{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T11:02:36Z","timestamp":1770894156981,"version":"3.50.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,11,20]]},"abstract":"\n Background<\/jats:title>\n \n Digoxin use was shown to be associated with an increased risk of cardiovascular events in atrial fibrillation (\n AF<\/jats:styled-content>\n ). We hypothesized that digoxin may affect cardiovascular risk by increasing platelet activation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Post hoc analysis of a prospective study of anticoagulated\n patients with AF<\/jats:styled-content>\n . Patients were divided into 2 groups balanced for age, sex, and cardiovascular risk factors: digoxin users (n=132) and nonusers (n=388). Urinary excretion of 11\u2010dehydro\u2010thromboxane B\n 2<\/jats:sub>\n (TxB\n 2<\/jats:sub>\n ), a marker of platelet activation, and serum digoxin concentration (\n SDC<\/jats:styled-content>\n ) were measured. In vitro experiments were performed on platelets from healthy subjects and AF patients, which were incubated with scalar doses of digoxin (0.6\u20132.4\u00a0ng\/mL) with or without prestimulation with a sub\u2010threshold of collagen. Median 11\u2010dehydro\u2010TxB\n 2<\/jats:sub>\n was 105.0 (\n interquartile range,<\/jats:styled-content>\n 60.0\u2013190.0) ng\/mg creatinine, and median\n SDC<\/jats:styled-content>\n was 0.65 (\n interquartile range,<\/jats:styled-content>\n 0.40\u20131.00) ng\/mL. Urinary 11\u2010dehydro\u2010TxB\n 2<\/jats:sub>\n and\n SDC<\/jats:styled-content>\n were correlated (\n r<\/jats:italic>\n s<\/jats:sub>\n =0.350,\n P<\/jats:italic>\n <0.001). Patients in the upper tertile of\n SDC<\/jats:styled-content>\n showed higher 11\u2010dehydro\u2010TxB\n 2<\/jats:sub>\n compared with non\u2013digoxin users (\n P<\/jats:italic>\n =0.019). In vitro study showed an increased basal platelet activation in\n patients with AF<\/jats:styled-content>\n compared with\n healthy subjects<\/jats:styled-content>\n . Digoxin (2.4\u00a0ng\/mL) induced calcium mobilization,\n PAC<\/jats:styled-content>\n \u20101 (procaspase\u2010activating compound 1) and platelet aggregation in\n AF<\/jats:styled-content>\n patients but not in\n healthy subjects<\/jats:styled-content>\n . After pretreatment with a sub\u2010threshold of collagen, digoxin dose\u2010dependent induced calcium mobilization, arachidonic acid release, TxB\n 2<\/jats:sub>\n biosynthesis,\n PAC<\/jats:styled-content>\n \u20101 and soluble platelet selectin expression, and platelet aggregation, which were inhibited by antibody against digoxin.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We found a significant in\u00a0vivo correlation between\n SDC<\/jats:styled-content>\n and platelet activation. Supratherapeutic\n SDC<\/jats:styled-content>\n increased in\u00a0vitro platelet aggregation via calcium\u2010related phospholipase A\n 2<\/jats:sub>\n phosphorylation. Our findings may have clinical implications for AF patients treated with digoxin.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.009509","type":"journal-article","created":{"date-parts":[[2018,12,16]],"date-time":"2018-12-16T20:51:29Z","timestamp":1544993489000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Digoxin and Platelet Activation in Patients With Atrial Fibrillation: In Vivo and In Vitro Study"],"prefix":"10.1161","volume":"7","author":[{"given":"Daniele","family":"Pastori","sequence":"first","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Carnevale","sequence":"additional","affiliation":[{"name":"Department of Medical\u2010Surgical Sciences and Biotechnologies Sapienza University of Rome Latina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Nocella","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed Pozzilli (IS) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Bartimoccia","sequence":"additional","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Novo","sequence":"additional","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittoria","family":"Cammisotto","sequence":"additional","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Piconese","sequence":"additional","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Santulli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fortunata","family":"Vasaturo","sequence":"additional","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Violi","sequence":"additional","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"I Clinica Medica Department of Internal Medicine and Medical Specialties Sapienza University of Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Atherosclerosis in Atrial Fibrillation (ATHERO\u2010AF) Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/pcad.2002.31591"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.01.013"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.5603\/CJ.a2016.0016"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h4451"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.7.871"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.02.091"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.584"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.1987.tb00551.x"},{"key":"e_1_3_1_10_2","first-page":"R651","article-title":"Lack of effect of ouabain on calcium homeostasis in rat platelets: comparative study with human platelets","volume":"266","author":"Oshima T","year":"1994","unstructured":"Oshima T, Ishida T, Matsuura H, Ishida M, Ishibashi K, Ozono R, Watanabe M, Kajiyama G, Kanbe M. 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