SPC365

From Trials to Practice: Early Use of Vutrisiran in ATTR-CM

Session: Sessão de Posters 12 - Estratégias terapêuticas e desfechos em vida real na ATTR-CM
Speaker: Catarina Sena Silva

Congress: CPC 2026
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.4 Myocardial Disease – Treatment
Session Type: Posters Eletrónicos
FP Number: ---
Authors: Catarina Sena Silva; Daniel Inácio Cazeiro; Marta Vilela; Diogo Ferreira; João Cravo; João Fernandes Pedro; Inês Araújo; Catarina Campos; Isabel Conceição; Fausto J. Pinto; Dulce Brito; João R. Agostinho

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Introduction:</strong></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive and life-threatening disorder characterized by the deposition of misfolded transthyretin (TTR) in cardiac tissue. Vutrisiran, a subcutaneously administered RNA interference (RNAi) therapeutic, has emerged as a promising treatment by silencing the TTR gene and thereby inhibiting hepatic protein production. Clinical studies have demonstrated reductions in circulating TTR levels of over 80% after 18 months of treatment. Additionally, vutrisiran has been shown to reduce all-cause mortality and cardiovascular events, while preserving functional capacity and quality of life.</span></span></span></p>

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<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Aim:</strong></span></span></span><br />
<span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">To evaluate the real-world safety and effectiveness of vutrisiran in patients with hereditary transthyretin-mediated cardiac amyloidosis (hATTR-CM).</span></span></span></p>

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<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Methods:</strong></span></span></span><br />
<span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">We conducted a prospective, single-center study including patients with hATTR-CM carrying the Val30Met variant who initiated vutrisiran 25 mg administered subcutaneously every 3 months. Clinical, echocardiographic, and laboratory parameters were assessed at baseline (prior to treatment initiation) and after 6 months of therapy.&nbsp;</span></span></span></p>

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<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Results:</strong></span></span></span><br />
<span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Five patients were enrolled (mean age 68 &plusmn; 5 years; 3 [60%] male). Three patients (60%) had previously received tafamidis and were switched to vutrisiran due to clinical progression. After 6 months of treatment, there was a trend toward clinical and functional improvement: no patients remained in NYHA class III&ndash;IV (vs. 2 [40%] at baseline). Diuretic dose decreased (20 mg [IQR 10&ndash;30] vs. 40 mg [IQR 10&ndash;60] at baseline; p = 0.06), and 6-minute walk distance improved significantly (367 &plusmn; 41 m vs. 306 &plusmn; 40 m; p = 0.02).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">Regarding laboratory findings, NT-proBNP levels demonstrated a trend toward reduction at follow-up (358 pg/mL [IQR 246&ndash;892] vs. 456 pg/mL [IQR 353&ndash;2030]; p = 0.06). Serum TTR levels became undetectable in all patients (baseline 27 mg/dL [IQR 6&ndash;33]), with a median time to suppression of 8 weeks (IQR 5&ndash;22). No significant changes were observed in echocardiographic parameters.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">During follow-up, no adverse events, heart failure decompensations, or hospitalizations were recorded. No statistically significant differences were observed between tafamidis-experienced and treatment-na&iuml;ve patients.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Conclusion:</strong></span></span></span><br />
<span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000">In this real-world cohort, vutrisiran was well tolerated and associated with improvements in clinical status and functional capacity. These findings suggest that vutrisiran may represent an effective therapeutic option both for tafamidis non-responders and for treatment-na&iuml;ve hATTR-CM patients.</span></span></span></p>