Pharmacotherapy of cardiovascular diseases from herbs and pills to nucleic acids

Cardiovascular (CV) diseases continue to cause substantial morbidity and mortality. Risk factors are inadequately controlled, compliance with medication remains suboptimal, and treatments are not sufficient to fully prevent the progression of atherosclerotic CV disease, heart failure, arrhythmias, and valvular heart diseases. An increased understanding of the genetic basis of CV diseases and advances in the technology of therapeutics have led to the development of nucleic acid-based therapies (NATs) for prevention and treatment of CV risk factors and diseases. Nucleic acid-based therapies can target disease pathways at the translational level preventing the formation of disease-causing proteins that could not be effectively targeted by other pharmacological therapeutics and will likely improve treatment adherence by providing long-acting effects over many months rather than daily treatment. These therapies include RNA-targeted therapeutics, gene editing therapeutics, and gene therapies. Challenges around the use of NATs may be unique with each new drug and new target and may include long-term unanticipated side effects, and issues around specificity, targeting, and stability. Assessing NATs for marketing approval continues to pose challenges for regulatory agencies. These include their diverse nature, limited data on pharmacology, clinical safety and efficacy, and the lack of long-term results. Barriers in clinical practice may include the lack of specific education, fear of off target effects, costs, and ethical challenges. Implementation of these novel therapies will require careful patient selection and education. Despite potentially high treatment costs, possible long-term cost savings could result from fewer healthcare visits due to infrequent NAT administrations, and lower rates of disease progression, hospitalization, and CV events due to sustained improvement in control of disease pathways and risk factors.