Long-term efficacy of vutrisiran in patients with variant transthyretin amyloid cardiomyopathy

Background Real-world evidence regarding the efficacy of vutrisiran in patients with variant transthyretin amyloid cardiomyopathy (ATTRv-CM) remains limited. This study aimed to retrospectively evaluate the real-world long-term effects of vutrisiran on clinical parameters and cardiovascular outcomes in patients with ATTRv-CM. Methods Eighteen patients with ATTRv-CM from our cohort were retrospectively analyzed. Of these, 10 patients who initiated vutrisiran therapy were assigned to the vutrisiran-naïve group, whereas 8 patients who switched from patisiran to vutrisiran were assigned to the vutrisiran-switch group. Longitudinal changes in troponin T, NT-proBNP, transthyretin (TTR) levels, and echocardiographic parameters were assessed from baseline to 1 year after initiation of vutrisiran therapy. Clinical outcomes following vutrisiran initiation, including all-cause mortality and hospitalization for heart failure, were also evaluated. Results Following vutrisiran therapy, troponin T levels significantly decreased at 1 year compared with baseline in the vutrisiran-naïve group, whereas NT-proBNP and TTR levels significantly decreased in both groups (vutrisiran-naïve group: troponin T, 0.040 to 0.038 ng/mL, p=0.049; NT-proBNP, 1289 to 699 pg/mL, p=0.020; TTR, 14.1 to 0.65 mg/dL, p=0.002; vutrisiran-switch group: troponin T, 0.028 to 0.036 ng/mL, p=0.36; NT-proBNP, 1516 to 1072 pg/mL, p=0.039; TTR, 2.8 to 0.45 mg/dL, p=0.008; Figure 1). Regarding echocardiographic parameters, no significant changes were observed in left ventricular ejection fraction, interventricular septal thickness, or left ventricular mass in either group; however, E/e′ significantly decreased in both groups (vutrisiran-naïve group: 15.7 to 12.1, p=0.031; vutrisiran-switch group: 16.7 to 14.5, p=0.023; Figure 2). During follow-up, two patients experienced hospitalization for heart failure, and one patient died of a non-cardiovascular cause. Conclusions Vutrisiran demonstrated favorable real-world clinical efficacy in patients with ATTRv-CM in our cohort.