Study Purpose: To identify change in loop diuretic dose when initiating a SGLT2i in patients with HFrEF who are on a stable dose of loop diuretic in the outpatient settinghttps://jdc.jefferson.edu/pharmacyposters/1025/thumbnail.jp

Karalis, MD, FACC, FNLA, D. G.

Mirachi, PA-C, N.

Thoma, PharmD, BCPS, BCCP, B.

Wildemann, PharmD, R.

English

Jefferson Digital Commons

Thomas Jefferson University Jefferson Digital Commons College of Pharmacy Posters Jefferson College of Pharmacy 4-2022 Change in Diuretic Dose after Initiation of a SGLT2 Inhibitor in Patients with Heart Failure with Reduced Ejection Fraction R. Wildemann, PharmD D. G. Karalis, MD, FACC, FNLA N. Mirachi, PA-C B. Thoma, PharmD, BCPS, BCCP Follow this and additional works at: https://jdc.jefferson.edu/pharmacyposters  Part of the Pharmacy and Pharmaceutical Sciences Commons Let us know how access to this document benefits you This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. 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Background• Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are the latest addition to medications that reduce mortality and morbidity in heart failure with reduced ejection fraction (HFrEF)• Dapagliflozin and empagliflozin are both FDA approved for patients with HFrEF regardless of concomitant type-2 diabetes mellitus• Multiple mechanisms have been proposed for the cardiovascular benefits of SGLT2i’s, including prevention of cardiac remodeling, blood pressure reduction, and improved cardiac energy metabolism• Inhibition of SGLT2 also causes an osmotic gradient between the glomerular circulation and urinary tubule leading to glucosuria, natriuresis, and diuresis• The quantity of SGLT2i associated diuresis has not been well defined leading to unclear needs for loop diuretic dose adjustment when initiating a SGLT2i • The RECEDE-CHF trial showed an approximately 500 mL increase in diuresis over a 24 hour-period after the addition of empagliflozin, but it was limited by a small population (n=23)MethodsChange in Diuretic Dose after Initiation of a SGLT2 Inhibitor in Patients with Heart Failure with Reduced Ejection FractionR. Wildemann, PharmD1; D. G. Karalis, MD, FACC, FNLA2; N. Mirachi, PA-C2, B. Thoma, PharmD, BCPS, BCCP1, R. D'Angelo, PharmD, BCPS31Department of Pharmacy, Thomas Jefferson University Hospital, Philadelphia, PA;2Cardiology Consultants of Philadelphia, Philadelphia, PA; 3Department of Pharmacy, University of Pennsylvania, Philadelphia, PA1. Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8):e254-e743.2. Yancy CW, Jessup M, Bozkurt B, et al. 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. J Am Coll Cardiol. 2013;62(16):e147-e239. doi:10.1016/j.jacc.2013.05.0193. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70(6):776-803. doi:10.1016/j.jacc.2017.04.0254. Fathi A, Vickneson K, Singh JS. SGLT2-inhibitors; more than just glycosuria and diuresis. Heart Fail Rev. 2021;26(3):623-642. doi:10.1007/s10741-020-10038-w5. Fitchett D, Inzucchi SE, Cannon CP, et al. Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial. Circulation. 2019;139(11):1384-1395. doi:10.1161/CIRCULATIONAHA.118.0377786. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. doi:10.1056/NEJMoa18123897. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa19113038. Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424. doi:10.1056/NEJMoa20221909. Mordi NA, Mordi IR, Singh JS, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure: The RECEDE-CHF Trial [published correction appears in Circulation. 2020 Nov 3;142(18):e316]. Circulation. 2020;142(18):1713-1724. doi:10.1161/CIRCULATIONAHA.120.048739LimitationsStatistical AnalysisStudy Purpose• To identify change in loop diuretic dose when initiating a SGLT2i in patients with HFrEF who are on a stable dose of loop diuretic in the outpatient settingOutcomesDisclosure: Authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation.• Primary Objective: • Secondary Objectives: Change in loop diuretic dose at 3 months post-SGLT2i initiationDose change in other diuretic medications, such as thiazide-like diuretics and mineralocorticoid receptor antagonists, at 3 months post-SGLT2i initiationThe patient’s HF status based on NYHA classification at 3 months post-SGLT2i initiationIncidence of adverse effects after SGLT2i initiation (change in serum creatinine, change in serum sodium, and UTI incidence)ResultsConclusions• Retrospective Chart Review• 01/01/2020 – 09/30/2021• Small, retrospective, two-center study• Only included outpatients initiated on a SGLT2i• Follow-up limited to approximately 3 monthsNominal DataContinuous DataChi-SquaredWilcoxon-Signed RankN (%)Median (IQR)182 patients screened who were initiated on a SGLT2i in the outpatient setting113 patients excluded69 patients included(57 dapagliflozin,12 empagliflozin)Data at SGLT2i initiationData at approximately 3-month follow-up visitBaseline Characteristics N = 69Age in years, median (IQR) 64(57.5-70.5)Male 48 (69.6)Race/EthnicityWhiteAfrican AmericanOther33 (47.8)30 (43.5)6 (8.6)Ejection Fraction, %, median (IQR)20(15-30)NYHA ClassificationIIIIIIIVUnknown7 (10.1)29 (42.0)26 (37.7)2 (2.9)5 (7.2)Ischemic heart failure etiology 20 (29.0)All data is n (%) unless noted otherwise.Home medications N = 69ACEI/ARB 12 (17.4)ARNI 51 (73.9)Beta Blocker 67 (97.1)Mineralocorticoid Receptor Antagonist 45 (65.2)Hydralazine/isosorbidedinitrate 4 (5.8)Digoxin 7 (10.1)Metolazone 2 (2.9)Chlorthalidone 0 (0)Hydrochlorothiazide 0 (0)Furosemide equivalents,mg, median (IQR)40.0(22.9, 80.0)All data is n (%) unless noted otherwise.Decreased, 26 patients 38%Increased, 3 patients, 4%No Change, 40 patients, 58%Loop Diuretic Dose Change at a Median of 94 daysFurosemide Equivalents Pre and Post SGLT2 InitiationNo significant differences in secondary outcomesP = 0.001Inclusion• Age ≥18 years old• EF ≤ 40%• Initiation of SGLT2i as outpatient• On a loop diuretic prior to SGLT2i initiationExclusion• eGFR <20 mL/min/1.73 m2 or dialysis• SGLT2i discontinued within 3 months of initiation• Insufficient data in patient’s chart or lack of follow-up• While the median loop diuretic dose was similar before and after SGLT2i initiation, there was a statistically significant number of patients who required loop diuretic dose reduction.• Initiation of a SGLT2i was not associated with a change in NYHA classification or a change in diuretic medications other than loop diuretics• SGLT2i’s were not associated with adverse effects such as change in serum creatinine, change in sodium, change in blood pressure, and urinary tract infections• When initiating a SGLT2i in a patient with HFrEF, it may be reasonable to consider an empiric loop diuretic dose reductionReferences

Change in Diuretic Dose after Initiation of a SGLT2 Inhibitor in Patients with Heart Failure with Reduced Ejection Fraction

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Change in Diuretic Dose after Initiation of a SGLT2 Inhibitor in Patients with Heart Failure with Reduced Ejection Fraction

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