This pre-specified subgroup analysis of the HELIOS-B RCT examined whether the treatment effect of vutrisiran (25 mg SC every 3 months for up to 36 months) on all-cause mortality and recurrent cardiovascular events differed based on whether patients with ATTR-CM were already taking tafamidis at baseline (n=259, 40%) versus not (n=395, 60%).
Vutrisiran's benefit was directionally consistent regardless of baseline tafamidis use (rate ratio 0.79 [95% CI: 0.51–1.21] with tafamidis vs 0.67 [95% CI: 0.49–0.93] without; P-interaction = 0.55), but effect sizes were numerically smaller in patients already on tafamidis, and KCCQ-OSS improvement appeared attenuated in that group.
This is a subgroup analysis with the tafamidis stratum not powered to detect a statistically significant interaction; the confidence intervals for the combination therapy group are wide and cross 1.0, preventing definitive conclusions about additive benefit.
Vutrisiran shows consistent directional benefit whether or not patients are on tafamidis, but the smaller effect size in those already stabilized on tafamidis means clinicians should not assume full additive benefit — prospective combination therapy trials are needed before routinely combining these agents.
