Association Of Sodium-Glucose Co-transporter 2 Inhibitors Use On Clinical Outcomes In Patients With Wild-type Transthyretin Amyloid Cardiomyopathy: A Retrospective Cohort Study

Background

Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is a progressive restrictive cardiomyopathy characterized by the deposition of misfolded transthyretin in myocardium resulting in high mortality. The burden of this disease and its clinical trajectory are further exacerbated by the presence of concomitant type II diabetes mellitus (T2DM). Sodium-glucose co-transporter 2 inhibitors (SGLT2i), initially demonstrating improved heart failure (HF) hospitalizations in those with T2DM, are now recommended for use across the spectrum of left ventricular ejection fraction, regardless of T2DM status. However, there are limited data regarding the use of SGLT2i in wATTR-CM patients.

Methods

This study utilized real-world EHR-based dataset (TriNetX, Inc.) that collects health records from academic medical center network across the United States. This platform was used to identify individuals diagnosed with wATTR-CM and having T2DM, using standardized ICD-10 and RxNorm codes to define population characteristics and identifying study outcomes. The study population was stratified based on SGLT2i use at the time of diagnosis of wATTR-CM. The primary study outcome was all-cause mortality at 3 years. The secondary study outcomes included incident atrial fibrillation, end-stage renal disease (ESRD), ventricular tachycardia/ventricular fibrillation (VT/VF), and stroke. Propensity-score matching (1:1) was used to balance the study population groups based on demographics, Elixhauser comorbidities, and Tafamidis use.

Results

A total population of 1,276 wTTR-CM patients with T2DM were identified, with 421 (33%) patients receiving SGLT2i. After matching, 381 patients were identified in each study group (those using SGLT2i and not using SGLT2i). In the setting of similar background use of Tafamidis (37.6% vs. 40.3%), the risk of all-cause mortality at 3-years was significantly lower among wATTR-CM patients with T2DM on SGLT2i compared with those not on SGLT2i (14.4% vs. 26.0%, HR: 0.53 [95% CI: 0.38-0.74]) (Figure). Treatment with SGLT2i among wATTR-CM patients with T2DM was associated with a similar risk for developing atrial fibrillation (28.8% vs. 24.6%, HR: 1.05, 95% CI: 0.66-1.66), ESRD (2.8% vs. 4.3%; HR: 0.50, 95% CI: 0.21-1.19), VT/VF (15.3% vs. 13.2%; HR: 1.14, 95% CI: 0.74-1.76), and stroke (7.3% vs. 4.3%; HR: 1.63, 95% CI: 0.82-3.25).

Conclusions

This observational study indicates that SGLT2i use among wATTR-CM patients having T2DM is associated with a lower risk of all-cause mortality. These findings support prospective randomized clinical trials evaluating the cardioprotective efficacy of SGLT2i in wATTR-CM.