{"doi":"10.1016/j.vph.2023.107143","title":"Ticagrelor inhibits platelet aggregation and reduces inflammatory burden more than clopidogrel in patients with stages 4 or 5 chronic kidney disease","abstract":"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).","journal":"Vascular Pharmacology","year":2023,"id":357561,"datarank":0.561029565869168,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.1762871622499374,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.1762871622499374,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":10,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03649711"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295117,"name":"Adam Corken","orcid":"0000-0002-4700-9091","position":1,"is_corresponding":false},{"id":245938,"name":"John M. Arthur","orcid":"0000-0003-4342-4762","position":2,"is_corresponding":false},{"id":295118,"name":"Jerry Ware","orcid":"0000-0001-8860-6338","position":3,"is_corresponding":false},{"id":1107360,"name":"Narenraj Arulprakash","orcid":"0000-0002-3493-7868","position":4,"is_corresponding":false},{"id":529899,"name":"Junqiang Dai","orcid":"0000-0002-5626-0114","position":5,"is_corresponding":false},{"id":436567,"name":"Milind A. Phadnis","orcid":"0000-0001-6472-9325","position":6,"is_corresponding":false},{"id":1107361,"name":"Otis M. Davis","orcid":"0009-0008-2731-9018","position":7,"is_corresponding":false},{"id":511516,"name":"Yasir Rahmatallah","orcid":"0000-0002-8176-6328","position":8,"is_corresponding":false},{"id":1107851,"name":"J. L. Mehta","orcid":null,"position":9,"is_corresponding":false},{"id":387446,"name":"S. Susan Hedayati","orcid":"0000-0001-8850-4729","position":10,"is_corresponding":false},{"id":748408,"name":"Susan S. Smyth","orcid":"0000-0001-6840-7892","position":11,"is_corresponding":false},{"id":666430,"name":"Nishank Jain","orcid":"0000-0001-6356-6579","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"36682595","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}