- Design
- Prespecified subgroup analysis of HELIOS-B, a randomised placebo-controlled trial
- Population
- 654 people with ATTR cardiomyopathy; 259 (40%) on tafamidis at baseline
- Primary outcome
- All-cause mortality and recurrent cardiovascular events, by baseline tafamidis use
- Effect
- Rate ratio 0.79 (0.51 to 1.21) with tafamidis; 0.67 (0.49 to 0.93) without; interaction P = 0.55
This is a subgroup analysis of HELIOS-B, in which 654 people with transthyretin amyloid cardiomyopathy received vutrisiran 25 mg or placebo every three months for up to 36 months. Tafamidis was allowed, and 259 participants (40%) were taking it at baseline.
For the primary outcome of all-cause death and recurrent cardiovascular events, the rate ratio was 0.79 (95% CI 0.51 to 1.21) in those on tafamidis and 0.67 (0.49 to 0.93) in those not on it. The test for interaction was not significant (P = 0.55). Results for the components were similar, but effect sizes were numerically smaller on tafamidis. Six-minute walk distance was preserved in both groups; the improvement in the KCCQ health-status score looked weaker in those on tafamidis.
The subgroup was defined by baseline use rather than randomised, and the confidence interval in the tafamidis stratum is wide. The analysis cannot tell you whether combination therapy adds benefit. The authors call for prospective studies.
- Do not read this as proof that adding vutrisiran to tafamidis works, or that it does not.
- The tafamidis subgroup had 259 people, so its interval crosses 1.
- Health-status gains on the KCCQ looked smaller on baseline tafamidis.
- Availability and cost of both agents will decide most decisions in India; neither is established here by this paper.
Why it matters
It looks inside a major ATTR-CM trial at a question clinicians already face: what to do for someone already on a stabiliser.
Don't overread it
Baseline tafamidis use was not randomised, so the subgroup comparison is observational in nature.
The statistics, in plain English
A non-significant interaction test means the data do not show that the treatment effect differs between groups; it does not show that the effects are the same. Subgroups are smaller, so their intervals are wider.
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