Abstract: SA-PO917
Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Aggregation in Patients With Stages 4-5 CKD
Session Information
- CKD: Clinical Trials and Pharmacoepidemiology
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials
Authors
- Davis, Otis, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
- Dai, Junqiang, University of Kansas School of Medicine, Kansas City, Kansas, United States
- Jain, Nishank, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
Background
Although the more potent ticagrelor was shown to be superior to clopidogrel in reducing thrombotic events and mortality in a subgroup of PLATO trial non-dialysis participants with stage 4-5 CKD, post-marketing studies failed to demonstrate similar benefits among CKD population. Studies exploring the antiplatelet effects of ticagrelor in CKD have been limited by the lack of a control arm, high drop-out rates and lack of randomization. There are no RCT to dissect antiplatelet effects of ticagrelor vs. clopidogrel in CKD.
Methods
We conducted a mechanistic, double-blind, RCT to compare ADP-induced platelet aggregation on treatment with ticagrelor vs. clopidogrel in 48 people with CKD. In a parallel arm, we investigated the pharmacokinetics and the antiplatelet effects of ticagrelor among CKD and non-CKD controls (n=26).
Results
The population of our study was diverse- mean age 53.7 years, 62% women, 54% African American, mean GFR 16 ml/min/1.73m2. Ticagrelor was found to be statistically superior to clopidogrel at inhibiting ADP-induced WBPA (87 ± 22% vs. 63 ± 50% inhibition of platelet aggregation; P=0.04), while the difference in post-treatment values remained significant when adjusting for diabetes (ANCOVA P=0.002). There were no differences in the percent inhibition of ADP-induced platelet aggregation between CKD (87 ± 22%) and controls (77 ±29%), P=0.14. This coincided with no difference in the pharmacokinetics of ticagrelor and its metabolite between CKD and controls.
Conclusion
Our findings provide mechanistic evidence for the greater efficacy of ticagrelor over clopidogrel in patients with stage 4-5 CKD.
Graphs showing asprin effect and P2Y12 inhibitor effect
Peak and trough plasma levels of ticagelor and its active metabolite
Funding
- Private Foundation Support