Heart and circulatory diseases are responsible for a quarter of all deaths in the UK, and make up the largest single cause of premature death in deprived areas (NHS England, 2019). It is sensible, then, that the NHS Long Term Plan (NHS England, 2019), which was published last year and set out the Government's priorities and plans for the coming decade, dedicated an entire chapter to actions designed to tackle cardiovascular disease (NHS England, 2019).
By focusing on prevention through lifestyle changes, early detection and treatment, cardiac arrest recognition and training in cardiopulmonary resuscitation (CPR) and cardiac rehabilitation, the NHS is seeking to prevent 150 000 myocardial infarctions, strokes and cases of vascular dementia over the next 10 years (NHS England, 2019).
There are many exciting developments taking place in genetics at present. This article explores some new experimental research in gene-silencing, which will undoubtedly transform the cardiovascular treatment landscape in due course.
As part of the NHS targets set out in the Long Term Plan (NHS England, 2019), a new unlicensed drug for people already living with cardiovascular disease is slated to be made available to patients by 2021, by NHS England in collaboration with the National Institute for Health Research, Oxford University and the pharmaceutical company, Novartis (Pharmaceutical Journal, 2020).
Provided through bi-annual injection, incliseran is a gene-silencing therapy that is expected to rapidly reduce low-density lipoprotein (LDL) cholesterol, potentially halving levels within a matter of weeks according to trials presented at the European Society of Cardiology (ESC) Congress last year in Paris (Gallagher, 2020). Incliseran is designed to control the instructions the body receives by silencing the PCSK9 gene. The PCSK9 protein binds to LDL receptors, targeting them for degradation. Incliseran is a small interfering RNA molecule that reduces PCSK9 production in the liver. With less circulating PCSK9, more LDL receptors are present on cell surfaces, enabling better clearance of LDL from the blood (Gallagher, 2020).
Despite incliseran not having the necessary approvals, it will be made available to patients later this year through a large-scale phase 3 clinical trial in UK patients that is being called ‘ground-breaking’ by the NHS (Gallagher, 2020). Patients at high risk of experiencing a myocardial infarction or stroke but who have not yet had one will be invited to participate in the trial, and it is estimated that approximately 40 000 people may be eligible (Gallagher, 2020).
Incliseran and associated evidence from previous trials will also be assessed via the regulatory approval programme of the National Institute for Health and Care Excellence (NICE), with the aim of an agreement for its more routine use at the population level then being made between NHS England and Novartis (Pharmaceutical Journal, 2020). It will be used as a preventative ‘add-on’ treatment to statins to reduce the risks of existing cardiovascular disease and should be available to the wider population by 2021 (Gallagher, 2020; Pharmaceutical Journal, 2020).
Statins, although at times controversial, remain a cornerstone cardiac medicine; however, some people may be on the wrong type of statin, forget to take their medication or not adhere to their medicine for various reasons (Gallagher, 2020). Even when on statins, the LDL levels of many patients remain at dangerously high levels (Gallagher, 2020). In fact, a study published last year in the British Medical Journal concluded that, after 2 years of taking statins, half of patients in the general population do not achieve optimal lowering of their LDL cholesterol, which is 40% as per NICE (2016) guidelines, and will as a result experience significantly increased risk of future cardiovascular disease events (Akyea et al, 2019).
These are the patients for whom an injection of incliseran every 6 months may make all the difference. The therapy is expected to prevent 55 000 myocardial infarctions and strokes every year and, according to the Department of Health and Social Care and health secretary, Matt Hancock, could save 30 000 lives over the next 10 years (Gallagher, 2020). The first gene-silencing treatment, patisiran, was approved by NHS England last year to treat a form of amyloidosis, an abnormal buildup of amyloid protein in the body, which is rare but can cause serious symptoms (Gallagher, 2019).
Conclusion
The gene-silencing research outlined in this article is just some of the innovative work taking place in cardiovascular medicine. Next month's column will discuss tissue engineering and regeneration, with the use of heart patches, and the potential for self-repairing hearts. Each of these therapies holds promise for patients living with heart failure, which can have a devastating impact upon a person's quality of life and which is ultimately fatal despite improved outcomes.