{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:01:30Z","timestamp":1782295290269,"version":"3.54.5"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/01021-4"],"award-info":[{"award-number":["2014\/01021-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High platelet reactivity (HPR) in patients with coronary artery disease receiving P2Y12 inhibitors increases ischemic risk. Chronic kidney disease (CKD) is an established contributor to HPR during clopidogrel therapy. The objective of the study was to assess whether CKD influences platelet reactivity (PR) in patients treated with clopidogrel or ticagrelor. This double-blind, double-dummy study enrolled 106 stable patients more than one year after an acute coronary syndrome, with or without CKD. Participants were matched by age and sex and randomized to clopidogrel or ticagrelor. PR was measured using the VerifyNow\u2122 P2Y12 assay, and HPR was defined as P2Y12 reaction units (PRU) \u2265 208. Median glomerular filtration rates were 80 mL\/min\/1.73 m2 in non-CKD patients and 41 mL\/min\/1.73 m2 in CKD patients (p &lt; 0.01). Ticagrelor produced similarly low PR in both groups (36 vs. 35 PRU; p = 0.61). Clopidogrel resulted in a numerically higher PR in CKD patients (209 vs. 180 PRU; p = 0.07). The magnitude of PR reduction with ticagrelor relative to clopidogrel was greater in CKD patients (p-interaction = 0.09). HPR was markedly more common with clopidogrel, particularly in CKD (difference 37%; adjusted OR 4.42; p = 0.01). In conclusion, CKD significantly impairs clopidogrel responsiveness but does not affect ticagrelor, resulting in a greater relative advantage of ticagrelor in patients with CKD.<\/jats:p>","DOI":"10.3390\/ijms27031359","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T14:52:36Z","timestamp":1769698356000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Influence of Chronic Kidney Disease on Platelet Reactivity Response to Clopidogrel and Ticagrelor"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3201-9561","authenticated-orcid":false,"given":"Andr\u00e9","family":"Franci","sequence":"first","affiliation":[{"name":"Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo CEP 05403-000, Brazil"},{"name":"Centro de Cardiologia, Hospital S\u00edrio-Liban\u00eas, Sao Paulo CEP 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-9902","authenticated-orcid":false,"given":"Roberto","family":"Giraldez","sequence":"additional","affiliation":[{"name":"Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo CEP 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Hospital do Coracao do Brasil, Brasilia CEP 70390-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0525-0506","authenticated-orcid":false,"given":"Talia","family":"Dal\u00e7\u00f3quio","sequence":"additional","affiliation":[{"name":"Centro de Cardiologia, Hospital S\u00edrio-Liban\u00eas, Sao Paulo CEP 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Genestreti","sequence":"additional","affiliation":[{"name":"Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo CEP 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-8759","authenticated-orcid":false,"given":"Aline","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Centro de Cardiologia, Hospital S\u00edrio-Liban\u00eas, Sao Paulo CEP 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1641-135X","authenticated-orcid":false,"given":"Fernando","family":"Menezes","sequence":"additional","affiliation":[{"name":"Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo CEP 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo","family":"Furtado","sequence":"additional","affiliation":[{"name":"Centro de Cardiologia, Hospital S\u00edrio-Liban\u00eas, Sao Paulo CEP 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8148-2803","authenticated-orcid":false,"given":"Danilo","family":"Sarti","sequence":"additional","affiliation":[{"name":"Royal College of Surgeons in Ireland, University of Medicine and Heath Sciences\u2013Stephen\u2019s Green, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-1755","authenticated-orcid":false,"given":"Luciano","family":"Baracioli","sequence":"additional","affiliation":[{"name":"Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo CEP 05403-000, Brazil"},{"name":"Centro de Cardiologia, Hospital S\u00edrio-Liban\u00eas, Sao Paulo CEP 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-3689","authenticated-orcid":false,"given":"Jos\u00e9","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo CEP 05403-000, Brazil"},{"name":"Centro de Cardiologia, Hospital S\u00edrio-Liban\u00eas, Sao Paulo CEP 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","first-page":"1008","article-title":"A critical review of chronic kidney disease as a risk factor for coronary artery disease","volume":"35","author":"Coyle","year":"2021","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1161\/CIRCULATIONAHA.118.032078","article-title":"P2Y12-ADP Receptor Blockade in Chronic Kidney Disease Patients with Acute Coronary Syndromes","volume":"138","author":"Bonello","year":"2018","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/S0735-1097(02)01745-X","article-title":"The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions","volume":"39","author":"Best","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.jacc.2021.08.074","article-title":"Duration of Dual Antiplatelet Therapy for Patients at High Bleeding Risk Undergoing PCI","volume":"78","author":"Valgimigli","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1056\/NEJMoa2507980","article-title":"Early Withdrawal of Aspirin after PCI in Acute Coronary Syndromes","volume":"393","author":"Franken","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1016\/j.jacc.2021.09.006","article-title":"2021 ACC\/AHA\/SCAI Guideline for Coronary Artery Revascularization","volume":"79","author":"Lawton","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, J.J., Gao, X.F., Ge, Z., Tian, N.L., Liu, Z.Z., Lin, S., Ye, F., and Chen, S.L. (2016). High platelet reactivity affects the clinical outcomes of patients undergoing percutaneous coronary intervention. BMC Cardiovasc. Disord., 16.","DOI":"10.1186\/s12872-016-0394-0"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gao, X.F., Lu, S., Ge, Z., Zuo, G.F., Wang, Z.M., Wang, F., Kong, X.Q., Chai, D.Y., Chen, S.L., and Zhang, J.J. (2018). Relationship between high platelet reactivity on clopidogrel and long-term clinical outcomes after drug-eluting stents implantation (PAINT-DES): A prospective propensity score-matched cohort study. BMC Cardiovasc. Disord., 18.","DOI":"10.1186\/s12872-018-0841-1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1161\/CIRCULATIONAHA.111.029165","article-title":"Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: A time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial","volume":"124","author":"Price","year":"2011","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/j.jacc.2007.05.049","article-title":"Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease","volume":"50","author":"Angiolillo","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e001683","DOI":"10.1161\/CIRCINTERVENTIONS.115.001683","article-title":"Prevalence and impact of high platelet reactivity in chronic kidney disease: Results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry","volume":"8","author":"Baber","year":"2015","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e002760","DOI":"10.1161\/CIRCINTERVENTIONS.115.002760","article-title":"Defining the link between chronic kidney disease, high platelet reactivity, and clinical outcomes in clopidogrel-treated patients undergoing percutaneous coronary intervention","volume":"8","author":"Franchi","year":"2015","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_14","first-page":"CD008834","article-title":"Antiplatelet agents for chronic kidney disease","volume":"2","author":"Natale","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1161\/CIRCULATIONAHA.109.933796","article-title":"Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: Results from the Platelet Inhibition and Patient Outcomes (PLATO) trial","volume":"122","author":"James","year":"2010","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"461","DOI":"10.7326\/0003-4819-130-6-199903160-00002","article-title":"A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation","volume":"130","author":"Levey","year":"1999","journal-title":"Ann. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1161\/CIRCULATIONAHA.110.974683","article-title":"Ticagrelor in the renal dysfunction subgroup: Subjugated or substantiated?","volume":"122","author":"Montalescot","year":"2010","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.amjcard.2009.06.049","article-title":"A comparison of clopidogrel responsiveness in patients with versus without chronic renal failure","volume":"104","author":"Park","year":"2009","journal-title":"Am. J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/bcp.13436","article-title":"Pharmacodynamics and pharmacokinetics of ticagrelor vs. clopidogrel in patients with acute coronary syndromes and chronic kidney disease","volume":"84","author":"Wang","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.vph.2015.10.006","article-title":"Novara Atherosclerosis Study Group (NAS). Platelet reactivity in patients with impaired renal function receiving dual antiplatelet therapy with clopidogrel or ticagrelor","volume":"79","author":"Barbieri","year":"2016","journal-title":"Vasc. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1161\/CIRCULATIONAHA.109.912550","article-title":"Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: The ONSET\/OFFSET study","volume":"120","author":"Gurbel","year":"2009","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1177\/0091270011415526","article-title":"Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment","volume":"52","author":"Butler","year":"2012","journal-title":"J. Clin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1681\/ASN.2020101440","article-title":"Platelet Function in CKD: A Systematic Review and Meta-Analysis","volume":"32","author":"Baaten","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1093\/eurheartj\/ehn046","article-title":"Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation","volume":"29","author":"Price","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1111\/j.1538-7836.2010.03809.x","article-title":"Clinical implications of clopidogrel non-response in cardiovascular patients: A systematic review and meta-analysis","volume":"8","author":"Combescure","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/eurheartj\/ehv104","article-title":"Bleeding and stent thrombosis on P2Y12-inhibitors: Collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention","volume":"36","author":"Aradi","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_27","first-page":"204","article-title":"Platelet reactivity and cardiovascular events after percutaneous coronary intervention in patients with stable coronary artery disease: The Stent Thrombosis In Belgium (STIB) trial","volume":"10","author":"Legrand","year":"2014","journal-title":"Eur. Interv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.acvd.2014.03.004","article-title":"Thrombotic and bleeding events after coronary stenting according to clopidogrel and aspirin platelet reactivity: VerifyNow French Registry (VERIFRENCHY)","volume":"107","author":"Yayehd","year":"2014","journal-title":"Arch. Cardiovasc. Dis."},{"key":"ref_29","first-page":"844","article-title":"Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel. Systematic review and meta-analysis of individual patient data","volume":"115","author":"Reny","year":"2016","journal-title":"Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1161\/CIRCULATIONAHA.112.112094","article-title":"Platelet function testing in patients with coronary artery disease: Is the Who and the When any clearer than the What and the What then?","volume":"125","author":"Rade","year":"2012","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.jacc.2009.10.043","article-title":"Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy","volume":"55","author":"Angiolillo","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/clc.23588","article-title":"Impact of renal function on residual platelet reactivity and clinical outcomes in patients with acute coronary syndrome treated with clopidogrel","volume":"44","author":"Li","year":"2021","journal-title":"Clin. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.ahj.2007.10.046","article-title":"The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: Results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial","volume":"155","author":"Best","year":"2008","journal-title":"Am. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.amjcard.2009.01.342","article-title":"Clinical outcomes of patients with diabetic nephropathy randomized to clopidogrel plus aspirin versus aspirin alone (a post hoc analysis of the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance [CHARISMA] trial)","volume":"103","author":"Dasgupta","year":"2009","journal-title":"Am. J. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"445","DOI":"10.7326\/0003-4819-156-6-201203200-00007","article-title":"Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: A systematic review and meta-analysis","volume":"156","author":"Palmer","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1056\/NEJMoa0904327","article-title":"Ticagrelor versus clopidogrel in patients with acute coronary syndromes","volume":"361","author":"Wallentin","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s40256-023-00600-w","article-title":"Ticagrelor or Clopidogrel as Antiplatelet Agents in Patients with Chronic Kidney Disease and Cardiovascular Disease: A Meta-analysis","volume":"23","author":"Guo","year":"2023","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tamakauskas, V., \u017dali\u016bnas, R., Lesauskait\u0117, V., Kupstyt\u0117-Kri\u0161tapon\u0117, N., \u0160akalyt\u0117, G., Jurgaityt\u0117, J., \u010ciapien\u0117, I., and Tatar\u016bnas, V. (2022). Factors Determining Ticagrelor-Induced Dyspnea in Patients with Acute Coronary Syndrome. Appl. Sci., 12.","DOI":"10.3390\/app121910021"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.amjcard.2006.03.054","article-title":"Onset and offset of platelet inhibition after high-dose clopidogrel loading and standard daily therapy measured by a point-of-care assay in healthy volunteers","volume":"98","author":"Price","year":"2006","journal-title":"Am. J. Cardiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1359\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T05:15:31Z","timestamp":1769836531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031359"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031359","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]}}}