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 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.

Walking the Line with Ticagrelor: Meta-Analysis Comparing the Safety and Efficacy of Ticagrelor Monotherapy after a Short Course of Ticagrelor-Based Dual Antiplatelet Therapy versus Standard Therapy in Complex Percutaneous Coronary Intervention

“…The TEMPLATE (Ticagrelor Monotherapy and Platelet Reactivity) trial, a study investigating the pharmacodynamic differences between ticagrelor monotherapy versus ticagrelor and aspirin in patients after PCI, demonstrated similar levels of inhibition of most platelet activation pathways with ticagrelor compared with DAPT; however, a greater aggregation response was seen with a collagen activation marker, demonstrating an incomplete inhibition of glycoprotein VI (collagen) receptor-mediated platelet activation with ticagrelor alone as compared to DAPT. This difference in response can offer a pharmacodynamic explanation in the lower bleeding rates observed in our meta-analysis and recent trials [ 15 ]. However, the observed reduction in all-cause death may have more than one explanation and non-analyzed myocardial infarction in the TICO trial may have impacted on the mortality outcome.…”

P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention

“…In the presence of potent P2Y 12 blockade, in vitro pharmacodynamic investigations have shown that aspirin does not provide much additional antiplatelet effect [ 29 ]. This was also confirmed in a series of ex vivo pharmacodynamic studies [ 30 , 31 , 32 ]. While withdrawal of aspirin indeed eliminates its specific inhibitory effects mediated by the COX-1 pathway, other platelet signaling pathways are still affected by potent P2Y 12 blockade [ 20 , 33 ].…”

Comparative Efficacy and Safety of P2Y12 Inhibitor Monotherapy and Dual Antiplatelet Therapy in Patients with and without Diabetes Mellitus Undergoing Percutaneous Coronary Intervention

“…The success of P2Y12 inhibitor monotherapy was not a coincidence. Many in vitro and ex vivo investigations have shown that aspirin provided very limited additional platelet inhibition and anti-thrombotic effect to a potent P2Y12 inhibitor [28][29][30]. Of note, most of the patients treated with P2Y12 inhibitor monotherapy were using ticagrelor.…”