Chlorothiazide Versus Metolazone in Hospitalized Patients with Heart Failure Receiving Loop Diruetics Barry Nicholson, PharmD; Halley Gibson, PharmD, BCPS Lahey Hospital & Medical Center, Burlington, MA

Background Baseline Characteristics Secondary Outcomes Results • Heart failure (HF) is the primary diagnosis in > 1 million hospitalizations annually Characteristic Metolazone Chlorothiazide p-value • Loop diuretics are first-line treatment for edema for most patients with HF, and Secondary Outcome Metolazone Chlorothiazide p-value (n=62) (n=59) thiazide diuretics may be used as an adjuvant option for additional diuresis1 (n=62) (n=59)

• Previous trials have shown that oral metolazone is non-inferior to intravenous chlorothiazide with regards to safety and efficacy2,3 Age (years) ± SD 75.6 ± 12.1 74.8 ± 12.1 0.55 Hypokalemia within 24 hours 13 (21) 14 (23.7) 0.89 • There is currently no institution-specific policy to guide thiazide diuretic post-thiazide, n (%) Male, n (%) 40 (64.5) 34 (56.7) 0.55 selection in patients with heart failure at Lahey Hospital & Medical Center Hypokalemia within 72 hours 10 (16.1) 5 (8.5) 0.32 post-thiazide, n (%) Objective Weight (kg) ± SD 92 ± 32.8 95.5 ± 31.1 0.54 To evaluate the safety and efficacy of chlorothiazide versus metolazone for Hypomagnesemia within 24 hours 5 (8.1) 7 (11.9) 0.69 Non-ICU, n (%) 48 (77.4) 39 (65) 0.24 augmented diuresis in hospitalized heart failure patients receiving loop diuretics post-thiazide, n (%) Endpoints Progressive Care Unit, n (%) 12 (19.4) 3 (5.1) 0.07 Hypomagnesemia within 72 hours 9 (14.5) 6 (10.2) 0.66 post-thiazide, n (%) Primary Endpoint Change in net urine output (UOP) pre and post-initiation Intensive Care Unit, n (%) 2 (3.2) 17 (28.8) <0.01* of either study thiazide diuretic at 24 and 72 hours Length of Stay, days ± SD 14.7 ± 6.6 17 ± 11.8 0.2 Serum creatinine, mg/dL ± SD 2.2 ± 1.2 2.2 ± 1.1 0.91 Secondary Endpoints - Incidence of the following at 24 and 72 hours: # patients needing additional 27 (43.5) 37 (62.7) 0.05 1. Electrolyte abnormalities thiazide diuretic doses, n (%) 2. Hypotension Potassium, mEq/L ± SD 4.2 ± 0.8 4.1 ± 0.75 0.48 3. Acute kidney injury * p < 0.05 indicates statistical significance Magnesium, mg/dL ± SD 2.1 ± 0.3 2 ± 0.44 0.14 - Inotrope administered within 24 hours Conclusions - Progression to renal replacement therapy Furosemide dose equivalent within 360.6 ± 225.9 476.4 ± 305.1 0.02* 59% ● Both metolazone and chlorothiazide were found to be comparable with respect - Hospital length of stay 24 hours pre-thiazide, mg ± SD 43% - Number of patients needing additional thiazide doses to providing additional diuresis to heart failure patients who were already * p < 0.05 indicates31% statistical significance receiving loop diuretics Methods ● There was no significant differences in rates of adverse effects between patients Primary Efficacy Results in the metolazone and chlorothiazide groups • Retrospective chart review conducted from August, 2018 - February, 2020 • Descriptive statistics were calculated as mean ± standard deviation and were Limitations compared using two-sided independent t-tests, or Χ2, as appropriate • 51 patients needed in each study arm to detect a 500-mL difference in UOP ● Patients were able to receive ● More patients in the chlorothiazide ○ ɑ = 0.05, power of 80%, p < 0.05 indicates statistical significance subsequent doses of diuretics group required subsequent dosing ● Majority of ICU patients in ● Unbalanced loop diuretic dosing Inclusion Criteria Exclusion Criteria chlorothiazide group ● Retrospective, single center study •- Admitted patients ≥ 18 years old - Intubated at the time of first dose - Diagnosis of HF - History of a kidney transplant Future Directions - Loop diuretic given within 24 hours - Renal replacement therapy needed of either metolazone or prior to thiazide initiation Results will be shared with members of the Cardiology and Heart Failure divisions chlorothiazide initiation - Received initial doses of both with discussion to potentially risk-stratify use of metolazone to preferential use - Fluid intake and UOP data measured metolazone and chlorothiazide in non-ICU patients at least 24 hours before and 72 within 24 hours of each other Disclosures hours after thiazide administration * p < 0.05 indicates statistical significance Authors of this presentation have no financial disclosure or conflicts of interest References 1. Guideline for the Management of Heart Failure AHA 2013. 2. Moranville, M et. al Cardiovascular Therapeutics; 2015 3. Schulenberger, C et. al Pharmacotherapy; 2016 with the presented material.