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. 2023 Jul 1;8(7):652-661.
doi: 10.1001/jamacardio.2023.1266.

Contemporary Use of Sodium-Glucose Cotransporter-2 Inhibitor Therapy Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in the US: The Get With The Guidelines-Heart Failure Registry

Jacob B Pierce  1 , Muthiah Vaduganathan  2 , Gregg C Fonarow  3   4 , Uchechukwu Ikeaba  5 , Karen Chiswell  5 , Javed Butler  6   7 , Adam D DeVore  5   8 , Paul A Heidenreich  9 , Joanna C Huang  10 , Michelle M Kittleson  11 , Karen E Joynt Maddox  12 , Karthik K Linganathan  10 , James J McDermott  10 , Anjali Tiku Owens  13 , Pamela N Peterson  14   15 , Scott D Solomon  2 , Orly Vardeny  16 , Clyde W Yancy  17   18 , Stephen J Greene  5   8
Affiliations

Contemporary Use of Sodium-Glucose Cotransporter-2 Inhibitor Therapy Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in the US: The Get With The Guidelines-Heart Failure Registry

Jacob B Pierce et al. JAMA Cardiol. .

Abstract

Importance: Clinical guidelines for patients with heart failure with reduced ejection fraction (HFrEF) strongly recommend treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) to reduce cardiovascular mortality or HF hospitalization. Nationwide adoption of SGLT2i for HFrEF in the US is unknown.

Objective: To characterize patterns of SGLT2i use among eligible US patients hospitalized for HFrEF.

Design, setting, and participants: This retrospective cohort study analyzed 49 399 patients hospitalized for HFrEF across 489 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry between July 1, 2021, and June 30, 2022. Patients with an estimated glomerular filtration rate less than 20 mL/min/1.73 m2, type 1 diabetes, and previous intolerance to SGLT2i were excluded.

Main outcomes and measures: Patient-level and hospital-level prescription of SGLT2i at hospital discharge.

Results: Of 49 399 included patients, 16 548 (33.5%) were female, and the median (IQR) age was 67 (56-78) years. Overall, 9988 patients (20.2%) were prescribed an SGLT2i. SGLT2i prescription was less likely among patients with chronic kidney disease (CKD; 4550 of 24 437 [18.6%] vs 5438 of 24 962 [21.8%]; P < .001) but more likely among patients with type 2 diabetes (T2D; 5721 of 21 830 [26.2%] vs 4262 of 27 545 [15.5%]; P < .001) and those with both T2D and CKD (2905 of 12 236 [23.7%] vs 7078 vs 37 139 [19.1%]; P < .001). Patients prescribed SGLT2i therapy were more likely to be prescribed background triple therapy with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, β-blocker, and mineralocorticoid receptor antagonist (4624 of 9988 [46.3%] vs 10 880 of 39 411 [27.6%]; P < .001), and 4624 of 49 399 total study patients (9.4%) were discharged with prescriptions for quadruple medical therapy including SGLT2i. Among 461 hospitals with 10 or more eligible discharges, 19 hospitals (4.1%) discharged 50% or more of patients with prescriptions for SGLT2i, whereas 344 hospitals (74.6%) discharged less than 25% of patients with prescriptions for SGLT2i (including 29 [6.3%] that discharged zero patients with SGLT2i prescriptions). There was high between-hospital variance in the rate of SGLT2i prescription in unadjusted models (median odds ratio, 2.53; 95% CI, 2.36-2.74) and after adjustment for patient and hospital characteristics (median odds ratio, 2.51; 95% CI, 2.34-2.71).

Conclusions and relevance: In this study, prescription of SGLT2i at hospital discharge among eligible patients with HFrEF was low, including among patients with comorbid CKD and T2D who have multiple indications for therapy, with substantial variation among US hospitals. Further efforts are needed to overcome implementation barriers and improve use of SGLT2i among patients with HFrEF.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Vaduganathan has received personal fees from Amgen, AstraZeneca, Baxter HealthCare, Bayer AG, Boehringer Ingelheim, Cytokinetics, Pharmacosmos, Relypsa, American Regent, Novartis, Roche Diagnostics, Lexicon Pharmaceuticals, Galmed, Occlutech, Impulse Dynamics, Sanofi, Tricog Health, Novo Nordisk, Chiesi, and Merck outside the submitted work. Dr Fonarow has received personal fees from Abbott, AstraZeneca, Amgen, Bayer, Cytokinetics, Eli Lilly, Janssen, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer outside the submitted work. Dr Butler has received personal fees from Boehringer Ingelheim during the conduct of the study as well as personal fees from Abbott, Adrenomed, American Regent, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squib, Cardior, CVRx, Eli Lilly, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Occlutech, Pfizer, Relypsa, Roche, V-Wave Limited, Sequana Medical, and Vifor outside the submitted work. Dr DeVore has received research funding through his institution from the American Heart Association, Biofourmis, Bodyport, Cytokinetics, American Regent, National Heart, Lung, and Blood Institute, Novartis, and Story Health as well as personal fees from Abiomed, AstraZeneca, Cardionomic, InnaMed, LivaNova, Natera, Novartis, Novo Nordisk, Procyrion, Story Health, Vifor, and Zoll during the conduct of the study and nonfinancial support from Abbott outside the submitted work. Dr Joynt Maddox has received grants from the National Institutes of Health; personal fees from Centene Health Policy Advisory Council; and research funding from Humana outside the submitted work. Dr Owens has grants from Bristol Myers Squibb as well as personal fees from Bristol Myers Squibb, Cytokinetics, Renovacor, Tenaya, Lexicon, Edgewise, Biomarin, and Stealth outside the submitted work. Dr Solomon has received grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI and personal fees from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health outside the submitted work. Dr Vardeny has received grants from AstraZeneca, Bayer, and Cardurion as well as personal fees from Cardior outside the submitted work. Dr Yancy’s spouse is employed by Abbott Labs. Dr Greene has received personal fees from AstraZeneca during the conduct of the study; personal fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Corteria Therapeutics, Cytokinentics, Merck, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Urovant Pharmaceuticals, and CSL Vifor; nonfinancial support from AstraZeneca, Novartis, Boehringer Ingelheim, Sanofi, Pfizer, Merck, and Bristol Myers Squibb; and grants from Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Discharge Use of Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) Therapy Overall and Among Demographic and Clinical Subgroups
Rates of discharge prescription of SGLT2i overall and among demographic subgroups (sex, age, race and ethnicity) and clinical subgroups (type 2 diabetes [T2D], chronic kidney disease [CKD], and a combination of T2D and CKD).
Figure 2.
Figure 2.. Hospital-Level Variation in Percentage of Patients Discharged With Prescription for Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i)
Hospital-level variation in discharge prescription of SGLT2i among eligible hospital discharges. Data are from only those hospitals contributing 10 or more eligible discharges (461 of 489 total hospitals [94.2%]). GWTG-HF indicates Get With The Guidelines–Heart Failure.
Figure 3.
Figure 3.. Patient-Level and Hospital-Level Characteristics Independently Associated With Discharge Use of Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) Therapy
Forest plot depicting adjusted odds ratios (ORs) for SGLT2i prescription for patient and hospital characteristics included in the multivariable logistic regression model after backward variable selection. A P value threshold of .20 was used for backward variable selection. Kidney insufficiency was defined as chronic serum creatinine elevation greater than 2.0 mg/dL (to convert to micromoles per liter, multiply by 88.4). BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); EF, ejection fraction; eGFR, estimated glomerular filtration rate; HMO; health maintenance organization; ICD, implantable cardioverter-defibrillator; TIA, transient ischemic attack.
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