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NHS to pioneer cholesterol-busting jab

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Dr Alexander Lyon, Consultant Cardiologist at The Physicians’ Clinic, discusses a new development in the treatment of cholesterol:

This BBC News story highlights a very exciting new development in the treatment of cholesterol to reduce the risk of heart disease. Doctors have known for many years that a high levels of unhealthy LDL cholesterol in the blood is a major cause of coronary artery disease which leads to heart attacks, heart failure following heart attacks and sudden death. Statins have been the cornerstone of treating cholesterol for over 20 years, which many research trials proving that statins reduce the risk of future heart attacks, strokes from carotid artery disease, and ultimately improve survival in people with coronary artery disease. However approximately half of people either cannot tolerate the higher doses of statins required, or have side effects and cannot take any statin, and continue to have high cholesterol levels driving their coronary disease.

Recently a new approach to block a protein called PCSK9 has been effective, as reducing PCSK9 appears twice as potent as statins at lowering cholesterol. We now recommend and prescribe a fortnightly PCSK9 antibody treatment which is injected under the skin to lower unhealthy LDL cholesterol in people who have a either established coronary artery disease or who are at high risk of coronary disease but who either cannot take any statin, or whose cholesterol is not perfectly controlled by their statin therapy, and therefore still have a high LDL cholesterol and increased risk of a future heart attack.

We are now in a new era in cardiovascular risk management with the development of new inhibitory RNA therapies called siRNAs which block the production of the PCSK9 protein. This effect of reducing PCSK9 protein production is in contrast to the antibodies which block the PCSK9 protein action once it has been made in the liver. siRNAs are genetic therapies as RNA contains the genetic code from DNA genes first described by Watson and Crick, and siRNAs are able to block the RNA molecules which drive protein production. The amazing observation from the recent research trial is that a single injection of one these new siRNA targeting PSCK9 called Inclisiran can reduce the PCSK9 protein levels in people for at least 6 months, and this leads to a reduction in LDL cholesterol which was also maintained for 6 months. Therefore this new cholesterol-lowering treatment was studied as a treatment delivered once every 6 months and it maintained effective cholesterol control over the 12 months studied with just 2 injections. Inclisiran treatment appears safe so far, particularly in people who has side effects from statin treatment, but it is early days, and longer follow up in the research trials is required to ensure that long term treatment with these new genetic therapies remains safe as they are potentially a lifelong treatment.

These new siRNA therapies targeting PCSK9 including Inclisiran are undergoing review by the regulatory authorities but are not currently licensed and available, whereas the PCSK9 antibody therapies are available and in my experience are effective and well tolerated without many side effects. Inclisiran increases the armamentarium of treatments now available to cardiologists to help reduce the risk of heart attacks and other complications of coronary artery disease, and opens up a new era where we evolve cholesterol therapies from a daily tablet therapy (statins), to fortnightly PCSK9 antibody injections and now twice yearly PCSK9 siRNA injections. Therefore, in the future, coming to a cardiology clinic for a cholesterol therapy injection once every 6 months may be the best and most convenient treatment to reduce risk of heart attacks.

Please follow this link to read the news article

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