{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:18:27Z","timestamp":1789039107519,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"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":[[2020,9]]},"abstract":"<jats:p>Treatment of volume overload in the setting of acute decompensated heart failure (ADHF) is typically achieved through the use of loop diuretics. While they are highly effective, some patients may develop loop diuretic resistance. One strategy to overcome this scenario includes sequential nephron blockade with a thiazide\u2010type diuretic; however, it is unknown which thiazide\u2010type diuretic used in this setting is most effective. A systematic review and meta\u2010analysis were performed to compare the efficacy and safety of chlorothiazide with metolazone as add\u2010on therapy in the setting of loop diuretic resistance for the treatment of ADHF. Literature searches were conducted through PubMed, Google Scholar, and Science Direct from inception through February 2020 using the following search terms alone or in combination: metolazone, chlorothiazide, acute decompensated heart failure, loop diuretic, and urine output. All English\u2010language prospective and retrospective trials and abstracts comparing metolazone to chlorothiazide for the treatment of ADHF were evaluated. Studies were included if they analyzed urine output for at least 24\u00a0hours in patients with ADHF. Meta\u2010analysis was conducted to evaluate pooled effect size by using a random\u2010effect model. Primary outcomes included net and total urine output. Secondary outcomes included commonly reported safety outcomes. Four studies comparing the use of metolazone to chlorothiazide as an adjunct to loop diuretics to treat ADHF were included in the evaluation. Metolazone was as effective as chlorothiazide to augment loop diuretic therapy in ADHF in most studies with no pooled difference in net or total urine output. However, there were notable differences in baseline loop diuretic dosing, ejection fraction, renal function, race, and endpoint timing across studies. Adverse effects were commonly observed and included electrolyte abnormalities, change in renal function, and hypotension but were comparable between groups. Metolazone is as effective as chlorothiazide as add\u2010on to loop diuretics in treating ADHF without an increase in safety concerns.<\/jats:p>","DOI":"10.1002\/phar.2440","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T10:54:27Z","timestamp":1594205667000},"page":"924-935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Systematic Review and Meta\u2010Analysis of Metolazone Compared to Chlorothiazide for Treatment of Acute Decompensated Heart Failure"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7656-1504","authenticated-orcid":false,"given":"Taylor D.","family":"Steuber","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice Auburn University Harrison School of Pharmacy Huntsville Alabama USA"},{"name":"Department of Pharmacy Huntsville Hospital Huntsville Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8669-3527","authenticated-orcid":false,"given":"Kristin M.","family":"Janzen","sequence":"additional","affiliation":[{"name":"Division of Pharmacy Practice The University of Texas at Austin College of Pharmacy Austin Texas USA"},{"name":"Department of Pharmacy Dell Seton Medical Center at the University of Texas Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4514-3948","authenticated-orcid":false,"given":"Meredith L.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy University of North Texas System College of Pharmacy Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"240","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":"128","author":"Yancy CW","year":"2013","journal-title":"Circulation"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.06.034"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2016.08.027"},{"key":"e_1_2_7_5_1","unstructured":"Chlorothiazide [Package Insert].Schaumburg IL:Sagent Pharmaceuticals;2014."},{"key":"e_1_2_7_6_1","unstructured":"Metolazone [Package Insert].Morgantown WV:Mylan Pharmaceuticals Inc;2004."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630030-00004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1974162322"},{"key":"e_1_2_7_9_1","first-page":"134","article-title":"Treatment of furosemide resistant edema with metolazone","volume":"4","author":"Asscher AW","year":"1974","journal-title":"Clin Trials J"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2016.22.10.1107"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1755-5922.12109"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1798"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0018578718795855"},{"key":"e_1_2_7_14_1","article-title":"Diuretic strategies for loop diuretic resistance in acute heart failure: the 3T trial","author":"Cox ZL","year":"2019","journal-title":"JACC Heart Fail"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-019-09851-9"},{"key":"e_1_2_7_16_1","unstructured":"Prospective comparison of metolazone versus chlorothiazide for acute decompensated heart failure with diuretic resistance \u2013 ClinicalTrials.gov.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03574857. 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