Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Amyloidosis With or Without Heart Failure - 17/03/25

Doi : 10.1016/j.amjmed.2025.02.010

Silvio N. Augusto Jr., BSc ^a,^b, Rochell Issa, MD ^b,^c, Simon Vanhentenrijk, MD, PharmD ^d, David Kaelber, MD, PhD, MPH ^b, W.H. Wilson Tang, MD ^a,^d,^e,^⁎
^a Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
^b Center for Clinical Informatics Research and Education, The MetroHealth System and the Departments of Internal Medicine, Pediatrics, and Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio
^c Education Institute, Cleveland Clinic, Cleveland, Ohio
^d Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
^e Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio

^⁎Requests for reprints should be addressed to W. H. Wilson Tang, MD, Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, 9500 Euclid Avene, Desk J3-4, Cleveland, OH 44195.Department of Cardiovascular MedicineHeart Vascular and Thoracic InstituteCleveland Clinic9500 Euclid Avene, Desk J3-4ClevelandOH44195

En prensa. Pruebas corregidas por el autor. Disponible en línea desde el Monday 17 March 2025

Abstract

Background

Emerging evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefits may extend to patients with amyloid cardiomyopathy, including transthyretin and amyloid light-chain amyloidosis subtypes. This study explores the broader implications of SGLT2i therapy across the spectrum of amyloidosis.

Methods

This retrospective cohort study used de-identified electronic health records from the TriNetX platform, encompassing data from 101 healthcare organizations between 2009 and 2024. Two cohorts of amyloidosis patients with heart failure were compared based on SGLT2i use. One cohort without a diagnosis of heart failure was also tested. Propensity score matching was applied to balance baseline characteristics. The primary outcome was all-cause mortality, and secondary outcomes included acute heart failure, acute myocardial infarction, stroke, and chronic kidney disease.

Results

The matched cohorts included 5612 patients, with a mean age of 74 years and 64% male. SGLT2i-treated patients exhibited a higher 5-year survival probability (62.6%) compared to non-SGLT2i patients (39.1%) (HR: 0.54, 95% CI: 0.50-0.59; P < .001). In amyloidosis patients without heart failure (n = 1490), SGLT2i therapy was associated with a significant reduction in all-cause mortality (HR: 0.57, 95% CI: 0.43-0.74; P < .001). Sub-cohorts of transthyretin and amyloid light-chain amyloidosis in heart failure patients demonstrated consistent benefits with reduced mortality and favorable trends for acute myocardial infarction and stroke.

Conclusions

SGLT2i therapy is associated with significant survival benefits in amyloidosis patients with HF and may offer broader advantages across the amyloidosis spectrum, including amyloid patients without heart failure.

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Keywords : Amyloid light-chain amyloidosis, Amyloidosis, Heart failure, SGLT2 inhibitors, Transthyretin amyloidosis

Esquema

	Funding: This project was supported in part by the Clinical and Translational Science Collaborative of Northern Ohio which is funded by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health, UM1TR004528. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
	Conflict of Interest: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wai Hong Wilson Tang, MD reports financial support was provided by the National Institutes of Health. Wai Hong Wilson Tang, MD reports a relationship with Cardiol Therapeutics Inc. that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Genomics plc that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Zehna Therapeutics that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Boston Scientific that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with WhiteSwell, Inc. that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with CardiaTec Biosciences that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Bristol-Myers Squibb, Inc. that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Alleviant Medical, Inc. that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Alexion Pharmaceuticals, Inc. that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Salubris Biotherapeutics, Inc. that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with BioCardia, Inc. that includes: consulting or advisory. Wai Hong Wilson Tang, MD reports a relationship with Springer Nature that includes: funding grants. Wai Hong Wilson Tang, MD reports a relationship with Belvoir Media Group that includes: funding grants. Wai Hong Wilson Tang, MD reports a relationship with the American Board of Internal Medicine that includes: consulting or advisory and travel reimbursement.
	Authorship: All authors had access to the data. Silvio N Augusto conducted the analysis, created the figures, wrote the first draft, and reviewed the manuscript. W. H. Wilson Tang idealized the research question and reviewed the manuscript. Rochell Issa, Simon Vanhentenrijk, and David Kaelber reviewed the manuscript. SNA: Writing – original draft, Formal analysis, Data curation, Conceptualization; RI: Writing – review & editing; SV: Writing – review & editing; DK: Writing – review & editing, Resources; WHWT: Writing – review & editing, Supervision, Conceptualization