{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:39:20Z","timestamp":1792291160413,"version":"4.4.0"},"reference-count":14,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,7,29]],"date-time":"2016-07-29T00:00:00Z","timestamp":1469750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>Study Objective<\/jats:title><jats:p>To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure (<jats:styled-content style=\"fixed-case\">ADHF<\/jats:styled-content>) and loop diuretic resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective cohort study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Large urban academic medical center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Adults admitted with <jats:styled-content style=\"fixed-case\">ADHF<\/jats:styled-content> between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160\u00a0mg\/day or higher (or an equivalent dose of IV bumetanide), during hospitalization, and who then received at least one dose of IV chlorothiazide (88 patients) or oral metolazone (89 patients) to augment diuresis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>The primary efficacy end point was a change in 24\u2010hour net urine output (UOP) from before to after thiazide\u2010type diuretic administration, and the study was designed to test for the noninferiority of metolazone. Safety end points included changes in renal function and electrolyte concentrations. The mean dose of IV loop diuretic therapy (in IV furosemide equivalents) at baseline (before thiazide\u2010type diuretic administration) was higher in the chlorothiazide group (mean\u00a0\u00b1\u00a0<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> 318.9\u00a0\u00b1\u00a0127.7 vs 268.4\u00a0\u00b1\u00a097.6\u00a0mg\/day in the metolazone group, p=0.004), but net UOP was similar (mean\u00a0\u00b1\u00a0<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> 877.0\u00a0\u00b1\u00a01189.0\u00a0ml in the chlorothiazide group vs 710.6\u00a0\u00b1\u00a01145.9\u00a0ml in the metolazone group, p=0.344). Mean doses of chlorothiazide and metolazone were 491\u00a0\u00b1\u00a0282\u00a0mg and 5.8\u00a0\u00b1\u00a03.5\u00a0mg, respectively. Following thiazide\u2010type diuretic administration, net UOP improved to a similar degree (2274.6\u00a0\u00b1\u00a01443.0\u00a0ml vs 2030.2\u00a0\u00b1\u00a01725.0\u00a0ml in the chlorothiazide and metolazone groups, respectively, p=0.308). For the primary efficacy end point, metolazone met the threshold for noninferiority by producing a net UOP of 1319.6\u00a0\u00b1\u00a01517.4\u00a0ml versus 1397.6\u00a0\u00b1\u00a01370.7\u00a0ml for chlorothiazide (p=0.026 for noninferiority). No significant differences in renal function were observed between the groups. Although hypokalemia was more frequent in the chlorothiazide group (75% with chlorothiazide vs 60.7% with metolazone, p=0.045), no significant differences in the rates of severe hypokalemia or other electrolyte abnormalities were observed between the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with <jats:styled-content style=\"fixed-case\">ADHF<\/jats:styled-content> and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities. Given the significant cost disparity between the two agents, these findings suggest that oral metolazone may be considered a first\u2010line option in this patient population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1798","type":"journal-article","created":{"date-parts":[[2016,7,9]],"date-time":"2016-07-09T03:22:56Z","timestamp":1468034576000},"page":"852-860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance"],"prefix":"10.1002","volume":"36","author":[{"given":"Christine E.","family":"Shulenberger","sequence":"first","affiliation":[{"name":"PinnacleHealth Harrisburg PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Jiang","sequence":"additional","affiliation":[{"name":"University of California Davis Medical Center Sacramento CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Devabhakthuni","sequence":"additional","affiliation":[{"name":"University of Maryland School of Pharmacy Baltimore MD"},{"name":"Applied Therapeutics, Research, and Instruction at the University of Maryland (ATRIUM) Cardiology Collaborative Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Ivaturi","sequence":"additional","affiliation":[{"name":"University of Maryland School of Pharmacy Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Maryland School of Pharmacy Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent N.","family":"Reed","sequence":"additional","affiliation":[{"name":"University of Maryland School of Pharmacy Baltimore MD"},{"name":"Applied Therapeutics, Research, and Instruction at the University of Maryland (ATRIUM) Cardiology Collaborative Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,29]]},"reference":[{"issue":"4","key":"e_1_2_6_2_1","first-page":"e29","article-title":"Heart disease and stroke statistics\u20142015 update: a report from the American Heart Association","volume":"131","author":"Mozaffarian D","year":"2015","journal-title":"Circulation"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.11.053"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/HHF.0b013e318291329a"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.05.019"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1005419"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2014.05.007"},{"key":"e_1_2_6_8_1","unstructured":"Red Book Online.Product Name Search. 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