Effect of vutrisiran in patients with and without atrial fibrillation or flutter: analysis from HELIOS-B
X Wang, M Fontana, B Claggett, K S Jering, R Witteles, K Tsujita, C Morbach, F H Sheikh, P Y Jay, S D SolomonAbstract
Background
Among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), vutrisiran reduced the risk of all-cause death and cardiovascular events. Atrial fibrillation, a sign of advanced heart disease, is common among patients with ATTR-CM. Whether the efficacy of vutrisiran is consistent in patients with and without atrial fibrillation is unknown.
Purpose
To evaluate the efficacy of vutrisiran in patients with and without atrial fibrillation or flutter (AF/AFL) in the HELIOS-B trial.
Methods
We performed a secondary analysis of the double-blind, randomized-controlled HELIOS-B trial of vutrisiran versus placebo in patients with ATTR-CM. Baseline clinical and echocardiographic characteristics were compared in patients with no history of AF/AFL and with evidence of AF/AFL (either by history or on enrollment electrocardiogram [ECG]). Primary end point (all-cause death and recurrent cardiovascular events) was analyzed using LWYY model. Secondary end points were analyzed using Cox proportional hazards models. All models were adjusted for baseline N-terminal pro-B type natriuretic peptide (NT-proBNP) level and stratified by baseline tafamidis use.
Results
Among 654 participants, 422 (65%) had history of AF/AFL or AF/AFL on enrollment ECG. Patients with history of AF/AFL or AF/AFL on ECG were older, more likely to be male, have New York Heart Association (NYHA) Class III symptoms, worse amyloidosis disease stage, wild-type ATTR, and had lower Kansas City Cardiomyopathy Questionnaire (KCCQ) scores (Table 1). Compared to patients with no AF/AFL, those with evidence of AF/AFL had higher left atrial volume index and lower left ventricular (LV) ejection fraction, LV stroke volume index, LV absolute global longitudinal strain, and tricuspid annular early systolic velocity. Vutrisiran reduced the rate of primary end point in those without AF/AFL (rate ratio [RR] 0.76 [0.49-1.17]) and in those with evidence of AF/AFL (RR 0.67 [0.49 – 0.93], P-interaction = 0.62). The treatment effect of vutrisiran was also similar for secondary end points regardless of AF/AFL status (P-interaction > 0.20 for all, Figure 1).
Conclusions
In participants in HELIOS-B trial, those with evidence of AF/AFL were older, with more symptom burden, and worse health status. Patients with AF/AFL had worse LV and RV systolic function. Compared to placebo, vutrisiran lowered the risk of all-cause death and recurrent cardiovascular events in patients with and without evidence of AF/AFL.Table 1.Baseline CharacteristicsFor image description, please refer to the figure legend and surrounding text.Figure 1.Treatment EffectFor image description, please refer to the figure legend and surrounding text.