{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:06:22Z","timestamp":1789506382668,"version":"build-2803163510"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Despite reductions in door\u2010to\u2010balloon times for primary coronary intervention, mortality from ST\u2010segment\u2013elevation myocardial infarction has plateaued. Early pre\u2013primary coronary intervention treatment of ST\u2010segment\u2013elevation myocardial infarction with glycoprotein IIb\/IIIa inhibitors improves pre\u2013primary coronary intervention coronary flow, limits infarct size, and improves survival. We report the first human use of a novel glycoprotein IIb\/IIIa inhibitor designed for subcutaneous first point\u2010of\u2010care ST\u2010segment\u2013elevation myocardial infarction treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Healthy volunteers and patients with stable coronary artery disease receiving aspirin received escalating doses of RUC\u20104 or placebo in a sentinel\u2010dose, randomized, blinded fashion. Inhibition of platelet aggregation (IPA) to ADP (20\u00a0\u03bcmol\/L), RUC\u20104 blood levels, laboratory evaluations, and clinical assessments were made through 24\u00a0hours and at 7\u00a0days. Doses were increased until reaching the biologically effective dose (the dose producing \u226580% IPA within 15\u00a0minutes, with return toward baseline within 4\u00a0hours). In healthy volunteers, 15\u00a0minutes after subcutaneous injection, mean\u00b1SD IPA was 6.9%+7.1% after placebo and 71.8%\u00b115.0% at 0.05\u00a0mg\/kg (n=6) and 84.7%\u00b116.7% at 0.075\u00a0mg\/kg (n=6) after RUC\u20104. IPA diminished over 90 to 120\u00a0minutes. In patients with coronary artery disease, 15\u00a0minutes after subcutaneous injection of placebo or 0.04\u00a0mg\/kg (n=2), 0.05\u00a0mg\/kg (n=6), and 0.075\u00a0mg\/kg (n=18) of RUC\u20104, IPA was 14.6%\u00b111.7%, 53.6%\u00b117.0%, 76.9%\u00b110.6%, and 88.9%\u00b112.7%, respectively. RUC\u20104 blood levels correlated with IPA. Aspirin did not affect IPA or RUC\u20104 blood levels. Platelet counts were stable and no serious adverse events, bleeding, or injection site reactions were observed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">RUC\u20104 provides rapid, high\u2010grade, limited\u2010duration platelet inhibition following subcutaneous administration that appears to be safe and well tolerated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\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.clini\u200bcaltr\u200bials.gov<\/jats:ext-link>\n              ; Unique identifier: NTC03844191.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.016552","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:15:22Z","timestamp":1598433322000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["First Human Use of RUC\u20104: A Nonactivating Second\u2010Generation Small\u2010Molecule Platelet Glycoprotein IIb\/IIIa (Integrin \u03b1IIb\u03b23) Inhibitor Designed for Subcutaneous Point\u2010of\u2010Care Treatment of ST\u2010Segment\u2013Elevation Myocardial Infarction"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-127X","authenticated-orcid":false,"given":"Dean J.","family":"Kereiakes","sequence":"first","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1123-0533","authenticated-orcid":false,"given":"Tim D.","family":"Henry","sequence":"additional","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"DeMaria","sequence":"additional","affiliation":[{"name":"UC San Diego Health La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad","family":"Bentur","sequence":"additional","affiliation":[{"name":"Allen and Frances Adler Laboratory of Blood and Vascular Biology Rockefeller University New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Carlson","sequence":"additional","affiliation":[{"name":"Precision for Medicine Carlsbad CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Seng Yue","sequence":"additional","affiliation":[{"name":"Learn and Confirm Inc. Saint\u2010Laurent Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda H.","family":"Martin","sequence":"additional","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Midkiff","sequence":"additional","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Mueller","sequence":"additional","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terah","family":"Meek","sequence":"additional","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Garza","sequence":"additional","affiliation":[{"name":"The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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