{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:49:59Z","timestamp":1788194999932,"version":"build-2803163510"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Quality and Outcomes"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Knowledge about drug\u2013drug interactions commonly arises from preclinical trials, from adverse drug reports, or based on knowledge of mechanisms of action. Our aim was to investigate whether drug\u2013drug interactions were discoverable without prior hypotheses using data mining. We focused on warfarin\u2013drug interactions as the prototype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>We analyzed altered prothrombin time (measured as international normalized ratio [INR]) after initiation of a novel prescription in previously INR-stable warfarin-treated patients with nonvalvular atrial fibrillation. Data sets were retrieved from clinical work. Random forest (a machine-learning method) was set up to predict altered INR levels after novel prescriptions. The most important drug groups from the analysis were further investigated using logistic regression in a new data set. Two hundred and twenty drug groups were analyzed in 61\u2009190 novel prescriptions. We rediscovered 2 drug groups having known interactions (\u03b2-lactamase-resistant penicillins [dicloxacillin] and carboxamide derivatives) and 3 antithrombotic\/anticoagulant agents (platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors [dabigatran etexilate], and heparins) causing decreasing INR. Six drug groups with known interactions were rediscovered causing increasing INR (antiarrhythmics class III [amiodarone], other opioids [tramadol], glucocorticoids, triazole derivatives, and combinations of penicillins, including \u03b2-lactamase inhibitors) and two had a known interaction in a closely related drug group (oripavine derivatives [buprenorphine] and natural opium alkaloids). Antipropulsives had an unknown signal of increasing INR.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>We were able to identify known warfarin\u2013drug interactions without a prior hypothesis using clinical registries. Additionally, we discovered a few potentially novel interactions. This opens up for the use of data mining to discover unknown drug\u2013drug interactions in cardiovascular medicine.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circoutcomes.116.003055","type":"journal-article","created":{"date-parts":[[2016,11,9]],"date-time":"2016-11-09T13:18:34Z","timestamp":1478697514000},"page":"621-628","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Identifying Drug\u2013Drug Interactions by Data Mining"],"prefix":"10.1161","volume":"9","author":[{"given":"Peter W\u00e6de","family":"Hansen","sequence":"first","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Clemmensen","sequence":"additional","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.G.","family":"Sehested","sequence":"additional","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil Loldrup","family":"Fosb\u00f8l","sequence":"additional","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Torp-Pedersen","sequence":"additional","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"K\u00f8ber","sequence":"additional","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar H.","family":"Gislason","sequence":"additional","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Andersson","sequence":"additional","affiliation":[{"name":"From the Danish Heart Foundation, Copenhagen, Denmark (P.W.H., T.S.G.S., E.L.F., G.H.G.); DTU Compute, Technical University of Denmark, Lyngby (L.C.); The Heart Centre, Rigshospitalet (E.L.F., L.K.), and Department of Clinical Medicine (G.H.G.), University of Copenhagen, Denmark; Institute of Health, Science and Technology, Aalborg University, Denmark (C.T.-P.); The National Institute of Public Health, University of Southern Denmark, Copenhagen (G.H.G.); University of Copenhagen, Denmark; and..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-013-9470-x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200629050-00003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","unstructured":"Jensen DD Cohen PR. 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