SGLT2 Inhibitor Therapy in ATTR Cardiomyopathy

Quick Takes

  • In a propensity-matched study of an observational cohort, use of SGLT2 inhibitors in patients with TTR cardiomyopathy was associated with a reduction in all-cause and CV mortality, worsening HF symptoms, and renal function.
  • SGLT2 inhibitors were well tolerated with a discontinuation rate of 4.5% and systolic BP did not change significantly with use.
  • Benefits persisted in sensitivity analyses accounting for disease-modifying treatments such as tafamidis and patisiran.

Study Questions:

What is the effectiveness and tolerability of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with transthyretin amyloidosis (ATTR) and heart failure (HF)?


The authors used a multicenter, longitudinal, observational, propensity-matched cohort across 14 centers in Europe and North America. ATTR was diagnosed based on HF symptoms with a positive Tc99m-PYP scan or endomyocardial biopsy confirming ATTR. Propensity matching was performed on the likelihood of treatment with SGLT2i and endpoints included all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization.


There were 2,356 patients with ATTR between 2014–2022 and 260 (11%) received SGLT2i. After propensity matching, 220 patients treated with SGLT2i were compared with 220 patients who did not. Mean age was 77 years and 90% were males with a mean left ventricular ejection fraction (LVEF) of 46%. Beta-blockers, angiotensin antagonists, and mineralocorticoid-receptor antagonists were prescribed in 59%, 44%, and 46%, respectively and tafamidis/patisiran in 21%. SGLT2i use was prompted by presence of HF and diabetes mellitus. Over a median follow-up of 28 months, only 10 patients (4%) discontinued their SGLT2i, most commonly due to a urinary tract infection. Use of an SGLT2i decreased rates of all-cause mortality (odds ratio, 0.57; 95% confidence interval, 0.37-0.89), CV mortality, worsening HF, and reduction in glomerular filtration rate with no changes in systolic blood pressure (SBP). Need for a loop diuretic also decreased with an SGLT2i. These effects were noted regardless of diabetes status, use of tafamidis/patisiran, and wild-type or hereditary ATTR.


In a propensity-matched analysis of observational data from 440 patients with ATTR cardiomyopathy and HF, use of SGLT2i was associated with a reduction in all-cause and CV mortality and rate of worsening HF and renal function. Discontinuation rate was low at 4% and SBP was not impacted by treatment.


SGLT2i are part of standard of care for HF therapy across all ranges of EF. However, data on their efficacy in cardiac amyloidosis are sparse; therefore, clinical practice relies on extending results from trials of SGLT2i in HF to cardiac amyloidosis. This observational study of ATTR amyloidosis patients suggests that SGLT2i demonstrate significant benefits in almost every endpoint that is important for HF patients including mortality, worsening HF, and renal function.

Noteworthy findings include the fact that use of these medications did not impact SBP, which is often a barrier in use of GDMT in amyloidosis due to co-existent neuropathy in ATTR. Additionally, these medications were very well tolerated with a discontinuation rate of 4.5%. Real-world data often suggest higher rates of adverse events than in clinical trials. Finally, benefits of SGLT2i in ATTR persisted in sensitivity analyses, accounting for use of disease-modifying therapies including tafamidis and patisiran. The authors conducted several analyses including time-varying Cox models accounting for immortal time bias; the study remains an observational study. While a randomized trial would be ideal for answering this question, conducting such a study for a rare disease such as amyloidosis is challenging.

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: Cardiac Amyloidosis, Sodium-Glucose Transporter 2 Inhibitors

< Back to Listings