A new, oral drug that effectively lowers cholesterol looks set for clinical approval. The latest trials of the drug have shown that it is safe when used in conjunction with widely prescribed statins.
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The new study, published in The New England Journal of Medicine, was the largest study to date to test the efficacy of bempedoic acid, which is yet to be approved in Europe.
The oral medication impedes the body’s ability to create cholesterol, and could be taken in conjunction with patients’ existing statins treatments, as well acting as a treatment for those unable to take statins due to adverse side effects or interactions with other medications.
Low-density lipoprotein (LDL) cholesterol, often dubbed “bad” cholesterol, is responsible for carrying cholesterol to cells. An excess of LDL accumulates on artery walls, restricting blood flow to the heart, brain, and the rest of the body.
This can lead to a number of serious health problems including atherosclerosis, coronary heart disease, heart attack, stroke, and peripheral arterial disease, and can also increase the risk of blood clots throughout the body.
We know that reducing your cholesterol levels is key to cutting the risk of heart attack and stroke, particularly if you already have established heart disease.
Our latest study shows that bempedoic acid could be another addition to the arsenal of cholesterol-lowering treatments available to patients.
What we have is a new class of drug that could be given to patients who are already taking statins and could help them to further reduce their cholesterol levels and thus potentially cut their risk of heart attacks and strokes.”
Professor Kausik Ray, Lead Author
Statins are routinely prescribed to help to lower cholesterol in patients who are at high risk of complications caused by high cholesterol, including those with diabetes, hereditary conditions, and patients who have had a previous heart attack or stroke.
Although bempedoic acid works in a similar way to statins by blocking a cholesterol-producing enzyme ATP-citrate lyase, it boasts some advantages over commonly used statins.
“One of the key advantages of bempedoic acid is supposed to be that it shouldn’t cause the muscle side effects reported by some statins users, as it is taken up by the liver and needs to be converted into its active form via an enzyme only found in the liver,” Ray elucidates.
The study involved 2230 patients, 1488 of whom were given bempedoic acid and 742 a placebo. The patients came from a range of countries, from the UK and Germany to Poland, Canada, and the US.
Along with patients on varying intensities of cholesterol-lowering treatments, patients with familial hypercholesterolemia were also included. Hypercholesterolemia is a hereditary condition that results in increased cholesterol levels and consequent elevated risk of cardiovascular diseases and strokes.
During the 52-week trial, bempedoic acid added to “maximally tolerated statin therapy did not lead to a high incidence of overall adverse events […] and led to significantly lower LDL cholesterol levels.”
After three months, bempedoic acid had reduced LDL cholesterol levels by an average of 18.1% when compared with the placebo group. The intensity of the patients’ existing treatment plans did not affect the efficacy of bempedoic acid.
However, incidence rates of gout within the test group did see a small increase due to slightly higher levels of uric acid in the blood. Incidence of serious health conditions was not reported in either group.
A second study published by The New England Journal of Medicine used data from 654,783 people to investigate the long-term effects of bempedoic acid.
The study tracked genetic markers to determine the potential effects of inhibiting the ATP-citrate lyase enzyme with bempedoic acid. It was then compared with the enzyme that statins usually inhibit, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR).
The study concluded that its results “strongly [imply] that inhibiting ATP-citrate lyase reduces plasma LDL cholesterol levels in the same way that inhibiting HMGCR with a statin reduces LDL cholesterol levels.”
Bempedoic acid was deemed to be potentially equally safe and effective as statins, and that it could also avoid some of the negative muscle-related side effects experienced with statins, as the new medication operates through a different mechanism of action.
“Once converted to the active form [bempedoic acid] cannot leave the liver, so it can’t enter muscles and hence could be of considerable advantage for some,” Ray explains.
Overall, these latest studies show that not only is the treatment generally well-tolerated being comparable with placebo, and potentially safe over longer periods, but that when added to high intensity statin treatment it can help to further reduce LDL cholesterol levels.
The ongoing trial, called ‘CLEAR OUTCOMES’, is specially testing even longer-term safety and whether this approach reduces cardiovascular disease in addition to lowering cholesterol.”
Professor Kausik Ray, Lead Author
Esperion, the US pharmaceutical company that is behind the new drug, is working towards gaining a license to sell the drug in both Europe and the US in 2019. However, there is no certainty that bempedoic acid would be available for patients worldwide within this timeframe.
Mendelian Randomization Study of ACLY and Cardiovascular Disease. NEJM. 14th March 2019.
Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. NEJM. 14th March 2019.