Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist
Mineralocorticoid receptor antagonists reduce morbidity and mortality in patients with heart failure but can cause hyperkalemia, which contributes to reduced use of these drugs. Hypokalemia also leads to worse outcomes in patients with heart failure and may be attenuated by mineralocorticoid recepto...
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| Veröffentlicht in: | Circulation. Heart failure 2014-07, Vol.7 (4), p.573-579 |
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| container_title | Circulation. Heart failure |
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| creator | Vardeny, Orly Claggett, Brian Anand, Inder Rossignol, Patrick Desai, Akshay S Zannad, Faiez Pitt, Bertram Solomon, Scott D |
| description | Mineralocorticoid receptor antagonists reduce morbidity and mortality in patients with heart failure but can cause hyperkalemia, which contributes to reduced use of these drugs. Hypokalemia also leads to worse outcomes in patients with heart failure and may be attenuated by mineralocorticoid receptor antagonists.
We assessed incidence and predictors of hyperkalemia (potassium ≥5.5 mmol/L) and hypokalemia (potassium |
| doi_str_mv | 10.1161/CIRCHEARTFAILURE.114.001104 |
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We assessed incidence and predictors of hyperkalemia (potassium ≥5.5 mmol/L) and hypokalemia (potassium <3.5 mmol/L) and the relationship to outcomes in 1663 patients with class III or IV heart failure and left ventricular ejection fraction <35% randomized to treatment with spironolactone 25 mg or placebo in the Randomized Aldactone Evaluation Study (RALES) trial. All-cause mortality rates and the influence of potassium levels on the effectiveness of spironolactone were assessed in a landmark analysis and in relation to time-varying potassium levels. After 1 month, mean potassium levels increased in the spironolactone group but not in the placebo group (4.54±0.49 versus 4.28±0.50 mmol/L; P<0.001) and remained elevated during the trial. Although the extremes of hypokalemia and hyperkalemia at 4 weeks were associated with increased risk of mortality in both treatment arms, participants in the spironolactone arm had lower mortality rates at all potassium levels throughout the duration of the trial. The treatment benefit of spironolactone was maintained at least until potassium exceeded 5.5 mmol/L.
With appropriate surveillance of potassium and creatinine, the use of spironolactone was associated with less hypokalemia and improved survival in patients with severe heart failure even in the setting of moderate hyperkalemia.</description><identifier>ISSN: 1941-3289</identifier><identifier>EISSN: 1941-3297</identifier><identifier>DOI: 10.1161/CIRCHEARTFAILURE.114.001104</identifier><identifier>PMID: 24812304</identifier><language>eng</language><publisher>United States</publisher><subject>Cause of Death - trends ; Dose-Response Relationship, Drug ; Double-Blind Method ; Echocardiography ; Follow-Up Studies ; Global Health ; Heart Failure - diagnostic imaging ; Heart Failure - drug therapy ; Heart Failure - mortality ; Heart Ventricles - diagnostic imaging ; Heart Ventricles - physiopathology ; Hyperkalemia - blood ; Hyperkalemia - chemically induced ; Hyperkalemia - epidemiology ; Hypokalemia - blood ; Hypokalemia - chemically induced ; Hypokalemia - epidemiology ; Incidence ; Mineralocorticoid Receptor Antagonists - administration & dosage ; Mineralocorticoid Receptor Antagonists - adverse effects ; Potassium - blood ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Spironolactone - administration & dosage ; Spironolactone - adverse effects ; Stroke Volume ; Survival Rate - trends ; Treatment Outcome ; Ventricular Function, Left - drug effects</subject><ispartof>Circulation. Heart failure, 2014-07, Vol.7 (4), p.573-579</ispartof><rights>2014 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-bf526db0123008ec48c7693eed19633fd7959b122fdf8aa19c89e665f9355a733</citedby><cites>FETCH-LOGICAL-c374t-bf526db0123008ec48c7693eed19633fd7959b122fdf8aa19c89e665f9355a733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24812304$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vardeny, Orly</creatorcontrib><creatorcontrib>Claggett, Brian</creatorcontrib><creatorcontrib>Anand, Inder</creatorcontrib><creatorcontrib>Rossignol, Patrick</creatorcontrib><creatorcontrib>Desai, Akshay S</creatorcontrib><creatorcontrib>Zannad, Faiez</creatorcontrib><creatorcontrib>Pitt, Bertram</creatorcontrib><creatorcontrib>Solomon, Scott D</creatorcontrib><creatorcontrib>Randomized Aldactone Evaluation Study (RALES) Investigators</creatorcontrib><title>Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist</title><title>Circulation. Heart failure</title><addtitle>Circ Heart Fail</addtitle><description>Mineralocorticoid receptor antagonists reduce morbidity and mortality in patients with heart failure but can cause hyperkalemia, which contributes to reduced use of these drugs. Hypokalemia also leads to worse outcomes in patients with heart failure and may be attenuated by mineralocorticoid receptor antagonists.
We assessed incidence and predictors of hyperkalemia (potassium ≥5.5 mmol/L) and hypokalemia (potassium <3.5 mmol/L) and the relationship to outcomes in 1663 patients with class III or IV heart failure and left ventricular ejection fraction <35% randomized to treatment with spironolactone 25 mg or placebo in the Randomized Aldactone Evaluation Study (RALES) trial. All-cause mortality rates and the influence of potassium levels on the effectiveness of spironolactone were assessed in a landmark analysis and in relation to time-varying potassium levels. After 1 month, mean potassium levels increased in the spironolactone group but not in the placebo group (4.54±0.49 versus 4.28±0.50 mmol/L; P<0.001) and remained elevated during the trial. Although the extremes of hypokalemia and hyperkalemia at 4 weeks were associated with increased risk of mortality in both treatment arms, participants in the spironolactone arm had lower mortality rates at all potassium levels throughout the duration of the trial. The treatment benefit of spironolactone was maintained at least until potassium exceeded 5.5 mmol/L.
With appropriate surveillance of potassium and creatinine, the use of spironolactone was associated with less hypokalemia and improved survival in patients with severe heart failure even in the setting of moderate hyperkalemia.</description><subject>Cause of Death - trends</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Echocardiography</subject><subject>Follow-Up Studies</subject><subject>Global Health</subject><subject>Heart Failure - diagnostic imaging</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - mortality</subject><subject>Heart Ventricles - diagnostic imaging</subject><subject>Heart Ventricles - physiopathology</subject><subject>Hyperkalemia - blood</subject><subject>Hyperkalemia - chemically induced</subject><subject>Hyperkalemia - epidemiology</subject><subject>Hypokalemia - blood</subject><subject>Hypokalemia - chemically induced</subject><subject>Hypokalemia - epidemiology</subject><subject>Incidence</subject><subject>Mineralocorticoid Receptor Antagonists - administration & dosage</subject><subject>Mineralocorticoid Receptor Antagonists - adverse effects</subject><subject>Potassium - blood</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Severity of Illness Index</subject><subject>Spironolactone - administration & dosage</subject><subject>Spironolactone - adverse effects</subject><subject>Stroke Volume</subject><subject>Survival Rate - trends</subject><subject>Treatment Outcome</subject><subject>Ventricular Function, Left - drug effects</subject><issn>1941-3289</issn><issn>1941-3297</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUctO6zAQtRCI9y8gS2xYELBjO4nFqqoKVKqEVME6cu0JNSRxsJ17xd_wqZgWWLCa15lzZnQQOqfkitKCXk_ny-n9bLJ8vJ3MF0_LWeryK0IoJXwHHVLJacZyWe7-5pU8QEchvBBS5ELIfXSQ84rmjPBD9DHvtTXQa7jEgwdjdXQ-XGLVG-zGqF0HAXtoVQSDo8Pr98Flm2nKwL-qFjqrsO3xoKKFPgb838Y1DvAPPOA1KB9xo2w7pip62PBsEAp3tgevWqedj1Y7a5KQhiEdkASiena9DfEE7TWqDXD6HY_R0-3scXqfLR7u5tPJItOs5DFbNSIvzIp8vUUq0LzSZSEZgKGyYKwxpRRyRfO8MU2lFJW6klAUopFMCFUydowutryDd28jhFh3NmhoW9WDG0NNBRdlKcpKJOjNFqq9C8FDUw_edsq_15TUXxbVfy1KXV5vLUrbZ99C46oD87v74wn7BOXmksU</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Vardeny, Orly</creator><creator>Claggett, Brian</creator><creator>Anand, Inder</creator><creator>Rossignol, Patrick</creator><creator>Desai, Akshay S</creator><creator>Zannad, Faiez</creator><creator>Pitt, Bertram</creator><creator>Solomon, Scott D</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201407</creationdate><title>Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist</title><author>Vardeny, Orly ; Claggett, Brian ; Anand, Inder ; Rossignol, Patrick ; Desai, Akshay S ; Zannad, Faiez ; Pitt, Bertram ; Solomon, Scott D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-bf526db0123008ec48c7693eed19633fd7959b122fdf8aa19c89e665f9355a733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Cause of Death - trends</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Echocardiography</topic><topic>Follow-Up Studies</topic><topic>Global Health</topic><topic>Heart Failure - diagnostic imaging</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - mortality</topic><topic>Heart Ventricles - diagnostic imaging</topic><topic>Heart Ventricles - physiopathology</topic><topic>Hyperkalemia - blood</topic><topic>Hyperkalemia - chemically induced</topic><topic>Hyperkalemia - epidemiology</topic><topic>Hypokalemia - blood</topic><topic>Hypokalemia - chemically induced</topic><topic>Hypokalemia - epidemiology</topic><topic>Incidence</topic><topic>Mineralocorticoid Receptor Antagonists - administration & dosage</topic><topic>Mineralocorticoid Receptor Antagonists - adverse effects</topic><topic>Potassium - blood</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Severity of Illness Index</topic><topic>Spironolactone - administration & dosage</topic><topic>Spironolactone - adverse effects</topic><topic>Stroke Volume</topic><topic>Survival Rate - trends</topic><topic>Treatment Outcome</topic><topic>Ventricular Function, Left - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vardeny, Orly</creatorcontrib><creatorcontrib>Claggett, Brian</creatorcontrib><creatorcontrib>Anand, Inder</creatorcontrib><creatorcontrib>Rossignol, Patrick</creatorcontrib><creatorcontrib>Desai, Akshay S</creatorcontrib><creatorcontrib>Zannad, Faiez</creatorcontrib><creatorcontrib>Pitt, Bertram</creatorcontrib><creatorcontrib>Solomon, Scott D</creatorcontrib><creatorcontrib>Randomized Aldactone Evaluation Study (RALES) Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation. Heart failure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vardeny, Orly</au><au>Claggett, Brian</au><au>Anand, Inder</au><au>Rossignol, Patrick</au><au>Desai, Akshay S</au><au>Zannad, Faiez</au><au>Pitt, Bertram</au><au>Solomon, Scott D</au><aucorp>Randomized Aldactone Evaluation Study (RALES) Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist</atitle><jtitle>Circulation. Heart failure</jtitle><addtitle>Circ Heart Fail</addtitle><date>2014-07</date><risdate>2014</risdate><volume>7</volume><issue>4</issue><spage>573</spage><epage>579</epage><pages>573-579</pages><issn>1941-3289</issn><eissn>1941-3297</eissn><abstract>Mineralocorticoid receptor antagonists reduce morbidity and mortality in patients with heart failure but can cause hyperkalemia, which contributes to reduced use of these drugs. Hypokalemia also leads to worse outcomes in patients with heart failure and may be attenuated by mineralocorticoid receptor antagonists.
We assessed incidence and predictors of hyperkalemia (potassium ≥5.5 mmol/L) and hypokalemia (potassium <3.5 mmol/L) and the relationship to outcomes in 1663 patients with class III or IV heart failure and left ventricular ejection fraction <35% randomized to treatment with spironolactone 25 mg or placebo in the Randomized Aldactone Evaluation Study (RALES) trial. All-cause mortality rates and the influence of potassium levels on the effectiveness of spironolactone were assessed in a landmark analysis and in relation to time-varying potassium levels. After 1 month, mean potassium levels increased in the spironolactone group but not in the placebo group (4.54±0.49 versus 4.28±0.50 mmol/L; P<0.001) and remained elevated during the trial. Although the extremes of hypokalemia and hyperkalemia at 4 weeks were associated with increased risk of mortality in both treatment arms, participants in the spironolactone arm had lower mortality rates at all potassium levels throughout the duration of the trial. The treatment benefit of spironolactone was maintained at least until potassium exceeded 5.5 mmol/L.
With appropriate surveillance of potassium and creatinine, the use of spironolactone was associated with less hypokalemia and improved survival in patients with severe heart failure even in the setting of moderate hyperkalemia.</abstract><cop>United States</cop><pmid>24812304</pmid><doi>10.1161/CIRCHEARTFAILURE.114.001104</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1941-3289 |
| ispartof | Circulation. Heart failure, 2014-07, Vol.7 (4), p.573-579 |
| issn | 1941-3289 1941-3297 |
| language | eng |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Cause of Death - trends Dose-Response Relationship, Drug Double-Blind Method Echocardiography Follow-Up Studies Global Health Heart Failure - diagnostic imaging Heart Failure - drug therapy Heart Failure - mortality Heart Ventricles - diagnostic imaging Heart Ventricles - physiopathology Hyperkalemia - blood Hyperkalemia - chemically induced Hyperkalemia - epidemiology Hypokalemia - blood Hypokalemia - chemically induced Hypokalemia - epidemiology Incidence Mineralocorticoid Receptor Antagonists - administration & dosage Mineralocorticoid Receptor Antagonists - adverse effects Potassium - blood Retrospective Studies Risk Factors Severity of Illness Index Spironolactone - administration & dosage Spironolactone - adverse effects Stroke Volume Survival Rate - trends Treatment Outcome Ventricular Function, Left - drug effects |
| title | Incidence, predictors, and outcomes related to hypo- and hyperkalemia in patients with severe heart failure treated with a mineralocorticoid receptor antagonist |
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