High cholesterol is relatively common and there are many ways to go about trying to reduce the amount of cholesterol and other lipids in the blood, consisting of both pharmacological approaches and lifestyle changes. Though controversial, the most widely used approach, used in combination with diet and exercise, is statin therapy. However, there are many other treatments available to help manage cholesterol in order to prevent more serious health events such as myocardial infarction or stroke. In addition to the mainstays, research is ongoing into alternative options, particularly for the benefit of those people who are having little success with existing approaches.
New approval
Recently approved by the National Institute for Health and Care Excellence (NICE), inclisiran may be a ‘game changer’ for people who have previously had a heart attack or stroke. NICE (2021) issued guidance on the 1 September that recommended the new anti-cholesterol drug, inclisiran (Leqvio, Novartis), for people with primary hypercholesterolaemia or mixed dyslipidaemia, who have already had a cardiovascular event such as a myocardial infarction or stroke.
The decision follows an agreement between drug company, Novartis, NHS England and NHS Improvement, making inclisiran available at a discount for an undisclosed amount. The drug comes as an injection and would only need to be administered twice a year. Those with hypercholesterolaemia who have had a previous cardiac event would be eligible for this new drug, with the aim of preventing another event. Inclisiran can be used on its own or alongside statins, or other cholesterol-lowering drugs.
What is incliseran?
Inclisiran is the first of its kind of a new cholesterol-lowering treatment, with pharmacokinetics that differ from traditional methods of treatment. It uses RNA interference (RNAi) to boost the liver's ability to remove harmful cholesterol from the bloodstream (NICE, 2021).
Patients with primary hypercholesterolaemia and those who have dyslipidaemia are known to be at higher risk of cardiovascular events. The current system in the UK encourages patients to incorporate dietary changes, statins and other medications that help to lower cholesterol, either alone or in combination. The trial evidence has revealed that this new treatment may help to reduce cholesterol when these other methods have failed, demonstrating its potential efficacy in a situation where such an alternative mode of action would be beneficial and possibly even lifesaving.
However, there are no data currently to directly compare inclisiran with other treatments such as ezetimibe, alirocumab or evolocumab and there is no long-term evidence at present that shows inclisiran's long-term efficacy on cardiovascular outcomes (NICE, 2021). However, inclisiran is considered by NICE (2021) to be a cost-effective measure for people who have previously had a cardiovascular event and whose cholesterol levels remain high following the maximum tolerated lipid-lowering therapy being offered. The cost-effectiveness estimates remained uncertain for those who have never actually had a cardiovascular event but were thought to likely be above what NICE would deem an acceptable use of NHS resources. A clinical trial is planned that will analyse whether inclisiran can reduce the risk of cardiovascular events in this population (NICE, 2021).
Meindert Boysen, NICE deputy chief executive and director of the Centre for Health Technology Evaluation said: ‘Inclisiran represents a potential game-changer in preventing thousands of people from dying prematurely from heart attacks and strokes. We're therefore pleased to be able to recommend it as a cost-effective option on the NHS supported by the ground-breaking deal between NHS England and NHS Improvement and Novartis - a deal that could see as many as 300 000 people with high cholesterol or mixed dyslipidaemia who have already had a previous cardiovascular event receive the drug over the next 3 years.’
According to Novartis, the approval is based on the results of the robust ORION clinical development programme, where the researchers found that Leqvio (inclisiran) provided an effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction of up to 52% in patients with a raised level of LDL-C, despite having the maximum amount that can be given of statin therapy. Following the first dose, the second dose would be at 3 months but further doses would then be at 6-month intervals. The idea is that once treatment has started, long-term adherence can be maintained.
Inclisiran works by providing a sustained and effective reduction in LDL-C for patients specifically with atherosclerotic disease, atherosclerotic cardiovascular disease risk equivalent patients, and those with heterozygous familial hypercholesterolaemia (HeFH) (Novartis, 2021).
Non-pharmacological solutions
It is important however that, societally, we do not become completely dependent on pharmacological approaches alone. Dietary modification is important, especially where saturated fat is concerned. Many people do not realise the differences found in fats they consume and swaps can be recommended. For example, butter could be swapped to vegetable oil spreads such as sunflower, olive or rapeseed oil spreads, whole milk could be switched to skimmed milk, natural yoghurt can be used as an alternative to sour or double cream, and mince could be switched to eating leaner, lower-fat options (British Heart Foundation (BHF), 2021). Red or processed meat could be swapped for fish, turkey or chicken, consumed without the skin, or plant-based proteins such as lentils could be eaten instead of meat. The BHF (2021) also recommends heart-healthy options as comfort foods, to replace takeaways.
Eating more fibre can also reduce cholesterol as fibre can reduce the amount of cholesterol taken up by the bloodstream from the intestine. To incorporate more fibre, patients can consume at least five portions of fruit and vegetables each day, as they have a higher fibre content and many nutrients. Pulses such as lentils, beans and chickpeas as well as oats and seeds also contain fibre, as well as whole-grain choices of bread or pasta rather than refined white options.
Exercise of course can be a social prescribing task. The patient could be encouraged to use the stairs rather than the lift, and to take a brisk instead of a slow walk. They could do 2-minute bursts of jumping jacks several times a day. For patients who are unable to leave their homes, yoga and Pilates are both good options and the BHF (2021) website offers other recommendations as well.
Smoking and alcohol consumption are also significant factors in high cholesterol. Smoking raises the bad cholesterol while lowering the good cholesterol thus increasing the risk of myocardial infarction and stroke. For smoking cessation, the patient can be referred via their GP to various stop smoking services, or the patient can call the service directly themselves in England. Other free services exist across the rest of the UK. The patient can then learn how to manage cravings and gradually cut down or stop altogether. By reducing alcohol intake, the liver will be able to work better at getting rid of the bad cholesterol and can improve the health of the heart by helping the patient to maintain a healthy weight and reduce their blood pressure. If someone does not want to cut out alcohol completely, they can be recommended to drink less than 14 units a week, have a few days each week where they do not drink at all, avoid binge drinking by halving the amount usually consumed, and ordering smaller drinks.
Conclusion
Not all patients have the same needs or the same success with all therapies or approaches. Some patients may also have more complex needs and even dual diagnoses. Having more options from which to personalise treatment, using a combination of pharmacological and non-pharmacological approaches and ensuring that mental, as well as physical, health are nurtured can provide the most balanced and patient-centred approach. Being mindful of drug dependance and addiction, as well as developing an awareness regarding making appropriate referrals to local addiction and other services such as improving access to psychological therapies (IAPT) are also essential pieces of the puzzle. Such a holistic approach can help to ensure that patients are effectively supported to make appropriate and informed therapy choices, self-manage their physical health by making healthier choices on a daily basis, developing the confidence and strength to exercise more, maintain a healthy body and lower their cholesterol as a result.