About 70 per cent of patients admitted to National Heart Centre Singapore (NHCS) with heart attacks have unhealthy low-density lipoprotein (LDL) or bad cholesterol levels.

After a heart attack, doctors typically start them on high doses of statins. These are drugs proven to save lives and prevent deaths by reducing both inflammation in coronary arteries and recurrent heart attacks.

However, after a year on statins following a heart attack, one in two on the medication still cannot reach target cholesterol levels, said Dr Jack Tan, Deputy Head and Senior Consultant, Department of Cardiology, NHCS.

This led Dr Tan to start giving two new drugs – alirocumab or evolocumab – to patients. The drugs were approved by the Health Sciences Authority last year for use on people who have had a heart attack, or are at a high risk of one. These are patients who cannot reach their target levels while on conventional treatment, or cannot tolerate the usual high-intensity statins.

The drugs have had positive data from a worldwide study that also included participants from Singapore.
Alirocumab was found to be much more effective in reducing LDL levels than high-dose statins, while having barely any side effects, said Dr Tan, who is also Adjunct Assistant Professor, Duke-NUS Medical School.

Made by different companies, both alirocumab and evolocumab act similarly. They target and inhibit a protein called PCSK9, which prevents the breakdown of LDL receptors in the liver. These receptors remove harmful LDL cholesterol from the blood.

Who are these drugs for?

Currently, NHCS has 20 patients on either one of the two new drugs. They are those at high risk of a heart attack, who cannot tolerate high-dose statins, or have not been able to reach target levels. Alirocumab is prescribed in two doses (no difference in price), and evolocumab in a standard dose. Bothare taken once a fortnight through subcutaneous injections.

Except for patients who cannot tolerate statins, Dr Tan said the preferred way to use both drugs is in combination with a statin, because they complement statins and produce better results when paired up. He said they complement statins in treating patients who are at a high risk of a heart attack but cannot reach target LDL cholesterol levels with statins alone.

The drugs are also given to people with an inherited condition called homozygous familial hypercholesterolemia, where the bad cholesterol is so high that even the strongest doses of statins cannot reduce it to target levels.

One in 300 to 500 people have this condition in the milder heterozygous form. “From young, their baseline
cholesterol is very high. So they have heart attacks earlier in life. If their condition is more severe, they can have heart attacks as young as in their 20s because their cholesterol is sky-high,” said Dr Tan.

Patients have two considerations regarding the drugs: cost, and that the drugs have to be injected, which some find off-putting, although the jabs are convenient and almost painless.

One month’s treatment with alirocumab or evolocumab is about $600 at NHCS, as subsidies are not available for these non-standard drugs. Comparatively, the high dose of the generic statin, atorvastatin, costs $18 per month before subsidy, and $4.50 on a 75 per cent subsidy.

Side effects of statins

Statins work for the majority of patients with high cholesterol, but some people suffer side effects.

These include myalgia (muscle pain) and fatigue. In very rare cases (less than 3 per cent of patients), it can cause liver abnormalities. Rarer still is that less than one in a thousand develop rhabdomyolysis, where muscles die, causing the kidneys to fail.

Dr Tan said doctors usually do blood tests for patients within the first three months of prescribing statins to see if the drugs are working, and to check for side effects. The tests look into liver enzymes, kidney function and the lipid cholesterol panel.

“Side eff ects are uncommon. For liver failure to result from statins is very rare, but to cause a bit of enzyme rise is not uncommon, so when we see that, they’d be classified as statin-intolerant. This means they have side effects from statins, and we can’t push up the dose anymore.”

Try lifestyle changes first

Doctors recommend lifestyle changes as the first line of defence to attain healthier LDL cholesterol levels, said Dr Tan.

While how much LDL the body produces is largely predetermined by a person’s genes, diet is still important.

“If you eat bad, oily food and have the bad genes, it’s doubly worse,” said Dr Tan. He advised cutting back on meat and oily and processed food, and moving towards a plantbased diet to help bring LDL cholesterol to healthier levels.