085 - Oral Metolazone Increases Urine Output Comparable to Chlorothiazide IV as an Adjunct to Loop Diuretics in HFrEF Patients with ADHF

Thiazide diuretics are often utilized to overcome loop diuretic resistance when treating ADHF. In addition to a large cost advantage, several pharmacokinetic advantages exist when administering oral metolazone (MT) compared to IV chlorothiazide (CT); yet many providers are reluctant to utilize an oral formulation to treat ADHF. Several studies have found no difference in efficacy between the agents, however these studies had limited patients, utilized net UOP which can be misleading if patients are intubated or fluid restricted, and included HFpEF patients which may not have comparable UOP goals to HFrEF patients. The purpose of this study was to compare the increase in 24 hr total UOP after adding MT or CT to IV loop diuretics (LD) in patients with HFrEF. This was an IRB-approved, single-center retrospective chart review. Inclusion criteria were EF ≤40% and >24 hr use of LD with recorded UOP prior to administration of MT ≥ 5 mg or CT ≥ 500 mg. Patients with dialysis, no oral or per tube medications within 24 hr, or an overlap of MT/CT therapy were excluded. Baseline characteristics and safety data were collected in addition to 24 hr UOP prior and post drug administration. A subgroup analysis of patients receiving vasopressors was conducted a priori. From 9/2013-8/2016, 961 patients received either MT or CT in addition to LD. Most patients were excluded for HFpEF (n = 469), < 24 hr LD or UOP data prior to drug initiation (n = 129), or low dose MT/CT (n = 91). A total of 168 patients were included with 64% receiving CT. Baseline characteristics are listed in Table 1. No significant difference was observed between the increase in 24 hr total UOP after MT or CT initiation (1458 (514,2401) mL v. 1820 (890,2750) mL, P = .251). Net UOP and UOP for the entire course of MT or CT therapy are displayed in Figure. Additionally the vasopressor subgroup analysis (MT n = 16, CT n = 34) revealed no difference in increase in UOP between agents (1622 (60,3186) mL v. 1865 (302,3428) mL, P = .506). Both MT and CT similarly increased UOP when utilized as an adjunct to IV loop diuretics. These results may suggest that while thiazide agents can substantially increase UOP in ADHF patients with rEF and diuretic resistance, IV chlorothiazide may not offer benefit beyond oral metolazone 5 mg. A prospective RCT would be necessary to confirm.Table 1Baseline Characteristics for HFrEF Utilizing Thiazides for ADHF with Loop ResistanceBaseline CharacteristicIV Chlorothiazide (n = 108)Oral Metolazone (n = 60)PAge, yr64 (54,69)63 (54,74).558Male Sex, n(%)74 (69)41 (68).98White Race, n(%)68 (63)34 (57).621EF, %22 (15,30)23 (17,30).293BNP, pg/mL1371 (830,2230)1517 (825,3313).620SCr, mg/dL1.5 (1.0,2.1)1.6 (1.2,2.1).328cCrCl, mL/min47 (30,68)43 (30,61).390Total UOP, mL1693 (863,2388)1675 (1113,2591).330Net UOP, mL-350 (±1217)-552 (±1205).303Hospital LOS, days16 (9,28)13 (8,32).502Loop Continuous Infusion, n(%)67 (62)25 (42).011IV Inotropes, n(%)53 (49)24 (40).258ICU, n(%)77 (71)38 (63).287ICU LOS, days4 (0,10)2 (0,8).088Vasopressor, n(%)34 (32)16 (27).892Mechanical Ventilation, n(%)15 (14)2 (3).033APACHE II, score12 (9,15)10 (7,14).099Inhospital Morality, n(%)21 (19)1 (2).001 Open table in a new tab