Sodium-glucose cotransporter-2 inhibitors (SGLT2is) appeared to be safe for patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and could provide benefits such as fewer hospitalizations and improved kidney function, according to a recent study published in Cureus.
Although the outcomes were not statistically significant, the results suggested this class of drugs has a promising role in managing this complex condition and may warrant further research.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
The results could be a step toward addressing unmet needs in the retreatment of ATTR-CM. While the findings are preliminary, they pave the way for larger studies to explore how SGLT2is could improve outcomes in this rare and challenging condition.
“Our single-center study demonstrated the long-term safety of SGLT2i therapy in the treatment of heart failure due to cardiac amyloidosis,” the study authors said.
“Patients treated with SGLT2is did not experience higher-than-expected rates of treatment discontinuation or treatment-limiting adverse effects such as acute kidney injury, orthostatic hypotension, or urinary tract infections.”
Read more about ATTR-CM therapies
They added: “Although our study suggested potentially improved outcomes in the form of preserved functional status, reduced hospitalizations, and improvements in microalbuminuria, these differences were not statistically significant and limited by the sample size and low event rate.”
In the retrospective study, 53 patients with ATTR-CM were treated with empagliflozin (89%) or dapagliflozin (11%) at standard doses. The group, with a mean age of 81 years, included 72% men and predominantly those with wild-type ATTR-CM (74%).
Despite challenges posed by advanced age and comorbidities such as chronic kidney disease (51%) and diabetes (32%), SGLT2i therapy was well-tolerated. Only 6% of participants experienced urinary tract infections, and 3.8% developed acute kidney injury. Notably, no cases of new orthostatic hypotension occurred during treatment.
This study observed trends toward improved outcomes. Hospitalizations decreased from a median of one per year to 0.6 per year, while functional status improved, with more patients moving from New York Heart Association Class III to Class II.
Indicators of kidney function, such as microalbuminuria, also showed improvement, with albumin-to-creatinine ratios declining from 53.8 mg/g to 29.2 mg/g. However, the changes did not reach statistical significance, potentially due to the small sample size.
The research highlighted the compatibility of SGLT2is with other guideline-directed medical therapies. Nearly all participants were prescribed additional medications, such as mineralocorticoid receptor antagonists, without adverse interactions. This combination may enhance the treatment of ATTR-CM, which is characterized by the deposition of misfolded proteins in the heart, impairing its function.
SGLT2is are generally avoided in certain heart conditions out of concerns about worsening symptoms, such as orthostatic hypotension. However, the study suggested they can be safely used in patients with ATTR-CM, aligning with their established benefits in other types of heart failure.