RNA therapeutics in cardiovascular treatment: a systematic review on clinical outcomes

Abstract

Cardiovascular diseases (CVDs) are the number one cause of death around the world, and there is a critical demand for new and efficient therapeutic strategies. In the last decade, RNA-based drugs, such as mRNA, miRNA, siRNA, have become an effective therapeutic approach. These treatments are directed at the root cause of disease or molecular origins of disease and are a more personalized and precise form of treatment than conventional medicines. The objective of this systematic review was to assess the clinical use of RNA-based treatments for cardiovascular disease in current studies. It also reviews the methods applied in this field of study, highlights areas that have gaps or in need of research and describes future research directions that would benefit from the RNA based therapies. We searched the studies in the PubMed, ScienceDirect, and Google Scholar databases for RCTs mentioning the use of RNA-based treatments for cardiovascular diseases and their publication year was between 2015 and 2025. Selection criteria Based on the PRISMA guide, studies were considered for inclusion. The RCTs involved hypertension, atherosclerosis, myocardial infarction, and heart failure. We collected data on treatment methods, RNA delivery systems, results, and side effects from each study. Cochrane Risk of Bias 2.0 was used to evaluate the risk of bias. This systematic review includes six RCT studies that were done on humans. The findings highlight the therapeutic potential of RNA-based treatments, especially the siRNA drug Inclisiran, which effectively lowers cholesterol by targeting the PCSK9 protein. miRNA therapies were found to influence cardiac changes in hearts in a way that modulates fibrosis and inflammation, while mRNA therapies showed promise in regenerating damaged heart tissue. Among these, Inclisiran stands out for its clinical efficacy and improved patient adherence due to its dosing regimen. But a number of included studies were at moderate to high risk of bias in terms primarily of insufficient randomisation, lack of blinding, incomplete data reporting and small size. These hold limit the integrity and long-term stability of current results. Future developments in the field of RNA therapy should also focus on the specific disease-related genes or proteins as a more effective treatment for cardiovascular diseases. Although the results are encouraging, limited data, well-designed RCTs, ideal delivery systems, and long-term follow-up evaluations.RNA therapeutics merged with personal genomic information could revolutionize the future of cardiovascular therapy opportunity to target CVD gene mutations directly and gene regulatory analyses, coupled to a patient’s genomic profile can offer a more comprehensive understanding of an individual patient’s phenotype and how it responds to therapy.