DO NOT despair if your bad cholesterol (also termed as low density lipoprotein or LDL cholesterol) remains in the high risk zone despite your best efforts at lifestyle changes. There are effective options to reduce your LDL cholesterol and, hence, your risk of heart attacks and stroke.

Reducing cholesterol production

The first-choice cholesterol-lowering drug will almost invariably be a statin. Statins act by inhibiting an enzyme, which is critical for cholesterol production. The Internet is rife with many anti-statin posts by individuals who give comments without any substantiated facts. In this era of social media, let your decisions be guided by facts and not baseless opinions.

Hence, you can take comfort in the fact that multiple large studies have shown that statins, by reducing LDL cholesterol, are able to reduce the incidence of heart attacks and strokes. Depending on the type of statin and the dosage used, the LDL cholesterol level can be reduced by 50 per cent or more.

Checklist before you take the pill

Although statins are widely prescribed, they are unsuitable for some individuals. Therefore, before you commence taking statins, you should go through this checklist of contraindications. Do not take statins if you are pregnant, planning for conception or breastfeeding. If you have severe liver disease, you should avoid statins. For those with impaired kidney function, dose adjustments may be necessary. For the elderly, caution must be taken if there is a family history of muscle aches with statins or high alcohol intake, as there is a higher risk of getting severe muscle pain. If you are uncertain, have a discussion with your physician. 

Statin side effects

Generally, low- to moderate-dose statin therapy is safe, and side effects are uncommon. Even with high-dose statins, the incidence of side effects is low, consisting mainly of muscle aches and a rise in liver enzymes. There is a small risk of developing diabetes mellitus with high-dose statin therapy. But the benefits obtained through a reduction in heart attacks and strokes in high-risk patients far outweigh the possible adverse effects of a small increase in the incidence of diabetes. Uncommon side effects of high-dose statins include reversible acute memory impairment and transient kidney protein leaks, which can be reversed with statin cessation or a lowering of the statin dose. 

Indications for stopping statins 

If you have started taking statins, there are two situations in which you may have to stop taking them. If there is severe elevation of your liver enzymes (three times higher than normal) or severe elevation of your muscle enzymes (greater than three to 10 times the upper limit of the normal range) with muscle ache, you should stop your statin medication and consult your doctor.

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Block the cholesterol in your food

There will always be those on a low to moderate statin dosage who cannot keep their cholesterol down as they are unable to resist the temptations of their favourite foods. Instead of increasing to a high-dose statin regime, there is the option of taking ezetimibe, a lipid-lowering agent that blocks the intestinal absorption of cholesterol and related plant sterols.

Ezetimibe alone can reduce LDL cholesterol by about 18 per cent and this effect is similar to doubling the dose of the statin three times (for example, it is equivalent to increasing 10 mg simvastatin to 80 mg). It is also an alternative for those who are unable to tolerate the side effects of statin.

Cholesterol “marvels”

In recent years, a new generation of cholesterol-lowering drugs has taken us to new lows in LDL cholesterol, which we have never achieved before. These new cholesterol “marvels” have helped us understand the concept that “the lower the LDL cholesterol, the better”.

The first generation of this new therapy (antibodies called PCSK9 inhibitors) work by increasing the availability of LDL cholesterol receptors (binding sites) that “capture” LDL cholesterol, thereby increasing the efficiency of LDL cholesterol removal from the blood circulation. This results in a reduction of LDL cholesterol by an average of 60 per cent. They are administered subcutaneously, fortnightly or monthly.

More recently, there is a newer therapy (called inclisiran) targeting the PCSK9 protein, which is able to reduce the LDL cholesterol by more than 50 per cent. The main advantage of inclisiran over the PCSK9 inhibitors (alirocumab and evolocumab) is that, at a steady state, it is administered at a six-monthly interval compared to a fortnightly or monthly injection for PCSK9 inhibitors.

These new cholesterol “marvels” are very effective drugs that can reduce LDL cholesterol and cardiovascular events on top of statin and/or ezetimibe treatment. Importantly, they are not only highly effective but also have a good safety profile. Hence, for those high-risk individuals who are unable to achieve recommended levels of LDL cholesterol or are intolerant to oral medication, these new injectable cholesterol “marvels” provide more options for the reduction of heart attack and stroke risk.

This new class of drugs is also a godsend for those who have inherited cholesterol disorders (familial hypercholesterolaemia) with stubbornly high LDL cholesterol levels that cannot be brought down to optimal levels with oral medication. Those with these genetic disorders have a higher risk of heart disease and early death. The new class of injectable cholesterol-lowering drugs provides an option for them to bring their LDL cholesterol levels to optimal levels.

Tips for treatment

Where lifestyle measures fail to help you achieve your target LDL cholesterol level, statins are usually the first-choice drugs prescribed by doctors. Go through the checklist first before you begin treatment. If there are no contraindications, start on a low to moderate dose of statin first. Side effects are uncommon at such doses and present mainly as muscle aches or elevated liver enzymes.

If the LDL cholesterol level remains stubbornly high, your doctor may either increase the dose of statin or add ezetimibe to the statin. If, despite being on your maximally tolerated dosage of statins and ezetimibe, your LDL cholesterol cannot be brought to an optimal level, your physicians may administer the new generation of injectable cholesterol-lowering agents to achieve optimal levels of cholesterol. Although injectable cholesterol-lowering drugs are highly effective and safe, they are more costly, and hence, oral medication is usually prescribed.

Lowering the LDL cholesterol to optimal levels remains the single most important and effective measure to reduce the risk of heart attack and stroke. The newest guidelines on lowering cholesterol to prevent heart disease are focused on lowering LDL cholesterol and are guided by the paradigm “the lower the LDL cholesterol, the better”.

Hence, by optimising your LDL cholesterol level, you can reduce the risk of cardiovascular death, which ranks as one of the top causes of death in modern societies. Eventually, when the cost of injectable cholesterol-lowering drugs drops significantly, and they are cost-effective for mass market use, they may be able to solve the problem of poor compliance with oral medication, provide significant LDL cholesterol-lowering with minimal risk of side effects, and result in a utopia where heart attacks become a rarity.

This article is part of a monthly series on health and well-being, produced in collaboration with Royal Healthcare