RNAi therapeutics improve ATTR amyloidosis with cardiomyopathy survival, functionality
Key takeaways:
- RNA therapeutics lowered all-cause mortality, increased 6-minute walk distance and improved quality of life.
- RNA therapeutics also decreased brain natriuretic peptide levels and global longitudinal strain.
CHICAGO — RNA therapeutics improved survival, 6-minute walk distance and quality of life for patients with transthyretin amyloid cardiomyopathy, according to study results presented at the American College of Cardiology Scientific Session.
“Newer RNA interference therapeutics, patisiran and vutrisiran, show significant promise as an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM),” Farhan Naeem, MD, from the department of cardiology at Massachusetts General Hospital and Harvard Medical School, told Healio. “RNA interference therapy reduces mortality, increases 6-minute walk distance and enhances quality of life in ATTR-CM patients leading to better survival and functionality. It significantly lowers brain natriuretic peptide levels and improves global longitudinal strain, indicating reduced cardiac damage and disease progression. It provides clinical benefits without increasing adverse or serious cardiac events.”
Naeem and colleagues searched PubMed, Cochrane Central, Scopus, Embase and ClinicalTrials.gov and identified four studies comparing RNA interference therapeutics to placebo in a total of 1,179 patients with ATTR-CM. Primary outcome was all-cause mortality, 6-minute walk test and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS).
Compared with placebo, researchers linked treatment with RNA interference therapeutics with significantly lower all-cause mortality (OR = 0.65; 95% CI, 0.45-0.83), longer 6-minute walk test distance (median difference = 19.66; 95% CI, 13.36-25.97) and higher KCCQ-OS (median difference = 4.78; 95% CI, 2.31-7.24).
In addition, patients treated with RNA interference therapeutics experienced a decrease in brain natriuretic peptide levels and global longitudinal strain. However, change in left ventricular wall thickness was similar between treatment with RNA interference therapeutics and placebo.
Researchers observed no significant differences in adverse event or serious adverse event occurrence between the two groups.
“Large high-power randomized controlled trials assessing efficacy across ATTR-CM variants, hereditary vs. wild-type, and NYHA functional classes are needed to further confirm these findings, strengthen the evidence base and to identify which patients would benefit the most,” Naeem said.
For more information:
Farhan Naeem, MD, can be reached at farhannaeem1231@gmail.com.
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Kidess GG, et al. Efficacy and safety of RNA interference therapeutics in patients with transthyretin amyloidosis cardiomyopathy. Presented at: American College of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid meeting).