Ticagrelor inhibits platelet aggregation and reduces inflammatory burden more than clopidogrel in patients with stages 4 or 5 chronic kidney disease

Nishank Jain, Adam Corken, John M. Arthur, Jerry Ware, Narenraj Arulprakash, Junqiang Dai, Milind A. Phadnis, Otis Davis, Yasir Rahmatallah, J. L. Mehta, S. Susan Hedayati, Susan Smyth

Research output: Contribution to journalArticlepeer-review


Background: No study has compared pharmacologic properties of ticagrelor and clopidogrel in non-dialysis patients with stage 4–5 chronic kidney disease (CKD). Methods: We conducted a double-blind RCT to compare effects of ticagrelor and clopidogrel in 48 CKD, with the primary outcome of ADP-induced platelet aggregation (WBPA) after 2 weeks of DAPT. In a parallel arm, we compared effects of 2 weeks of ticagrelor plus aspirin on mean changes in WBPA and markers of thromboinflammation among non-CKD controls (n = 26) with that of CKD in the ticagrelor-arm. Results: Average age of CKD was 53.7 years, with 62% women, 54% African American, and 42% with stage 5 CKD. Ticagrelor generated statistically lower WBPA values post treatment [median 0 Ω (IQR 0, 2)] vs. clopidogrel [median 0 Ω (IQR 0, 5)] (P = 0.002); percent inhibition of WBPA was greater (87 ± 22% vs. 63 ± 50%; P = 0.04; and plasma IL-6 levels were much lower (8.42 ± 1.73 pg/ml vs. 18.48 ± 26.56 pg/ml; P = 0.04). No differences in mean changes in WBPA between CKD-ticagrelor and control groups were observed. Ticagrelor- DAPT reduced levels of IL-1α and IL-1β in CKD-ticagrelor and control groups, attenuated lowering of TNFα and TRAIL levels in CKD-ticagrelor (vs controls), and had global changes in correlation between various cytokines in a subgroup of CKD-ticagrelor subjects not on statins (n = 10). Peak/trough levels of ticagrelor/metabolite were not different between CKD-ticagrelor and control groups. Conclusions: We report significant differences in platelet aggregation and anti-inflammatory properties between ticagrelor- and clopidogrel-based DAPT in non-dialysis people with stage 4–5 CKD. These notable inflammatory responses suggest ticagrelor-based DAPT might lower inflammatory burden of asymptomatic patients with stage 4 or 5 CKD. (clinicaltrials.gov # NCT03649711).

Original languageEnglish (US)
Article number107143
JournalVascular Pharmacology
StatePublished - Feb 2023


  • Chronic kidney disease
  • Clopidogrel
  • Inflammation
  • Platelets
  • Ticagrelor

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology


Dive into the research topics of 'Ticagrelor inhibits platelet aggregation and reduces inflammatory burden more than clopidogrel in patients with stages 4 or 5 chronic kidney disease'. Together they form a unique fingerprint.

Cite this