The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial

A phase 2 randomized trial of the microRNA inhibitor CDR132L did not show a significant effect on the structure or function of the left ventricle in patients with heart failure following a myocardial infarction. The findings, published May 10, 2026, in Nature Medicine and presented at the 2026 ESC Heart Failure Congress, indicate that while the treatment was well tolerated, it did not provide a statistically significant benefit over a placebo in the studied population.

The study focused on CDR132L, a synthetic antisense oligonucleotide designed to inhibit microRNA-132 (miR-132). MiR-132 is identified as a central regulator of adverse cardiac remodeling, the process by which the heart changes shape and function in response to injury, such as a heart attack. By blocking this regulator, researchers aimed to mitigate the progression of heart failure.

HF-REVERT Trial Design and Population

The trial, known as HF-REVERT, was a multinational, randomized, double-blind, and placebo-controlled study. A total of 294 patients were enrolled. To be eligible for the trial, patients were required to have a left ventricular ejection fraction (LVEF) of 45% or less within 14 days after their index myocardial infarction, as well as elevated N-terminal pro B-type natriuretic peptide levels.

Participants were randomized to receive one of three interventions: a 5 mg/kg dose of CDR132L, a 10 mg/kg dose of CDR132L, or a placebo. The treatment consisted of three intravenous doses administered at four-week intervals. All patients continued to receive guideline-directed therapy alongside the study drug or placebo.

The modified intention-to-treat population included 280 patients who received at least one dose of the study drug. This group consisted of 245 men and 35 women.

Clinical Outcomes and Endpoints

The primary endpoint of the HF-REVERT trial was the percentage change in the left ventricular end-systolic volume index measured at six months. While the data showed improvement in this measure across all groups, there was no significant difference between the CDR132L treatment groups (both the 5 mg/kg and 10 mg/kg doses) and the placebo group.

Researchers also tracked several secondary endpoints to assess the drug’s impact on heart function. These included:

• Left ventricular ejection fraction (LVEF)
• Global longitudinal strain
• N-terminal pro B-type natriuretic peptide levels

The results for these secondary endpoints were also not significantly different when comparing the CDR132L groups to the placebo group.

Safety and Exploratory Analysis

Despite the lack of efficacy in the primary and secondary endpoints, CDR132L was found to be well tolerated by the participants. The study reported no toxicity signals related to the heart, kidneys, liver, or hematologic system.

Prespecified exploratory analyses provided a potential avenue for future research. These analyses suggested that CDR132L treatment might offer benefits specifically for patients who exhibited advanced adverse remodeling at the start of the trial. This finding supports the continued evaluation of CDR132L, potentially including its application in chronic heart failure conditions.

The trial is registered under ClinicalTrials.gov identifier NCT05350969.