AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Vutrisiran versus Tafamidis in Transthyretin Amyloid Cardiomyopathy: A Propensity-Matched Real-World Analysis of Cardiovascular Outcomes
By Bahar Y, Bahar AR, Awad A et al.
Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative cardiomyopathy associated with worsening heart failure (HF), arrhythmias, and increased mortality. Tafamidis, a transthyretin stabilizer, and vutrisiran, an RNA interference therapy that suppresses transthyretin production, have both demonstrated clinical benefit in ATTR-CM. However, real-world comparative data evaluating cardiovascular outcomes associated with these therapies are limited. We sought to compare clinical outcomes among patients with ATTR-CM treated with vutrisiran versus tafamidis. Methods: We performed a retrospective cohort study using the TriNetX global research network. Adults with ATTR-CM treated with vutrisiran or tafamidis were identified and underwent 1:1 propensity score matching for demographics, comorbidities, and cardiovascular risk factors. The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke. Secondary outcomes included HF exacerbation, new-onset atrial fibrillation (AF), ventricular arrhythmias, conduction disorders, pacemaker implantation, and implantable cardioverter-defibrillator (ICD) implantation. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using chi-square testing. Time-to-event analyses were additionally evaluated using Kaplan-Meier methods and Cox proportional hazards regression. Results: After propensity score matching, 1,147 patients were included in each cohort. Median follow-up was 249 days in the vutrisiran cohort and 260 days in the tafamidis cohort. Compared with tafamidis, vutrisiran was associated with a significantly lower risk of the composite endpoint (RR 0.61, 95% CI 0.49-0.75; p<0.001), all-cause mortality (RR 0.60, 95% CI 0.43-0.83; p=0.002), myocardial infarction (RR 0.68, 95% CI 0.47-0.97; p=0.030), stroke (RR 0.37, 95% CI 0.20-0.66; p<0.001), heart failure exacerbation (RR 0.54, 95% CI 0.37-0.80; p=0.002), and pacemaker implantation (RR 0.71, 95% CI 0.57-0.89; p=0.003). Risks of new-onset atrial fibrillation (RR 0.82, 95% CI 0.57-1.20; p=0.315), ICD implantation (RR 0.78, 95% CI 0.58-1.04; p=0.093), ventricular arrhythmias (RR 1.03, 95% CI 0.82-1.31; p=0.789), and conduction disorders (RR 1.02, 95% CI 0.87-1.20; p=0.796) were similar between groups. Conclusions: In this analysis of a real-world database of patients with ATTR-CM treated with vutrisiran or tafamidis, vutrisiran was associated with lower risks of mortality, heart failure exacerbation, and adverse cardiovascular events compared with tafamidis. These findings may have important implications for therapeutic selection as disease-modifying treatment options for ATTR-CM continue to expand.