Ibrahim, R

Abstract Introduction/Background Transthyretin amyloidosis (ATTR) is a debilitating disease that leads to progressive cardiac dysfunction. Tafamidis is the gold standard therapy for ATTR cardiomyopathy. In recent observational studies, sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) have demonstrated cardiovascular benefits in ATTR cardiomyopathy, but their role in ATTR cardiomyopathy as combination therapy with tafamidis remains unclear. Purpose To investigate the impact of combination therapy with tafamidis and SGLT2-Is versus just tafamidis in patients with known ATTR cardiomyopathy. Methods This retrospective cohort study utilized data from the TriNetX multinational database. Patients diagnosed with ATTR cardiomyopathy who received tafamidis were identified and stratified into two cohorts based on SGLT2-I use. Outcomes were assessed over three years, including all-cause mortality, all-cause hospitalizations, acute myocardial infarction (AMI), acute heart failure (HF) hospitalizations, ischemic stroke, atrial fibrillation/flutter, end-stage renal disease (ESRD) or requirement for renal replacement therapy, and ventricular tachycardia. Propensity score matching was used to balance both cohorts based on clinical comorbidities, medication use, and laboratory data. Adjusted odds ratios (OR) were calculated by logistic regression models. Results After propensity score matching, 409 patients were included in each cohort with a follow-up duration of 722 days (SD 320.87) for the SGLT2-I cohort and and 755.90 days (SD 363.26) for the non-SGLT2-I cohort. SGLT2-Is were associated with significantly lower rates of all-cause hospitalizations (41.1% vs. 50.9%; OR 0.67 [p = 0.005]) and AMI (6.6% vs. 13.9%, OR 0.44 [p = 0.001]), which persisted by three years (all-cause hospitalizations: 52.1% vs. 61.4%, OR 0.67 [p = 0.006] and myocardial infarction: 11.2% vs. 18.3%, OR 0.56 [p = 0.004]). No significant differences among the two cohorts were observed for all-cause mortality, acute HF hospitalizations, ischemic stroke, atrial fibrillation/flutter, ventricular tachycardia, or ESRD/need for renal replacement therapy. Conclusions SGLT2-Is, in combination with tafamidis, are associated with decreased all-cause hospitalizations and AMI in ATTR cardiomyopathy. While a mortality benefit was not demonstrated, these results depict the magnitude of clinical benefit derived from combination therapy with tafamidis and SGLT2-Is as opposed to prior observational studies which investigated SGLT2-I single therapy

Abstract Background/Introduction Patients with transthyretin cardiac amyloidosis (ATTR-CA) and atrial fibrillation (AF) have increased risk for left atrial thrombi, necessitating anticoagulation therapy if bleeding risk is not prohibitive. Limited data is available comparing the use of direct oral anticoagulants (DOACs) to warfarin in this population. Purpose To evaluate and compare clinical efficacy and safety outcomes of DOACs versus warfarin in patients with ATTR-CA and AF. Methods We conducted a retrospective cohort study using the TriNetX Network, which includes data from over 140 million patients, between 2014 and 2022. Adults (aged ≥18 years) with ATTR-CA and AF were identified. These patients were further categorized into two groups: one cohort which utilized DOACs for oral anticoagulation and the other cohort on warfarin. 1:1 propensity score matching (PSM) was utilized to balance baseline characteristics between the two cohorts. The primary outcome was rate of stroke, with secondary outcomes including all-cause death, all-cause hospitalizations, and acute heart failure exacerbations. Safety outcomes included intracranial hemorrhage, gastrointestinal hemorrhage, and hematuria. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Results Among 8,214 adults with ATTR-CA and AF, 5,774 patients were on a DOAC while 2,440 patients were on warfarin. After PSM, 2,425 patients were included in each group. The use of DOACs for AF in patients with ATTR-CA was associated with a significantly lower risk of ischemic stroke compared to warfarin (5.7% versus 7.3%, aOR 0.771 [95% CI, 0.612-0.971]) by the end of the one year follow up. There were no differences in all-cause mortality (19.8% versus 21%, aOR 0.927 [95% CI, 0.806-1.066]), all-cause hospitalizations (19.2% versus 21.6%, aOR 0.863 [95% CI, 0.624-1.195]) or heart failure exacerbations (43.6% versus 46%, aOR 0.906 [95% CI, 0.809-1.015]). Safety outcomes favored DOACs over warfarin, with a lower risk of intracranial hemorrhage (4.5% versus 7.8%, aOR 0.565 [95% CI, 0.444-0.720]), and comparable rates of GI hemorrhage and hematuria. Conclusions DOACs may be safely used in ATTR-CA patients with AF, offering a lower risk of stroke compared to warfarin and a more favorable safety profile. These findings emphasize the potential advantages of DOACs in this population and underline the need for prospective studies to validate these results.