{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:00:27Z","timestamp":1787065227786,"version":"build-2736575974"},"reference-count":30,"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":1937,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"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 associations between potassium level and outcomes, the effect of sacubitril\u2013valsartan on potassium level, and whether potassium level modified the effect of sacubitril\u2013valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM-HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non-cardiovascular death and heart failure hospitalization, were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A total of 8399 patients were randomized to either enalapril or sacubitril\u2013valsartan. Potassium level at randomization and follow-up was examined as a continuous and categorical variable (\u22643.5, 3.6\u20134.0, 4.1\u20134.9, 5.0\u20135.4 and \u22655.5\u2009mmol\/L) in various statistical models. Hyperkalaemia was defined as K+\u2009\u22655.5\u2009mmol\/L and hypokalaemia as K+\u2009\u22643.5\u2009mmol\/L. Compared with potassium 4.1\u20134.9\u2009mmol\/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84\u20133.14] and hyperkalaemia (HR 1.42, 95% CI 1.10\u20131.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non-cardiovascular death and heart failure hospitalization. Sacubitril\u2013valsartan had no effect on potassium overall. The benefit of sacubitril\u2013valsartan over enalapril was consistent across the range of baseline potassium levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1987","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T07:28:24Z","timestamp":1598599704000},"page":"2056-2064","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Serum Potassium in the PARADIGM-HF Trial"],"prefix":"10.1093","volume":"22","author":[{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"National Institute of Health and Medical Research, Centre for Clinical Multidisciplinary Research, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists , Nancy ,","place":["France"]},{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik M.","family":"Mogensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, Copenhagen University Hospital , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pardeep S.","family":"Jhund","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Lucien","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute , Montreal, QC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina and Ralph H. Johnson Department of Veterans Affairs Medical Center , Charleston, SC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"National Institute of Health and Medical Research, Centre for Clinical Multidisciplinary Research, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"National Institute of Health and Medical Research, Centre for Clinical Multidisciplinary Research, INSERM U1116, University of Lorraine, Regional University Hospital of Nancy, French Clinical Research Infrastructure Network Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center , Dallas, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"2026011721381806700_ejhf1987-bib-0001","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":"2026011721381806700_ejhf1987-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":"2026011721381806700_ejhf1987-bib-0003","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.jacc.2016.05.011","article-title":"2016 ACC\/AHA\/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF\/AHA guideline for the Management of Heart Failure: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America","volume":"68","author":"Yancy","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"2026011721381806700_ejhf1987-bib-0004","doi-asserted-by":"crossref","first-page":"A55","DOI":"10.1093\/eurheartj\/suy034","article-title":"Potassium binders for the prevention of hyperkalaemia in heart failure patients: implementation issues and future developments","volume":"21","author":"Zannad","year":"2019","journal-title":"Eur Heart J Suppl"},{"key":"2026011721381806700_ejhf1987-bib-0005","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":"2026011721381806700_ejhf1987-bib-0006","first-page":"104","article-title":"Short-term mortality risk of serum potassium levels in hypertension: a retrospective analysis of nationwide registry data","volume":"38","author":"Krogager","year":"2016","journal-title":"Eur Heart J"},{"key":"2026011721381806700_ejhf1987-bib-0007","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1001\/jama.2011.1967","article-title":"Serum potassium levels and mortality in acute myocardial infarction","volume":"307","author":"Goyal","year":"2012","journal-title":"JAMA"},{"key":"2026011721381806700_ejhf1987-bib-0008","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1093\/eurheartj\/ehx537","article-title":"Serum potassium in patients with chronic heart failure: once we make a U-turn where should we go?","volume":"38","author":"Pitt","year":"2017","journal-title":"Eur Heart J"},{"key":"2026011721381806700_ejhf1987-bib-0009","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/eurheartj\/ehy100","article-title":"CKD Prognosis Consortium. Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis","volume":"39","author":"Kovesdy","year":"2018","journal-title":"Eur Heart J"},{"key":"2026011721381806700_ejhf1987-bib-0010","first-page":"c8","article-title":"Association of hypo- and hyperkalemia with disease progression and mortality in males with chronic kidney disease: the role of race","volume":"120","author":"Hayes","year":"2012","journal-title":"Nephron Clin Pract"},{"key":"2026011721381806700_ejhf1987-bib-0011","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1177\/0003319717740004","article-title":"Potassium fluctuations are associated with inhospital mortality from acute myocardial infarction. Soroka Acute Myocardial Infarction II (SAMI-II) Project","volume":"69","author":"Shiyovich","year":"2018","journal-title":"Angiology"},{"key":"2026011721381806700_ejhf1987-bib-0012","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jash.2017.09.011","article-title":"Potassium homeostasis in health and disease: a scientific workshop cosponsored by the National Kidney Foundation and the American Society of Hypertension","volume":"11","author":"Kovesdy","year":"2017","journal-title":"J Am Soc Hypertens"},{"key":"2026011721381806700_ejhf1987-bib-0013","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin-neprilysin inhibition versus enalapril in heart failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"2026011721381806700_ejhf1987-bib-0014","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF00561373","article-title":"Atrial natriuretic factor inhibits ACTH stimulated aldosterone but not cortisol secretion in man","volume":"35","author":"McMurray","year":"1988","journal-title":"Eur J Clin Pharmacol"},{"key":"2026011721381806700_ejhf1987-bib-0015","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1042\/cs0700507","article-title":"Atrial natriuretic peptide inhibits the aldosterone response to angiotensin II in man","volume":"70","author":"Anderson","year":"1986","journal-title":"Clin Sci (Lond)"},{"key":"2026011721381806700_ejhf1987-bib-0016","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-3462-1","volume-title":"Regression Modeling Strategies: With Applications to Linear Models Logistic Regression and Survival Analysis","author":"Harrell","year":"2001"},{"key":"2026011721381806700_ejhf1987-bib-0017","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1001\/jama.2018.21554","article-title":"Using the E-value to assess the potential effect of unmeasured confounding in observational studies","volume":"321","author":"Haneuse","year":"2019","journal-title":"JAMA"},{"key":"2026011721381806700_ejhf1987-bib-0018","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1093\/eurheartj\/ehx460","article-title":"Associations of serum potassium levels with mortality in chronic heart failure patients","volume":"38","author":"Aldahl","year":"2017","journal-title":"Eur Heart J"},{"key":"2026011721381806700_ejhf1987-bib-0019","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1161\/CIRCULATIONAHA.117.030576","article-title":"Long-term potassium monitoring and dynamics in heart failure and risk of mortality","volume":"137","author":"Nunez","year":"2018","journal-title":"Circulation"},{"key":"2026011721381806700_ejhf1987-bib-0020","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jchf.2018.10.003","article-title":"Incidence predictors and outcome associations of dyskalemia in heart failure with preserved, mid-range and reduced ejection fraction","volume":"7","author":"Savarese","year":"2019","journal-title":"JACC Heart Fail"},{"key":"2026011721381806700_ejhf1987-bib-0021","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1016\/j.jacc.2020.04.021","article-title":"Abnormalities of potassium in heart failure: JACC state-of-the-art review","volume":"75","author":"Ferreira","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2026011721381806700_ejhf1987-bib-0022","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/ejhf.1757","article-title":"Association between potassium level and outcomes in heart failure with reduced ejection fraction: a cohort study from the Swedish Heart Failure Registry","volume":"22","author":"Cooper","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"2026011721381806700_ejhf1987-bib-0023","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1002\/ejhf.1793","article-title":"Unravelling the interplay between hyperkalaemia renin\u2013angiotensin\u2013aldosterone inhibitor use and clinical outcomes. Data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry","volume":"22","author":"Rossignol","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"2026011721381806700_ejhf1987-bib-0024","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0033-0620(66)80029-4","article-title":"Potassium and the monophasic action potential electrocardiogram conduction and arrhythmias","volume":"8","author":"Fisch","year":"1966","journal-title":"Prog Cardiovasc Dis"},{"key":"2026011721381806700_ejhf1987-bib-0025","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jacc.2003.06.021","article-title":"What is the optimal serum potassium level in cardiovascular patients?","volume":"43","author":"Macdonald","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"2026011721381806700_ejhf1987-bib-0026","doi-asserted-by":"crossref","first-page":"e004667","DOI":"10.1161\/CIRCEP.116.004667","article-title":"Electrophysiology of hypokalemia and hyperkalemia","volume":"10","author":"Weiss","year":"2017","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2026011721381806700_ejhf1987-bib-0027","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/ejhf.688","article-title":"Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia","volume":"19","author":"Rossignol","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2026011721381806700_ejhf1987-bib-0028","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1093\/eurheartj\/ehw226","article-title":"Geographic variations in the PARADIGM-HF heart failure trial","volume":"37","author":"Kristensen","year":"2016","journal-title":"Eur Heart J"},{"key":"2026011721381806700_ejhf1987-bib-0029","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0140-6736(20)30748-0","article-title":"Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials","volume":"396","author":"Vaduganathan","year":"2020","journal-title":"Lancet"},{"key":"2026011721381806700_ejhf1987-bib-0030","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1001\/jamacardio.2016.4733","article-title":"Reduced risk of hyperkalemia during treatment of heart failure with mineralocorticoid receptor antagonists by use of sacubitril\/valsartan compared with enalapril: a secondary analysis of the PARADIGM-HF trial","volume":"2","author":"Desai","year":"2017","journal-title":"JAMA Cardiol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.1987","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.1987","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/22\/11\/2056\/66110928\/eurjhf_22_11_2056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/22\/11\/2056\/66110928\/eurjhf_22_11_2056.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:40:43Z","timestamp":1768704043000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/22\/11\/2056\/8384576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,29]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,9,29]]},"published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.1987","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":[[2020,9,29]]},"assertion":[{"value":"2020-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}