{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:13:08Z","timestamp":1789445588498,"version":"build-2803163510"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,9,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high\u2010dose loop diuretics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Patients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity\u2010adjusted analysis of all\u2010cause mortality. Secondary outcomes included hyponatremia (sodium &lt;135\n                      <jats:styled-content style=\"fixed-case\">mE<\/jats:styled-content>\n                      q\/L), hypokalemia (potassium &lt;3.5\n                      <jats:styled-content style=\"fixed-case\">mE<\/jats:styled-content>\n                      q\/L) and worsening renal function (a \u226520% decrease in estimated glomerular filtration rate). Of 13\u00a0898 admissions, 1048 (7.5%) used adjuvant metolazone. Metolazone was strongly associated with hyponatremia, hypokalemia, and worsening renal function (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001 for all) with minimal effect attenuation following covariate and propensity adjustment. Metolazone remained associated with increased mortality after multivariate and propensity adjustment (hazard ratio=1.20, 95% confidence interval 1.04\u20131.39,\n                      <jats:italic>P<\/jats:italic>\n                      =0.01). High\u2010dose loop diuretics were associated with hypokalemia and hyponatremia (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.002) but only worsening renal function retained significance (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001) after propensity adjustment. High\u2010dose loop diuretics were not associated with reduced survival after multivariate and propensity adjustment (hazard ratio=0.97 per 100\u00a0mg of IV furosemide, 95% confidence interval 0.90\u20131.06,\n                      <jats:italic>P<\/jats:italic>\n                      =0.52).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">During acute decompensated heart failure, metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function and increased mortality after controlling for the propensity to receive metolazone and baseline characteristics. However, under the same experimental conditions, high\u2010dose loop diuretics were not associated with hypokalemia, hyponatremia, or reduced survival. The current findings suggest that until randomized control trial data prove otherwise, uptitration of loop diuretics may be a preferred strategy over routine early addition of thiazide type diuretics when diuresis is inadequate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.118.009149","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T11:02:17Z","timestamp":1537095737000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Outcomes Associated With a Strategy of Adjuvant Metolazone or High\u2010Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis"],"prefix":"10.1161","volume":"7","author":[{"given":"Meredith A.","family":"Brisco\u2010Bacik","sequence":"first","affiliation":[{"name":"Divisions of Cardiology and Cardiovascular Research Lewis Katz School of Medicine at Temple University Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozine M.","family":"ter Maaten","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Houser","sequence":"additional","affiliation":[{"name":"Divisions of Cardiology and Cardiovascular Research Lewis Katz School of Medicine at Temple University Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha A.","family":"Vedage","sequence":"additional","affiliation":[{"name":"Divisions of Cardiology and Cardiovascular Research Lewis Katz School of Medicine at Temple University Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine New Haven CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Section\u00a0of Cardiovascular Medicine Yale University School of Medicine New Haven CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Perry","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine New Haven CT"},{"name":"Clinical Epidemiology Research Center Veterans Affairs Medical Center New Haven CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Testani","sequence":"additional","affiliation":[{"name":"Section\u00a0of Cardiovascular Medicine Yale University School of Medicine New Haven CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2004.08.005"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2006.09.011"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000895"},{"key":"e_1_3_1_5_2","first-page":"e240","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"62","author":"Yancy CW","year":"2013","unstructured":"Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation and American Heart Association Task Force on Practice Guidelines . 2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines. 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