Key result
In a systematic review of 14 studies, RNAi therapeutics like patisiran and revusiran improved cardiac output and left ventricular wall thickness in patients with cardiac amyloidosis.
Why the study?
Heart failure is a leading cause of mortality, and RNAi interventions hold promise for patients resistant to conventional drugs due to off-target effects and lack of specificity.
Do RNAi therapeutics improve cardiac function and are they safe in heart failure?
Systematic Review (n=14)
Do RNAi therapeutics improve cardiac function and are they safe in heart failure?
RNAi therapeutics show promise in improving cardiac function in heart failure and cardiac amyloidosis, though they are associated with specific adverse effects requiring further evaluation.
May support RNAi use in cardiac amyloidosis; extends TTR evidence but leaves safety and HF efficacy unresolved.
BACKGROUND: Heart failure is a major worldwide health concern and leading cause of mortality. RNAi interventions hold promise for patients resistant to conventional drugs due to their off-target effects and lack of specificity. OBJECTIVES: To examine the safety and effectiveness of RNAi therapeutics in treating heart failure. METHODS: The PubMed, Embase, Scopus and Cochrane databases were searched using appropriate keyword from inception until December 31, 2023. A total of 14 studies fulfilling predefined selection criteria were included for qualitative synthesis. RESULTS: We found that in patients with cardiac amyloidosis, patisiran and revusiran showed considerable improvements in cardiac output and left ventricular wall thickness. In animal studies, Nox2-siRNA showed effectiveness in regaining heart function. Furthermore, cardiomyocyte count and left ventricular function were improved by DUSP5 siRNA + T3 therapy and meg3 inhibition after myocardial infarction (MI). RNAi showed minimal adverse effects like peripheral neuropathy, hepatotoxicity, urinary tract infection, vaginal infection, diarrhea, abdominal pain arrhythmias, conduction disorders, and cardiotoxicity (LV wall thinning, heart failure) and improved cardiac biomarkers. CONCLUSION: RNAi therapeutics are novel treatment option for improving cardiac function because their high target specificity, ability to target genes that conventional drugs struggle to reach and potential for long-lasting effects. Further research on optimizing delivery methods, improving target specificity, evaluating long-term safety profiles and cost-effectiveness to fully realize their potential.
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Saddique et al. (2024) conducted a systematic review in Heart failure (n=14). RNAi therapeutics was evaluated on Safety and effectiveness (cardiac output, left ventricular wall thickness, heart function). In a systematic review of 14 studies, RNAi therapeutics like patisiran and revusiran improved cardiac output and left ventricular wall thickness in patients with cardiac amyloidosis.
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