Conference Coverage

RNA Therapeutics Improve Survival, Reduce Cardiac Failure in Transthyretin Amyloidosis

Edited by:
Anthony Calabro, MA

Key Highlights

  • RNA therapeutics significantly reduced all-cause mortality compared with placebo in transthyretin amyloidosis.
  • Treatment was associated with a lower risk of cardiac failure.
  • Patients receiving RNA therapeutics experienced significant improvements in neuropathy impairment and quality-of-life scores.
  • Small interfering RNAs demonstrated greater improvement in neuropathy scores than antisense oligonucleotides.

Research presented at the American College of Cardiology’s Annual Scientific Session, held March 28–30, 2026, in New Orleans, LA, suggests RNA therapeutics significantly improve survival and cardiovascular outcomes in patients with transthyretin amyloidosis (ATTR). In a meta-analysis of randomized controlled trials, investigators reported reductions in all-cause mortality and cardiac failure risk among patients treated with RNA-targeting therapies compared with placebo.

ATTR is a progressive disease caused by the deposition of misfolded transthyretin protein, leading to cardiomyopathy, neuropathy, and multi-organ dysfunction. RNA therapeutics, including small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs), target hepatic production of transthyretin and represent a disease-modifying strategy for both hereditary and wild-type ATTR.

Investigators conducted a systematic search of PubMed, the Cochrane Library, and Embase through April 2025 to identify randomized controlled trials comparing RNA therapeutics with placebo in patients with ATTR. Outcomes assessed included all-cause mortality, cardiac failure, modified Neuropathy Impairment Score +7 (mNIS+7), Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QOL-DN) score, modified body mass index (mBMI), and adverse events.

Data from eligible trials were pooled using random-effects models. Subgroup analyses were performed to compare therapeutic classes, including siRNAs and ASOs.

Study Findings

The meta-analysis included 6 randomized controlled trials involving 1,813 patients, including 1,033 treated with RNA therapeutics and 780 receiving placebo. Treatment with RNA therapeutics was associated with a significant reduction in all-cause mortality (RR, 0.69; 95% CI, 0.53–0.90; P = .007; I²=0%). RNA therapies also significantly reduced the risk of cardiac failure (RR, 0.79; 95% CI, 0.67–0.94; P = .006; I²=0%).

Neurologic outcomes also improved in patients receiving RNA therapeutics. Treatment significantly improved mNIS+7 scores compared with placebo (SMD, −1.35; 95% CI, −1.76 to −0.94; P < .001; I²=81%) and Norfolk QOL-DN scores (SMD, −0.89; 95% CI, −1.11 to −0.67; P < .001; I²=39%). Subgroup analysis showed that siRNAs demonstrated greater improvement in mNIS+7 scores than antisense oligonucleotides (P < .001). Additionally, RNA therapeutics significantly preserved modified body mass index (SMD, 0.82; 95% CI, 0.21–1.43; P = .008; I²=94%).

Safety outcomes were comparable between treatment and placebo groups. The risk of adverse effects (RR, 1.00; 95% CI, 0.98–1.01; P = .51; I²=0%), serious adverse effects (RR, 0.91; 95% CI, 0.79–1.04; P = .16; I²=20%), and cardiac adverse events (RR, 0.89; 95% CI, 0.79–1.01; P = .06; I²=26%) did not significantly differ between groups.

Clinical Implications

According to the study authors, these findings suggest RNA therapeutics significantly improve survival and reduce cardiac failure risk in patients with transthyretin amyloidosis while also improving neurologic outcomes and quality of life. The authors indicated that RNA-based therapies may represent an important disease-modifying approach for ATTR cardiomyopathy and neuropathy.

Expert Commentary

“RNA therapeutics significantly improve survival and reduce cardiac failure in ATTR while also providing substantial neurological benefits with a favorable safety profile,” the researchers concluded. “These findings underscore RNA-based therapies as transformative for ATTR cardiomyopathy and neuropathy, crucial for reducing morbidity and mortality.”

Reference
Sajjad M, Chaudhry WR, Hasan SU, Ijaz H, Hussain A, Wazir H, et al. Efficacy and safety of RNA therapeutics in transthyretin amyloidosis: a meta-analysis of randomized controlled trials. Presented at: American College of Cardiology Annual Scientific Session; March 28–30, 2026; New Orleans, LA. https://accscientificsession.acc.org/