Abstract Body (Do not enter title and authors here): Background:
Tafamidis is the standard therapy for transthyretin cardiac amyloidosis, but the role of adjunctive medications such as SGLT2 inhibitors, mineralocorticoid receptor antagonists, GLP-1 receptor agonists, and sacubitril/valsartan on patient outcomes remains uncertain.
Objective:
To assess associations between these therapies and clinical outcomes in patients with cardiac amyloidosis receiving tafamidis.
Methods:
Using the TriNetX Research Network, we conducted a multicenter retrospective cohort study of adults initiating tafamidis from January 2019 to April 2025. Exposure to each drug class within 90 days of tafamidis initiation defined treatment groups. Propensity score matching was used. The primary outcome was all-cause mortality at one and five years. Secondary outcomes included heart failure hospitalization or death, major adverse cardiovascular events (MACE), emergency visits, atrial fibrillation, and acute kidney injury.
Results:
Among 5,683 patients, SGLT2 inhibitor use was associated with lower mortality at one year (hazard ratio 0.563; 95% confidence interval 0.416–0.762) and five years (hazard ratio 0.615; 95% confidence interval 0.483–0.782), and with lower odds of heart failure hospitalization or death (odds ratio 0.547; 95% confidence interval 0.454–0.659) and MACE (odds ratio 0.704; 95% confidence interval 0.591–0.839) at five years. Sacubitril/valsartan use was associated with fewer emergency visits (odds ratio 0.744; 95% confidence interval 0.575–0.964) and reduced MACE (odds ratio 0.751; 95% confidence interval 0.575–0.981) at five years. Mineralocorticoid receptor antagonist use was linked to higher odds of atrial fibrillation, acute kidney injury, emergency visits, and MACE at both one and five years. GLP-1 receptor agonist use was associated with fewer emergency visits at one year (odds ratio 0.554; 95% confidence interval 0.318–0.965).
Conclusions:
In patients with cardiac amyloidosis receiving tafamidis, adjunctive use of SGLT2 inhibitors and sacubitril/valsartan was associated with favorable clinical outcomes. Conversely, mineralocorticoid receptor antagonists were linked to increased risks of arrhythmia, renal events, and healthcare utilization.