All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.

FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).

All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.

Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS. FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).

The 6-MWT is an assessment of functional exercise capacity. Participants are instructed to walk back and forth along a flat, straight path, typically 30 meters in length, for a duration of 6 minutes. The total distance covered in meters is recorded at the end of 6 minutes. A longer distance reflects a better outcome. Analysis was based on the mixed-effect model of repeated measures (MMRM). Missing change values due to amyloidosis disease progression and death were imputed using sampling with replacement from the worst 10% of observed values, as specified in the statistical analysis plan (SAP).

FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo). Overall number analyzed is the number of participants with data available for analysis.

The 6-MWT is an assessment of functional exercise capacity. Participants are instructed to walk back and forth along a flat, straight path, typically 30 meters in length, for a duration of 6 minutes. The total distance covered in meters is recorded at the end of 6 minutes. A longer distance reflects a better outcome. Analysis was based on the MMRM. Missing change values due to amyloidosis disease progression and death were imputed using sampling with replacement from the worst 10% of observed values, as specified in the SAP.

Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS. FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).

The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms [frequency and burden], physical function, quality of life (QoL), social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores were generated for each domain and transformed to a range of 0-100, in which higher scores reflect better health status. KCCQ- overall summary score was average of domains- physical function, total symptoms (average of symptom frequency and burden), QoL, and social limitation, and transformed to a single score which ranged from 0 (worst) - 100 (the best possible status), where the higher score reflected better health status. Analysis was based on the MMRM.

FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo). Overall number analyzed is the number of participants with data available for analysis.

The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms [frequency and burden], physical function, QoL, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and OS). Scores were generated for each domain and transformed to a range of 0-100, in which higher scores reflect better health status. KCCQ- overall summary score was average of domains- physical function, total symptoms (average of symptom frequency and burden), QoL, and social limitation, and transformed to a single score which ranged from 0 (worst) - 100 (the best possible status), where the higher score reflected better health status. Analysis was based on the MMRM.

Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS. Overall number analyzed is the number of participants with data available for analysis.

All-cause mortality also included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits.

NYHA class is a clinical assessment of symptoms resulting from heart failure. In NYHA functional classification system places participants in 1 of 4 categories based on limitations of physical activity. Class I denotes no symptoms and no limitation of physical activity; II, slight limitation, resulting in symptoms with ordinary physical activity; III, marked limitation, resulting in symptoms with less than ordinary physical activity; and IV, symptoms at rest. Here, the participants with a change in NYHA class have been reported in two categories:

1) participants who had no change or had improvement in the NYHA class (lower class) from baseline and 2) participants who had a worsened NYHA class from baseline (higher class).

Values have been rounded off to a single decimal.

FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).

NYHA class is a clinical assessment of symptoms resulting from heart failure. In NYHA functional classification system places participants in 1 of 4 categories based on limitations of physical activity. Class I denotes no symptoms and no limitation of physical activity; II, slight limitation, resulting in symptoms with ordinary physical activity; III, marked limitation, resulting in symptoms with less than ordinary physical activity; and IV, symptoms at rest. Here, the participants with a change in NYHA class have been reported in two categories:

1) participants who had no change or had improvement in the NYHA class (lower class) from baseline and 2) participants who had a worsened NYHA class from baseline (higher class).

Values have been rounded off to a single decimal.

Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS.