{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:20:09Z","timestamp":1792419609558,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["EudraCT 2010\u2010020808\u201029"],"award-info":[{"award-number":["EudraCT 2010\u2010020808\u201029"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"],"award-info":[{"award-number":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Liquid chromatography\u2010mass spectrometry (LC\u2010MS\/MS) is an objective new technique to assess non\u2010adherence to medications. We used this method to study the prevalence, predictors and outcomes of non\u2010adherence in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      This study included 1296 patients with HFrEF from BIOSTAT\u2010CHF, a study that aimed to optimise guideline\u2010recommended therapies. Angiotensin\u2010converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, \u03b2\u2010blockers and loop diuretics were measured in a single spot urine sample at 9\u2009months using LC\u2010MS\/MS. The relationship between medication non\u2010adherence and the composite endpoint of all\u2010cause death or heart failure hospitalisation, over a median follow\u2010up of 21 months, was evaluated. Non\u2010adherence to at least one prescribed medication was observed in 45.9% of patients. The strongest predictor of non\u2010adherence was non\u2010adherence to any of the other medication classes (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u20090.0005). Regional differences within Europe were observed. On multivariable analyses, non\u2010adherence to ACEi\/ARBs and \u03b2\u2010blockers was associated with an increased risk of the composite endpoint [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.09\u20131.95,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.008 and HR 1.48, 95% CI 1.12\u20131.96,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.006, respectively). Non\u2010adherence to \u03b2\u2010blockers was also associated with an increased risk of death (HR 2.48, 95% CI 1.67\u20133.68,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u20090.0005). Patients who were non\u2010adherent to loop diuretics were healthier and had a decreased risk of the composite endpoint (HR 0.69, 95% CI 0.51\u20130.93,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.014). Non\u2010adherence to mineralocorticoid receptor antagonists was not related to any clinical outcome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Non\u2010adherence to medications, assessed by a single urine test, is common and predicts clinical outcomes in patients with HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2160","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T02:06:55Z","timestamp":1616551615000},"page":"1182-1190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Non\u2010adherence to heart failure medications predicts clinical outcomes: assessment in a single spot urine sample by liquid chromatography\u2010tandem mass spectrometry (results of a prospective multicentre study)"],"prefix":"10.1093","volume":"23","author":[{"given":"Pankaj","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Metabolic Medicine and Chemical Pathology, University Hospitals of Leicester NHS Trust, Department of Cardiovascular Sciences University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine and Chemical Pathology, University Hospitals of Leicester NHS Trust, Department of Cardiovascular Sciences University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Health Sciences University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing University of Glasgow, Glasgow Royal Infirmary  Glasgow UK"},{"name":"National Heart &amp; Lung Institute, Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"Medicine, University of Bergen Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Cardiology, University of Cyprus, Heart Failure Unit National and Kapodistrian University of Athens, School of Medicine, Attikon, University Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular &amp; Clinical Medicine Ninewells Hospital and Medical School  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"Cardiology, ASST Spedali Civili di Brescia, Department of Medical and Surgical Specialties Radiological Sciences and Public Health, University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Division of Heart Failure, Hypertension and Preventive Cardiology, Department of Cardiovascular Disease, Academic Hospital (CHU) Clinical Investigation Centre (Inserm\u2010CHU)  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"British Heart Foundation, Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre Cardiovascular Unit and University Hospitals of Leicester NHS Trust  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don J.L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Leicester Cancer Research Centre University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain B.","family":"Squire","sequence":"additional","affiliation":[{"name":"University of Leicester University Hospitals of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Science, University of Leicester, NIHR Leicester Biomedical Research Centre Cardiovascular Unit and University Hospitals of Leicester NHS Trust  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2011.04.011"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2005.01.021"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu364"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-012-9321-3"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.669101"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2008.10.001"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67760-4"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq015"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-016-0697-7"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-017-9656-x"},{"key":"e_1_2_5_12_1","first-page":"CD000011","article-title":"Interventions for enhancing medication adherence","volume":"11","author":"Nieuwlaat R","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/45.8.1224"},{"key":"e_1_2_5_14_1","first-page":"5","article-title":"LC\u2010MS\/MS in the clinical laboratory \u2010 where to from here?","volume":"32","author":"Grebe SK","year":"2011","journal-title":"Clin Biochem Rev"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2010.183"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.067"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2013-305063"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.531"},{"key":"e_1_2_5_19_1","unstructured":"NCAT.National Centre for Adherence Testing 2020.https:\/\/www.leicestersresearch.nhs.uk\/about\u2010us\u20102\/facilities\/national\u2010centre\u2010for\u2010drug\u2010adherence\u2010testing(24 March 2021)."},{"key":"e_1_2_5_20_1","volume-title":"Clarke's Analysis of Drugs and Poisons","author":"Moffat AC","year":"2011"},{"key":"e_1_2_5_21_1","first-page":"17","article-title":"A novel \u2018Dilute\u2010and\u2010Shoot\u2019 liquid chromatography\u2010tandem mass spectrometry method for the screening of antihypertensive drugs in urine","volume":"40","author":"Lawson AJ","year":"2016","journal-title":"J Anal Toxicol"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz748.0070"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.785"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.14712\/18059694.2019.46"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvaa071"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03520420066040"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f55"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09631"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-1453"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.592"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/1474515117707669"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002606"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi603"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.111.965152"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32835e2286"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy339"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bky090"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2160","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.2160","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2160","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:14:52Z","timestamp":1767701692000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejhf.2160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,3]]},"references-count":36,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/ejhf.2160"],"URL":"https:\/\/doi.org\/10.1002\/ejhf.2160","archive":["Portico"],"relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,3]]},"assertion":[{"value":"2021-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}