Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled clinical trial
PubMed 36528793 · doi:10.1016/j.ymthe.2022.11.017
What was done
In the randomized, double-blind EPICCURE trial, 11 patients with left ventricular ejection fraction (LVEF) of 30%–50% undergoing elective coronary artery bypass grafting (CABG) were randomized to receive 30 direct epicardial injections of naked VEGF-A mRNA (AZD8601, 3 mg total; n=7) or placebo (citrate-buffered saline; n=4). Injections were targeted to ischemic but viable myocardium mapped using quantitative [15O]-water positron emission tomography, with follow-up through 6 months.
What was found
Over 6 months, no deaths, treatment-related serious adverse events, infections, immune reactions, or arrhythmias were observed in the AZD8601 group. The abstract notes exploratory indications of potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and NT-proBNP levels, but reports no specific numerical effect sizes, confidence intervals, or p-values.
Why it matters
This represents the first clinical test of direct, unencapsulated naked mRNA delivery to human myocardium, establishing initial procedural safety and feasibility for cardiac gene therapy.
Limits
The sample size is very small (n=11 total, 7 active vs. 4 control), precluding any statistically meaningful assessment of efficacy. The abstract reports no quantitative values for any of the exploratory functional or biomarker outcomes, and follow-up was limited to 6 months in a select surgical population.
Cited by
- supports In 2017, clinical trials took place testing an mRNA-based vaccine for influenza and injecting mRNA into the heart to treat heart failure.