Patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) who were treated with eplontersen, a once-monthly transthyretin gene silencer, experienced no significant difference in cardiovascular mortality and recurrent cardiovascular events compared with those treated with placebo, according to results from the CARDIO-TTRansform trial presented at ESC Congress 2026 and simultaneously published in NEJM.

The trial, conducted in 130 centres in 20 countries, enrolled a total of 1,432 patients with wild-type or hereditary ATTR-CM and randomized them to to receive eplontersen (45 mg) or placebo by subcutaneous injection every four weeks. The average age of study participants was 72 years, nearly 10% were women and 57% were receiving stabiliser therapy at baseline.

Overall results showed no difference in cardiovascular mortality and recurrent cardiovascular events with eplontersen compared with placebo up to 140 weeks despite suppression of circulating serum transthyretin. Specifically, 381 primary endpoint events occurred among the 210 patients receiving eplontersen vs. 392 events among the 231 patients receiving placebo.

Despite not meeting the primary efficacy endpoint, researchers did note a nominal statistical difference in the number of primary composite endpoint events among a prespecified subgroup of patients who were not receiving stabiliser therapy at baseline.

"Primary results appeared to be influenced by baseline stabiliser use with no clear benefit in patients receiving background stabiliser therapy, while fewer primary endpoint events occurred with eplontersen in patients not receiving a stabiliser," said Mathew S. Maurer, MD, FACC, in presenting the findings.

Maurer and colleagues said their findings add to the data surrounding the evaluation of TTR-lowering treatment strategies in ATTR-CM, but stress that an unmet need still exists for new treatments to improve the prognosis of patients with ATTR-CM.

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: ESC Congress, ESC26, Amyloidosis, Cardiomyopathies