{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:05:58Z","timestamp":1785222358245,"version":"3.55.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":1909,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aims of this study were to evaluate if the risk of cardiovascular events and all-cause mortality was higher in the presence of hyperkalaemia (HK) in patients with heart failure (HF) treated with renin\u2013angiotensin\u2013aldosterone system inhibitors (RAASi), and to investigate in this cohort the increased risk of cardiovascular events and all-cause mortality among HK patients with non-optimal adherence to RAASi therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this retrospective cohort study based on administrative databases of five Italian Local Health Units, all adult patients with a HF diagnosis between January 2010 and December 2017 were included only if they were prescribed RAASi therapy during the first 3\u2009months after the index date, that corresponded to the date of first HF diagnosis during the inclusion period. Patients were considered to have HK if serum potassium level was \u22655.5\u2009mmol\/L. A propensity score matching was applied before evaluation of hazard ratios. Patients with HK were 37% (P\u2009&amp;lt;\u20090.001) and 70% (P\u2009&amp;lt;\u20090.001), respectively, more at risk of cardiovascular events and of dying for all-cause mortality compared to non-HK patients. Among the HK group, patients non-adherent to RAASi therapy had a 39% (P = 0.105) higher risk of cardiovascular events and a twofold increased risk (P\u2009&amp;lt;\u20090.001) of all-cause death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Findings from this real-world study showed that in a cohort of HF patients under RAASi therapy, subjects with HK had an enhanced risk of cardiovascular events or death compared to patients without HK. Moreover, in HK patients, sub-optimal adherence to RAASi therapy was associated with an increased risk of all-cause mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2024","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T07:58:37Z","timestamp":1602662317000},"page":"2049-2055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Effects of Hyperkalaemia and Non-Adherence to Renin\u2013Angiotensin\u2013Aldosterone System Inhibitor Therapy in Patients with Heart Failure in Italy: A Propensity-Matched Study"],"prefix":"10.1093","volume":"22","author":[{"given":"Maurizio","family":"Volterrani","sequence":"first","affiliation":[{"name":"Department of Cardiology, IRCCS San Raffaele Pisana , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Perrone","sequence":"additional","affiliation":[{"name":"CliCon Srl Health, Economics & Outcomes Research , Ravenna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"CliCon Srl Health, Economics & Outcomes Research , Ravenna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Giacomini","sequence":"additional","affiliation":[{"name":"CliCon Srl Health, Economics & Outcomes Research , Ravenna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Iellamo","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Translational Medicine, Tor Vergata University , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Degli Esposti","sequence":"additional","affiliation":[{"name":"CliCon Srl Health, Economics & Outcomes Research , Ravenna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on the behalf of a LHUs Study Group (see Appendix)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"2026011721382196800_ejhf2024-bib-0001","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1093\/eurheartj\/ehs257","article-title":"Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice","volume":"33","author":"Zannad","year":"2012","journal-title":"Eur Heart J"},{"key":"2026011721382196800_ejhf2024-bib-0002","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026011721382196800_ejhf2024-bib-0003","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.amjmed.2008.10.028","article-title":"The management of hyperkalemia in patients with cardiovascular disease","volume":"122","author":"Khanna","year":"2009","journal-title":"Am J Med"},{"key":"2026011721382196800_ejhf2024-bib-0004","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1056\/NEJMra035279","article-title":"Managing hyperkalemia caused by inhibitors of the renin\u2013angiotensin\u2013aldosterone system","volume":"351","author":"Palmer","year":"2004","journal-title":"N Engl J Med"},{"key":"2026011721382196800_ejhf2024-bib-0005","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.kisu.2016.01.004","article-title":"Hyperkalemia constitutes a constraint for implementing renin\u2013angiotensin\u2013aldosterone inhibition: the widening gap between mandated treatment guidelines and the real-world clinical arena","volume":"6","author":"Epstein","year":"2016","journal-title":"Kidney Int Suppl (2011)"},{"key":"2026011721382196800_ejhf2024-bib-0006","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.119.012655","article-title":"Real-world associations of renin\u2013angiotensin\u2013aldosterone system inhibitor dose, hyperkalemia, and adverse clinical outcomes in a cohort of patients with new-onset chronic kidney disease or heart failure in the United Kingdom","volume":"8","author":"Linde","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"2026011721382196800_ejhf2024-bib-0007","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/eurheartj\/ehx026","article-title":"Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study","volume":"38","author":"Ouwerkerk","year":"2017","journal-title":"Eur Heart J"},{"key":"2026011721382196800_ejhf2024-bib-0008","volume-title":"Guideline for the Classification and Conduction of the Observational Studies on Medicines","author":"Agenzia Italiana del Farmaco (AIFA)","year":"2008"},{"key":"2026011721382196800_ejhf2024-bib-0009","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/MLR.0b013e31829b1d2a","article-title":"Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases","volume":"51","author":"Raebel","year":"2013","journal-title":"Med Care"},{"key":"2026011721382196800_ejhf2024-bib-0010"},{"key":"2026011721382196800_ejhf2024-bib-0011","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J Chronic Dis"},{"key":"2026011721382196800_ejhf2024-bib-0012","article-title":"Effect of hyperkalemia and RAASi nonadherence on patients affected by heart failure or chronic kidney disease","volume":"36","author":"Degli Esposti","year":"2019","journal-title":"G Ital Nefrol"},{"key":"2026011721382196800_ejhf2024-bib-0013","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000479802","article-title":"Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and\/or diabetes","volume":"46","author":"Collins","year":"2017","journal-title":"Am J Nephrol"},{"key":"2026011721382196800_ejhf2024-bib-0014","doi-asserted-by":"crossref","first-page":"220","DOI":"10.2215\/CJN.00030117","article-title":"Serum potassium and cardiovascular outcomes: the highs and the lows","volume":"12","author":"Toto","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026011721382196800_ejhf2024-bib-0015","first-page":"S212","article-title":"Evaluation of the treatment gap between clinical guidelines and the utilization of renin\u2013angiotensin\u2013aldosterone system inhibitors","volume":"21","author":"Epstein","year":"2015","journal-title":"Am J Manag Care"},{"key":"2026011721382196800_ejhf2024-bib-0016","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1093\/eurheartj\/ehv268","article-title":"Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study","volume":"36","author":"Edner","year":"2015","journal-title":"Eur Heart J"},{"key":"2026011721382196800_ejhf2024-bib-0017","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/ejhf.1079","article-title":"Potassium and the use of renin\u2013angiotensin\u2013aldosterone system inhibitors in heart failure with reduced ejection fraction: data from BIOSTAT-CHF: potassium and RAAS inhibitors in HFrEF","volume":"20","author":"Beusekamp","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2026011721382196800_ejhf2024-bib-0018","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1161\/CIRCHEARTFAILURE.114.001104","article-title":"Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist","volume":"7","author":"Vardeny","year":"2014","journal-title":"Circ Heart Fail"},{"key":"2026011721382196800_ejhf2024-bib-0019","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1056\/NEJMoa040135","article-title":"Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study","volume":"351","author":"Juurlink","year":"2004","journal-title":"N Engl J Med"},{"key":"2026011721382196800_ejhf2024-bib-0020","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1161\/CIRCHEARTFAILURE.113.000792","article-title":"Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)","volume":"7","author":"Rossignol","year":"2014","journal-title":"Circ Heart Fail"},{"key":"2026011721382196800_ejhf2024-bib-0021","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/ejhf.402","article-title":"Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors","volume":"17","author":"Pitt","year":"2015","journal-title":"Eur J Heart Fail"},{"key":"2026011721382196800_ejhf2024-bib-0022","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/ejhf.300","article-title":"Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial","volume":"17","author":"Anker","year":"2015","journal-title":"Eur J Heart Fail"},{"key":"2026011721382196800_ejhf2024-bib-0023","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1161\/CIRCULATIONAHA.105.580506","article-title":"Renal function as a predictor of outcome in a broad spectrum of patients with heart failure","volume":"113","author":"Hillege","year":"2006","journal-title":"Circulation"},{"key":"2026011721382196800_ejhf2024-bib-0024","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.ahj.2006.02.028","article-title":"Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial","volume":"151","author":"McMurray","year":"2006","journal-title":"Am Heart J"},{"key":"2026011721382196800_ejhf2024-bib-0025","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1016\/j.jacc.2007.07.067","article-title":"Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program","volume":"50","author":"Desai","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2026011721382196800_ejhf2024-bib-0026","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacc.2005.06.010","article-title":"The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure","volume":"46","author":"Shah","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"2026011721382196800_ejhf2024-bib-0027","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/pds.1217","article-title":"Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor blockers","volume":"16","author":"Raebel","year":"2007","journal-title":"Pharmacoepidemiol Drug Saf"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2024","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.2024","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/22\/11\/2049\/66110845\/eurjhf_22_11_2049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/22\/11\/2049\/66110845\/eurjhf_22_11_2049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:40:51Z","timestamp":1768704051000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/22\/11\/2049\/8384581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,27]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,10,27]]},"published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.2024","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,11]]},"published":{"date-parts":[[2020,10,27]]},"assertion":[{"value":"2020-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}