Comorbidity burden in transthyretin amyloidosis with cardiomyopathy: insights from the HELIOS-B trial
S Birkhoelzer, Y Hamatani, K Jering, B Claggett, M Vaduganthan, J Griffin, F Cappelli, O Lairez, J Gillmore, M Fontana, S SolomonAbstract
Background
Patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) present with multiple comorbidities. Vutrisiran reduced morbidity and mortality in patients with ATTR-CM compared with placebo. Whether comorbidity burden affect the outcome of patients with ATTR-CM and impact the treatment effect of vutrisiran has not previously been investigated.
Methods
The Charlson Comorbidity Index1-3 (CCI) is a validated weighted index of 17 comorbidities and age, used to assess comorbidity burden. We aimed to investigate the impact of comorbidity burden in the HELIOS-B trial, which compared vutrisiran to placebo in ATTR-CM. The primary outcome was a composite of all-cause death and cardiovascular (CV) events. Patients’ demographics, outcomes, treatment effect, and adverse events were assessed in participants with low (CCI 0-5) and high (CCI >5) comorbidity burden and we assessed whether comorbidity burden modified the treatment effect of vutrisiran.
Results
Among 654 randomized and treated participants (age: 75±7 years; 8% women), CCI at baseline ranged from 1 to 12, with a mean CCI of 5.6 ±1.7; 361 (55.2%) participants had a low and 293 (44.8%) a high comorbidity burden. Participants with higher CCI were older (78±5 vs. 73±7 years), more commonly had wild-type ATTR (93 vs. 85%, p<0.001), and had higher NT-proBNP (2095 vs.1844 ng/L, p=0.003) than those with low CCI. Each increment of CCI was associated with a numerical, but non-significant increase in all-cause mortality and recurrent CV events (HR: 1.05, 95% CI, 0.96, 1.16, p=0.27). Vutrisiran consistently improved clinical outcomes across the spectrum of CCI for the primary endpoint (pinteraction=0.14) and death from any cause alone (pinteraction=0.54). Adverse events occurred more frequently in individuals with high comorbidity burden, but less frequently with vutrisiran than with placebo regardless of comorbidity burden.
Conclusion
The clinical benefits and safety profile of Vutrisiran were consistent regardless of the burden of co-existing conditions. Comorbidity burden alone should not influence treatment considerations for vutrisiran in eligible patients with ATTR-CM.For image description, please refer to the figure legend and surrounding text.