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. 2024 Dec;30(12):1641-1646.
doi: 10.1016/j.cardfail.2024.06.009. Epub 2024 Jul 10.

Safety and Efficacy of SGLT2 Inhibitors for Amyloid Light-Chain Cardiomyopathy

Frederick M Lang  1 , Sergio Teruya  1 , Margaret Cuomo  1 , Alfonsina Mirabal Santos  1 , Jai Radhakrishnan  2 , Suzanne Lentzsch  3 , Rajshekhar Chakraborty  3 , Divaya Bhutani  3 , Mathew S Maurer  4
Affiliations

Safety and Efficacy of SGLT2 Inhibitors for Amyloid Light-Chain Cardiomyopathy

Frederick M Lang et al. J Card Fail. 2024 Dec.

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated benefit in patients with heart failure, but minimal data exist concerning the use of these medications in amyloid light-chain cardiomyopathy (AL-CM). We performed a retrospective study to assess the safety and efficacy of SGLT2is in AL-CM.

Methods: We queried our institutional registry and identified 27 patients with AL-CM who received SGLT2is. The safety analysis included all 27 patients and assessed SGLT2i-associated adverse events, hospitalizations and deaths. To decrease confounding, the efficacy analysis included only a subset of patients with stable disease (on stable anti-plasma cell therapy for ≥ 2 months prior to baseline and had achieved at least a hematologic Very Good Partial Response) and compared disease-marker changes in these patients (n = 17) with those of a contemporaneous untreated control cohort from our registry (n = 21).

Results: The mean age of the overall population was 68.6 (standard deviation 9.4) years. Of the patients, 7 (14.6%) had diabetes, and 19 (39.6%) had chronic kidney disease. In the safety analysis, the median follow-up time was 10.9 (interquartile range 7.2) months. Two (7.4%) patients discontinued SGLT2is due to hypovolemia and genital irritation, and 6 (22.2%) additional patients temporarily held SGLT2is due to an adverse event that is commonly related to volume depletion. There were 13 hospitalizations, all considered unrelated to SGLT2i use, and no deaths occurred. In the efficacy analysis, SGLT2i-treated patients had more severe disease at baseline than controls, demonstrating significantly higher median troponin-T and loop diuretic dosage (P < 0.05). Compared with controls, SGLT2i treatment was associated with significantly greater reductions in loop diuretic dosage (P < 0.001) and NTproBNP levels (P = 0.033) across 3-, 6- and 12-month follow-up timepoints. SGLT2i treatment was also associated with a significantly greater reduction in mean arterial pressure at 12 months (P = 0.031) but not at other timepoints. No significant differences were observed in changes in weight, eGFR, troponin-T, proteinuria, or albumin levels.

Conclusions: In this small-scale retrospective study, we demonstrate that SGLT2is are well tolerated by most patients with AL-CM, but volume depletion symptoms may limit continuous use. SGLT2is may aid management of congestion in AL-CM, as evidenced by reduced diuretic dosage and NTproBNP levels without adverse renal effects. Larger long-term studies are needed to build on our findings.

Keywords: SGLT2 inhibitor; amyloid light-chain; cardiac amyloidosis; chronic kidney disease; guideline-directed medical therapy; heart failure.

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Conflict of interest statement

Disclosures FML holds equity options in Roivant Sciences and has received consulting fees from Roivant Sciences and Kinevant Sciences and declare no conflicts of interest relevant to the contents of this study. MSM reports grant support from NIH R01HL139671 and R01AG081582-01; grants and personal fees from Alnylam, Pfizer, Eidos, Prothena, and Ionis, and personal fees from AstraZeneca, Akcea, Intellia, and Novo-Nordisk. All other authors declare no conflicts of interest related to this work.

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