy (adverse effects, methods)
• Female
• Humans
• Male
• Middle Aged
• Peptide Fragments (drug effects)
• Percutaneous Coronary Intervention (adverse effects)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (therapeutic use)
• Platelet Function Tests (methods)
• Purinergic P2Y Receptor Antagonists (administration & dosage, pharmacology, therapeutic use)
• Receptors, Thromboxane A2, Prostaglandin H2 (agonists)
• Ticagrelor (administration & dosage, pharmacology, therapeutic use)