- Design
- Secondary analysis of a randomised, placebo-controlled trial (HELIOS-B)
- Population
- 654 patients with transthyretin amyloid cardiomyopathy
- Primary outcome
- All-cause death and recurrent cardiovascular events, by concomitant therapy
- Effect
- No effect modification; P-interaction 0.59–0.95 across drug classes
A secondary analysis of HELIOS-B, the trial of vutrisiran in 654 patients with transthyretin amyloid cardiomyopathy, asked whether other treatments changed its effect on the composite of death and recurrent cardiovascular events.
At baseline 40% were on tafamidis and 77% on at least one heart failure drug. Mineralocorticoid receptor antagonists and SGLT2 inhibitors were the drugs most often started during follow-up, more often in the placebo arm. No drug class modified vutrisiran's effect, with interaction P values from 0.59 to 0.95.
For clinicians, this suggests vutrisiran's effect is not confined to patients off tafamidis, and that heart failure drugs can be used alongside it. It does not show that combining vutrisiran with tafamidis is better than either alone.
- Continue guideline heart failure drugs, including SGLT2 inhibitors and MRAs, in patients on vutrisiran
- Do not withhold vutrisiran because a patient is already on tafamidis, on this evidence
- Note that the trial did not test whether dual transthyretin therapy beats one agent
Why it matters
It answers whether the trial result applies to patients already on contemporary therapy.
Don't overread it
No interaction is not proof that combining vutrisiran with tafamidis adds benefit.
The statistics, in plain English
A high interaction P value means the treatment effect looked similar with and without each drug, but subgroup tests in a trial of 654 patients have limited power to detect a difference.
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