The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jeffrey M. Testani - One of the best experts on this subject based on the ideXlab platform.
-
Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial
JACC. Heart failure, 2019Co-Authors: Zachary L Cox, Rebecca Hung, Daniel J. Lenihan, Jeffrey M. TestaniAbstract:Abstract Objectives This study compared combination diuretic strategies in acute heart failure (AHF) complicated by diuretic resistance (DR). Background Combination diuretic regimens to overcome loop DR are commonly used but with limited evidence. Methods This study was a randomized, double-blinded trial in 60 patients hospitalized with AHF and intravenous (IV) loop DR. Patients were randomized to oral Metolazone, IV chlorothiazide, or tolvaptan therapy. All patients received concomitant high-dose IV infusions of furosemide. The primary outcome was 48-h weight loss. Results The cohort exhibited DR prior to enrollment, producing 1,188 ± 476 ml of urine in 12 h during high-dose loop diuretic therapy (IV furosemide: 612 ± 439 mg/day). All 3 interventions significantly improved diuretic efficacy (p Conclusions In this moderately sized DR trial, weight loss was excellent with the addition of Metolazone, IV chlorothiazide, or tolvaptan to loop diuretics, without a detectable between-group difference. (Comparison of Oral or Intravenous Thiazides vs. tolvaptan in Diuretic Resistant Decompensated Heart Failure [3T]; NCT02606253)
-
Efficacy of Intravenous Chlorothiazide for Refractory Acute Decompensated Heart Failure Unresponsive to Adjunct Metolazone
Pharmacotherapy, 2016Co-Authors: Maria Cardinale, Jerry Altshuler, Jeffrey M. TestaniAbstract:tudy Objective To assess the efficacy of intravenous chlorothiazide in patients with acute decompensated heart failure (ADHF) who were determined to be loop diuretic resistant and refractory to Metolazone. Design Retrospective cohort study with patients serving as their own controls. Setting Large, academic, tertiary care hospital. Patients Forty-five patients with ADHF who had an inadequate response to high-dose loop diuretics and then received at least one dose of oral Metolazone 5 mg or greater (Metolazone index dose) followed by at least one dose of intravenous chlorothiazide 500 mg (chlorothiazide index dose) if the response to Metolazone was considered inadequate, according to the institutional protocol, between February 4, 2013, and February 28, 2015, were included. If multiple doses of Metolazone were administered, the last dose given before the chlorothiazide index dose was considered the index dose; the Metolazone index dose had to have been administered more than 2 hours before the chlorothiazide index dose. Measurements and Main Results Data for a total of 90 diuretic doses (45 Metolazone, 45 chlorothiazide) were included in the analysis. The median dose of loop diuretic in intravenous furosemide equivalents given over the 24-hour period before the Metolazone index dose was 400 mg. The average length of stay was 34.7 days, and in-hospital mortality was 35.6% (16/45 patients). The primary end point of a net-negative urine output of 500 ml or greater during the 12 hours after the index dose occurred in 42.2% (19/45 patients) and 35.5% (16/45 patients) for the chlorothiazide and Metolazone doses, respectively (p=0.581). The median 12-hour urine output following administration of Metolazone was 810 ml (interquartile range [IQR] 866 ml) versus 1075 ml (IQR 940 ml) following administration of chlorothiazide (p=0.363). Compared with Metolazone, the chlorothiazide doses did not result in an increase in urine output of at least 500 ml during the 12 hours following the dose relative to the 12 hours before the dose (31.1% vs 22.2%, p=0.754). No significant difference in achievement of net-negative urine output of 500 ml or greater during the 12 hours following the chlorothiazide or Metolazone dose was noted (42.2% for chlorothiazide vs 35.5% for Metolazone, p=0.581). Conclusion The addition of intravenous chlorothiazide did not result in improved diuresis in patients with ADHF determined to be refractory to loop diuretics and adjunctive oral Metolazone.
Brent N Reed - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of intravenous chlorothiazide versus oral Metolazone in patients with acute decompensated heart failure and loop diuretic resistance
Pharmacotherapy, 2016Co-Authors: Christine E Shulenberger, Anthony Jiang, Sandeep Devabhakthuni, Vijay Ivaturi, Tao Liu, Brent N ReedAbstract:tudy Objective 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 (ADHF) and loop diuretic resistance. Design Retrospective cohort study. Setting Large urban academic medical center. Patients Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/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. Measurements and Main Results The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type 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-type diuretic administration) was higher in the chlorothiazide group (mean ± SD 318.9 ± 127.7 vs 268.4 ± 97.6 mg/day in the Metolazone group, p=0.004), but net UOP was similar (mean ± SD 877.0 ± 1189.0 ml in the chlorothiazide group vs 710.6 ± 1145.9 ml in the Metolazone group, p=0.344). Mean doses of chlorothiazide and Metolazone were 491 ± 282 mg and 5.8 ± 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 ± 1443.0 ml vs 2030.2 ± 1725.0 ml 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 ± 1517.4 ml versus 1397.6 ± 1370.7 ml 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. Conclusion Oral Metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF 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-line option in this patient population.
Taylor D Steuber - One of the best experts on this subject based on the ideXlab platform.
-
a systematic review and meta analysis of Metolazone compared to chlorothiazide for treatment of acute decompensated heart failure
Pharmacotherapy, 2020Co-Authors: Taylor D Steuber, Kristin M Janzen, Meredith L HowardAbstract: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-type diuretic; however, it is unknown which thiazide-type diuretic used in this setting is most effective. A systematic review and meta-analysis were performed to compare the efficacy and safety of chlorothiazide with Metolazone as add-on 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-language 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 hours in patients with ADHF. Meta-analysis was conducted to evaluate pooled effect size by using a random-effect 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-on to loop diuretics in treating ADHF without an increase in safety concerns.
Jonathan D. Rich - One of the best experts on this subject based on the ideXlab platform.
-
Comparison of Metolazone Versus Chlorothiazide in Acute Decompensated Heart Failure with Diuretic Resistance
Cardiovascular therapeutics, 2015Co-Authors: Michael P. Moranville, Suji Choi, Jennifer Hogg, Allen S. Anderson, Jonathan D. RichAbstract:SummaryAims Sequential nephron blockade with thiazide-like diuretics is a strategy used to overcome diuretic resistance in acute decompensated heart failure (ADHF), but head-to-head studies are lacking and equipoise exists regarding the preferred thiazide-like diuretic in this setting. We thus compared the effectiveness of oral Metolazone versus intravenous (IV) chlorothiazide as add-on therapy to loop diuretics in hospitalized patients with ADHF and renal dysfunction. Methods This retrospective cohort study evaluated the efficacy and safety of oral Metolazone versus IV chlorothiazide as add-on therapy to loop diuretics in patients hospitalized with ADHF and renal dysfunction. The primary endpoint was net urine output (UOP) at 72 h after initiation of thiazide-like diuretics. Safety endpoints included worsening renal function, hypotension, and electrolyte abnormalities. Results Fifty-five patients were enrolled with 33 patients receiving Metolazone and 22 patients receiving chlorothiazide. There was no difference in median net UOP at 72 h in those receiving Metolazone (4828 mL, interquartile range [IQR] 2800–7209 mL) compared to chlorothiazide (3779 mL, IQR 1885–6535 mL) (P = 0.16). There was no difference in hypotension, worsening renal function, hyponatremia, or hypokalemia (P = NS for all comparisons). Hospital length of stay was shorter in the Metolazone cohort (median 7 days) compared to chlorothiazide (median 15 days), suggesting the chlorothiazide cohort was likely sicker. Conclusion Sequential nephron blockade with either Metolazone or chlorothiazide appears to be efficacious and safe in ADHF, renal dysfunction, and diuretic resistance. Given the considerable cost difference favoring oral Metolazone, larger randomized studies are warranted to confirm our findings and to exclude the possibility of confounding by indication.
Sandeep Devabhakthuni - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of intravenous chlorothiazide versus oral Metolazone in patients with acute decompensated heart failure and loop diuretic resistance
Pharmacotherapy, 2016Co-Authors: Christine E Shulenberger, Anthony Jiang, Sandeep Devabhakthuni, Vijay Ivaturi, Tao Liu, Brent N ReedAbstract:tudy Objective 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 (ADHF) and loop diuretic resistance. Design Retrospective cohort study. Setting Large urban academic medical center. Patients Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/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. Measurements and Main Results The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type 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-type diuretic administration) was higher in the chlorothiazide group (mean ± SD 318.9 ± 127.7 vs 268.4 ± 97.6 mg/day in the Metolazone group, p=0.004), but net UOP was similar (mean ± SD 877.0 ± 1189.0 ml in the chlorothiazide group vs 710.6 ± 1145.9 ml in the Metolazone group, p=0.344). Mean doses of chlorothiazide and Metolazone were 491 ± 282 mg and 5.8 ± 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 ± 1443.0 ml vs 2030.2 ± 1725.0 ml 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 ± 1517.4 ml versus 1397.6 ± 1370.7 ml 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. Conclusion Oral Metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF 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-line option in this patient population.