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. 2024 Oct 8;13(19):5966.
doi: 10.3390/jcm13195966.

Impact of SGLT2-Inhibitor Therapy on Survival in Patients with Transthyretin Amyloid Cardiomyopathy: Analysis of a Prospective Registry Study

Nora Schwegel  1 , Christina Toferer  1 , David K Zach  1 , Viktoria Santner  1 , Viktoria Höller  1 , Jakob Lugitsch  1 , Markus Wallner  1 , Johannes Gollmer  1 , Faisal Aziz  2 , Dirk von Lewinski  1 , Ewald Kolesnik  1 , Klemens Ablasser  1 , Andreas Zirlik  1 , Harald Sourij  2 , Nicolas Verheyen  1
Affiliations

Impact of SGLT2-Inhibitor Therapy on Survival in Patients with Transthyretin Amyloid Cardiomyopathy: Analysis of a Prospective Registry Study

Nora Schwegel et al. J Clin Med. .

Abstract

Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) represent a high-risk heart failure population with continued unmet therapeutic needs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction, and first evidence regarding their safety and effectiveness in patients with ATTR-CM is arising. This study investigates the association between SGLT2i therapy and clinical outcomes in these patients. Methods: This is an analysis of a prospective registry conducted at a referral centre for hypertrophic cardiomyopathies including 116 patients with confirmed ATTR-CM. Fifty-one patients (44%) were treated with SGLT2i while 65 patients (56%) remained SGLT2i-naïve. Results: During a median follow-up of 2.6 (1.7-3.7) years, 38 patients (33%) died, of whom 11 patients (9%) received SGLT2i treatment and 27 patients (23%) were treatment-naïve. SGLT2i therapy was significantly associated with lower mortality (HR 0.457, 95%CI 0.227-0.922, p = 0.029). This association persisted after adjusting for age and sex (HR 0.479, 95%CI 0.235-0.977, p = 0.043) and after additional adjustment for eGFR, NT-proBNP, LVEF, and concomitant therapy with tafamidis (HR 0.328, 95%CI 0.141-0.760, p = 0.009). However, when potential immortal time bias was considered, this association lost statistical significance (HR 1.075, 95%CI 0.524-2.206, p = 0.843). No significant associations between SGLT2i therapy and worsening heart-failure hospitalization or cardiovascular mortality were observed. Conclusions: In crude analysis, SGLT2i therapy associates with better survival in patients with ATTR-CM. However, after adjustment for immortal time, this association becomes statistically insignificant. Hence, to draw final conclusions on the effectiveness of SGLT2i therapy in these patients, a randomized controlled trial is warranted.

Keywords: Sodium–glucose co-transporter 2 inhibitors; heart failure therapy; survival; transthyretin amyloid cardiomyopathy.

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Conflict of interest statement

H.S. is on the advisory board and speakers bureau of Boehringer Ingelheim, NovoNordisk, Amgen, AstraZeneca, Bayer, Eli Lilly, Cancom, MSD, and Daiichi Sankyo. N.V. has received an unrestricted grant from Boehringer Ingelheim. All other authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart of patient disposition. Patient disposition and Sodium–glucose co-transporter 2 inhibitor (SGLT2i) treatment status of included patients.
Figure 2
Figure 2
Associations between SGLT2i therapy and all-cause mortality. Kaplan Meier plot illustrating event probability for all-cause mortality with (blue) and without (red) sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy.
See this image and copyright information in PMC

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