CDR132L Fails to Improve Ventricular Volume After Myocardial Infarction

Adverse left ventricular remodeling after acute myocardial infarction remains a primary driver of heart failure, affecting nearly one-third of survivors despite modern reperfusion and guideline-directed therapies [1, 2]. While current treatments target neurohormonal pathways, attention has turned to epigenetic regulators like microRNA-132, a short, non-coding RNA molecule implicated as a central mediator of pathological cardiac hypertrophy and fibrosis [3, 4]. This has led to the development of therapies like CDR132L, an antisense oligonucleotide, which is a synthetic strand of nucleic acid designed to bind and inhibit a specific RNA target. The HF-REVERT trial was a phase 2 study designed to evaluate if inhibiting microRNA-132 with CDR132L could mitigate adverse remodeling [5, 6]. In 294 patients recently post-MI, three intravenous doses of CDR132L at 5 mg/kg or 10 mg/kg were compared to placebo. Despite a strong preclinical rationale [7, 8], the study found no significant difference at six months in its primary endpoint, the change in left ventricular end-systolic volume index, or in key secondary measures like ejection fraction and N-terminal pro B-type natriuretic peptide [5].