Combination therapy with SGLT2-inhibitors and tafamidis in transthyretin cardiomyopathy.

BACKGROUND

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease associated with high morbidity and mortality. Tafamidis is the only US Food and Drug Administration-approved disease-modifying therapy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) have shown promise in heart failure and may offer additive benefit when combined with tafamidis, although this remains unclear.

METHODS

Using the TriNetX global research network, we identified adults with ATTR-CM treated with tafamidis between 2019 and 2022. Patients were stratified by concomitant use of SGLT2-Is (empagliflozin, dapagliflozin, or canagliflozin). Primary outcome was all-cause mortality; secondary outcomes included all-cause hospitalizations, acute myocardial infarction (AMI), stroke, heart failure hospitalizations, arrhythmias, and end-stage renal disease at 1- and 3-year follow-up.

RESULTS

After matching, 409 patients remained in each cohort. Combination therapy with SGLT2-Is and tafamidis was associated with significantly lower all-cause hospitalizations (1-year: OR 0.67, p = 0.005; 3-year: OR 0.67, p = 0.006) and AMI (1-year: OR 0.44, p = 0.001; 3-year: OR 0.56, p = 0.004). No significant mortality reduction was observed at either time point. No significant differences were observed for any of the other secondary outcomes.

CONCLUSIONS

In patients with ATTR-CM treated with tafamidis, adjunctive SGLT2-I use was associated with lower rates of hospitalization and AMI, without a significant mortality benefit. These findings support further prospective evaluation of combination therapy.