microRNA-132: Regulating Pathological Heart Remodeling After Heart Attack

Results from the first randomized trial evaluating the use of microRNA inhibition to treat heart failure were presented on May 10, 2026, at Heart Failure 2026, the annual congress of the Heart Failure Association of the European Society of Cardiology.

The trial investigated CDR132L, a synthetic antisense oligonucleotide designed to block microRNA-132 (miR-132). This specific non-coding RNA is implicated in the progressive adverse cardiac remodeling that often occurs after a heart attack, where the heart muscle enlarges excessively and the pumping function of the left ventricle is impaired.

The phase 2 trial, known as HF-REVERT, focused on patients with recent myocardial infarction and left ventricular systolic dysfunction. Within 3 to 14 days following a heart attack, 294 patients were randomized to receive either a 5 mg/kg dose of CDR132L, a 10 mg/kg dose, or a placebo.

The treatment consisted of three intravenous doses administered at four-week intervals, provided alongside standard guideline-directed therapy. A total of 280 patients, including 245 men and 35 women who received at least one dose, were included in the modified intention-to-treat population.

The primary endpoint of the study was the percentage change in the left ventricular end-systolic volume index at six months, which serves as a measure of heart remodeling. While this index improved across all study groups, there was no significant difference between the CDR132L treatment groups and the placebo group.

Secondary endpoints also failed to show a significant difference between the patients receiving CDR132L and those receiving the placebo. These measures included the left ventricular ejection fraction, global longitudinal strain, and N-terminal pro B-type natriuretic peptide.

Despite the lack of significant improvement in the primary and secondary endpoints for the general study population, the drug was reported to be well tolerated. Researchers found no toxicity signals related to the heart, liver, kidneys, or hematologic systems.

The trial included prespecified exploratory analyses that suggested CDR132L might offer potential benefits for a specific subset of patients—those who exhibited advanced adverse remodeling at the start of the study. These findings provide a basis for further evaluation of the therapy, including its potential application in chronic heart failure conditions.

The rationale for the study stems from a significant unmet need for treatments that target the underlying pathophysiological processes of heart failure. More than 55 million people globally live with heart failure, a prevalence that is increasing due to an aging population and improved survival rates following cardiovascular events.

Professor Johann Bauersachs of the Hannover Medical School in Germany, who presented the findings, noted the importance of targeting these processes.

Despite progress made in the treatment of heart failure, a major unmet need exists for treatments that directly target pathophysiological processes. MicroRNA-132 is a regulatory (noncoding) RNA that is implicated in the progressive adverse cardiac remodelling observed in heart failure.

Professor Johann Bauersachs, Hannover Medical School

Previous research in a phase Ib trial had suggested that CDR132L was associated with improvements in cardiac function. While the HF-REVERT phase 2 results did not mirror those findings for the broader group of patients early after a heart attack, research continues to determine if patients with left ventricular hypertrophy and chronic heart failure may benefit from the treatment.