Comorbidity Burden in Transthyretin Amyloidosis With Cardiomyopathy

Q: What are the key findings of this study?

Vutrisiran consistently reduced the risk of all-cause death and recurrent cardiovascular events compared with placebo regardless of comorbidity burden.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (n=654). Intervention: Vutrisiran vs. Placebo. Primary outcome: Composite of death from any cause and recurrent cardiovascular events (RR 0.65, 95% CI 0.45-0.93).

Q: What does this research mean for the field?

The clinical benefits and safety profile of vutrisiran in transthyretin amyloidosis with cardiomyopathy are consistent regardless of baseline comorbidity burden. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Sarah Maria Birkhoelzer; Yasuhiro Hamatani; Karola Jering; Brian Lee Claggett; Muthiah Vaduganathan; Jan M. Griffin; Francesco Cappelli; Olivier Lairez; Julian David Gillmore; Marianna Fontana; Scott David Solomon

doi:10.1016/j.jchf.2026.103286

August 1, 2026JACC Heart FailureOpen Access

Comorbidity Burden in Transthyretin Amyloidosis With Cardiomyopathy

View Full Paper

Ask AI

Bookmark

Share

Key result

Vutrisiran cuts mortality and recurrent cardiovascular events ~35% vs. placebo, regardless of comorbidity burden.

RR 0.65
95% CI 0.45-0.93
n=654

Why the study?

The impact of comorbidity burden on morbidity, mortality, and treatment effect of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) was unclear.

Key Points

To assess how comorbidity burden, quantified by the Charlson Comorbidity Index, influences clinical outcomes and modifies the treatment efficacy and safety of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy.
Post hoc analysis of the randomized HELIOS-B trial evaluating 654 randomized and treated participants with transthyretin amyloidosis with cardiomyopathy receiving vutrisiran (25 mg subcutaneously) or placebo.
Participants were stratified into low (score 0-5; n=361) and high (score >5; n=293) comorbidity burden using the Charlson Comorbidity Index.
The primary composite endpoint was all-cause mortality and recurrent cardiovascular events, analyzed across comorbidity categories and continuously using Poisson regression.
A high comorbidity burden showed a weak relationship with the primary endpoint compared to low burden (HR: 1.21 [95% CI: 0.92-1.59]; HR per unit Charlson Comorbidity Index: 1.05 [95% CI: 0.96-1.16]).
Vutrisiran improved the primary outcome across groups, with rate ratios versus placebo of 0.65 (Q1-Q3: 0.45-0.93) in low comorbidity burden and 0.80 (Q1-Q3: 0.56-1.18) in high comorbidity burden (Pinteraction = 0.14).
Adverse events occurred less frequently with vutrisiran than with placebo regardless of baseline comorbidity burden, with no difference in adverse events between comorbidity categories.

Study Design

Type

RCT (n=654)

Randomization

Randomized

Multicenter

Yes

PICO

P

Population

654 patients with transthyretin amyloidosis with cardiomyopathy (mean age 75 years, 8% female) from the HELIOS-B trial, analyzed to assess the impact of comorbidity burden on vutrisiran treatment efficacy.

I

Intervention / Comparator

Vutrisiran vs Placebo (25 mg)

O

Primary Outcome

Composite of death from any cause and recurrent cardiovascular events — RR 0.65 (0.45-0.93)

Main Result

Relative Risk: 0.65 (95% CI 0.45–0.93)

Limitations

The CCI was designed for general medical populations and does not account for clinically relevant comorbidities specific to ATTR-CM.
The exclusion criteria of the HELIOS-B trial favored a patient group with a lower baseline risk profile by excluding patients with symptomatic CAD, active malignancy, eGFR <30 mL/min/1.73 m2, and NYHA class IV.
Because age is incorporated within the CCI, the independent effect of age and multimorbidity cannot be fully separated.
The CCI was designed to predict 1-year mortality alone, not CV events or treatment response, and may lack sensitivity for amyloid-specific outcomes.
This is a post hoc analysis of the HELIOS-B trial, which was not powered to detect treatment-effect heterogeneity by comorbidity and age.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Vutrisiran benefit appears consistent across comorbidity burdens in ATTR-CM; extends HELIOS-B but hypothesis-generating pending prospective confirmation.

Abstract

No abstract yet. The journal hasn't published one we can show.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Birkhoelzer et al. (2026) conducted an RCT in Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) (n=654). Vutrisiran vs. Placebo was evaluated on Composite of death from any cause and recurrent cardiovascular events (RR 0.65, 95% CI 0.45-0.93). Vutrisiran consistently reduced the risk of all-cause death and recurrent cardiovascular events compared with placebo regardless of comorbidity burden.

synapsesocial.com/papers/6ad0fc8615427f6a840401e2 https://doi.org/10.1016/j.jchf.2026.103286

View Full Paper

Ask AI

Bookmark

Share

Comorbidity Burden in Transthyretin Amyloidosis With Cardiomyopathy

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Comorbidity Burden in Transthyretin Amyloidosis With Cardiomyopathy

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading