{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:44:11Z","timestamp":1792827851543,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>BMS-986141 is a novel potent highly selective antagonist of PAR (protease-activated receptor) type 4. PAR4 antagonism has been demonstrated to reduce thrombus formation in isolation and in combination with factor Xa inhibition in high shear conditions in healthy people. We sought to determine whether PAR4 antagonism had additive antithrombotic effects in patients with coronary artery disease who were receiving antiplatelet therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Forty-five patients with stable coronary heart disease and 10 healthy volunteers completed a phase 2a open-label 4-arm single-center study. Patients were allocated to 1 of 3 treatment arms for 7 days: (1) ticagrelor (90 mg BID), (2) aspirin (75 mg QD), or (3) the combination of ticagrelor and aspirin. Agonist-induced platelet aggregation, platelet activation, and ex vivo thrombus formation were measured before and 2 and 24 hours after a single oral 4-mg dose of BMS-986141 on the first study visit day in all participants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              BMS-986141 demonstrated highly selective inhibition of PAR4-AP (agonist peptide)\u2013induced platelet aggregation, P-selectin expression, and platelet-monocyte aggregate expression (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              \u22640.001 for all), which were unaffected by concomitant antiplatelet therapies. PAR4 antagonism reduced ex vivo thrombus area in high shear conditions in healthy volunteers (\u221221%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.001) and in patients receiving ticagrelor alone (\u221228%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.001), aspirin alone (\u221223%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.018), or both in combination (\u221224%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              \u22640.001). Plasma concentration of BMS-986141 correlated with PAR4-AP\u2013induced platelet responses (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              \u22640.001 for all) and total thrombus area under high shear stress conditions (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              \u22640.01 for all).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>PAR4 antagonism has additive antithrombotic effects when used in addition to ticagrelor, aspirin, or their combination, in patients with stable coronary heart disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT05093790.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320448","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T10:01:06Z","timestamp":1707991266000},"page":"987-996","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["PAR4 Antagonism in Patients With Coronary Artery Disease Receiving Antiplatelet Therapies"],"prefix":"10.1161","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct05093790","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7523-1127","authenticated-orcid":true,"given":"Jennifer","family":"Nash","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-9972","authenticated-orcid":true,"given":"Mohammed N.","family":"Meah","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2833-5980","authenticated-orcid":true,"given":"Beth","family":"Whittington","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."},{"name":"WorldWide Patient Safety (B.W.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7834-8766","authenticated-orcid":true,"given":"Samuel","family":"Debono","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Raftis","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-597X","authenticated-orcid":true,"given":"Mark R.","family":"Miller","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Sorbie","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0533-7991","authenticated-orcid":true,"given":"Nicholas L.","family":"Mills","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josselin","family":"Nespoux","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Bruce","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodger","family":"Duffin","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-6603","authenticated-orcid":true,"given":"Neeraj","family":"Dhaun","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairi","family":"Brittan","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longfei","family":"Chao","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics (L.C., S.M.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6659-3687","authenticated-orcid":true,"given":"Samira","family":"Merali","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics (L.C., S.M.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational Medicine (M.K., Z.W.), Bristol Myers Squibb, Lawrenceville, NJ."},{"name":"Early Cardiovascular Clinical Development, R&amp;D (M.K.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1515-4945","authenticated-orcid":true,"given":"Zhaoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Medicine (M.K., Z.W.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Global Biometrics and Data Sciences (Y.Z., S.J.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqiang","family":"Jin","sequence":"additional","affiliation":[{"name":"Global Biometrics and Data Sciences (Y.Z., S.J.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Kozinn","sequence":"additional","affiliation":[{"name":"Translational Medicine (M.K., Z.W.), Bristol Myers Squibb, Lawrenceville, NJ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-4628","authenticated-orcid":true,"given":"David E.","family":"Newby","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (J.N., M.N.M., B.W., S.D., J.R., M.R.M., A.S., N.L.M., J.N., L.B., R.D., N.D., M.B., D.E.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.09.017"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx393"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa575"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.06.039"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000375"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000471"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000029.pub4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60213-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/23969873221100032"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10081721"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000404"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-021-07213-y"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvaa038"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.033033"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225629"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf5294"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.3_suppl.18s"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310104"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00783.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2023.2222846"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2022.2088719"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/35092573"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314960"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.06.030"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300395"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03587.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.78.6.1431"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114277"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13293"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010358"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12703"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.47799"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.117.004437"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.123.320448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T18:42:04Z","timestamp":1748544124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.123.320448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1161\/ATVBAHA.123.320448"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.123.320448","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}