MSD Malaysia recently announced the approval of its new drug to lower cholesterol in Malaysia.

The drug (ezetimibe and atorvastatin) has a dual mechanism of action: it treats the two main sources of cholesterol in the blood by inhibiting the absorption of cholesterol in the digestive tract (through ezetimibe) and the production of cholesterol in the liver (atorvastatin).

The once-daily combination tablet is indicated to reduce the risk of cardiovascular events in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS), either previously treated with statins or not.

The drug is indicated as an adjunctive therapy to diet for use in adults with primary (heterozygous familial and non-familial) hypercholesterolaemia or mixed hyperlipidaemia in patients not appropriately controlled with a statin alone or already treated with a statin and ezetimibe.

It is also indicated as adjunctive therapy to diet for use in adults with homozygous familial hypercholesterolaemia.

Understanding cholesterol

Cholesterol is a waxy substance that is produced in the liver and can also be found in foods from animal sources, such as meat, poultry and full-fat dairy products.

More cholesterol is produced by the liver when a person eats a diet high in saturated and trans fats.

The human body needs cholesterol to build cell membranes, make certain hormones and produce compounds that aid in fat digestion.

However, excess cholesterol can form plaque between layers of artery walls, making it harder for the heart to circulate blood. Plaque can break open and cause blood clots. If a clot blocks an artery that feeds the brain, it causes a stroke. If it blocks an artery that feeds the heart, it causes a heart attack.

Cholesterol, cardiovascular disease, heart disease, stroke, heart attack, Star2.com

Dr Robaayah shows a normal artery (left) and one clogged with plaque (right). — MSD

“Hypercholesterolaemia is asymptomatic whereby patients will not experience any symptoms. Most patients are not aware that their cholesterol level is high and the only way to detect this is through routine screening.

“Thus, if left unchecked, hypercholesterolaemia may lead to various cardiovascular (CVS) diseases such as heart attacks and strokes. Without treatment, a CVS attack can lead to serious health problems or even death,” explained consultant cardiologist Tan Sri Dr Robaayah Zambahari at the launch of the drug.

According to the National Health & Morbidity Survey 2015, the overall prevalence of hypercholesterolaemia (known and undiagnosed) among adults of 18 years and above in Malaysia was 47.7%.

There was a general increasing trend with age, from 22.0% in the 18-19 years age group, reaching a peak of 68.8% among the 55-59 years age group.

Along with a healthy diet, statins are the first-line lipid-lowering therapy to reduce high LDL (LDL-C; bad cholesterol) cholesterol levels in patients when drug therapy is appropriate.

More than half of the participants, particularly in patients at highest CVS risk, including those with CHD or diabetes in the REALITY Asia study did not accomplish recommended levels of LDL-C.

Among the small group of patients whose statin dose was up-titrated, 56% of them did not achieve their cholesterol goal of less than 100mg/dl LDL-C after 12 months of therapy.

When the target of less than 70mg/dl was considered, approximately 72% of patients with CHD or diabetes failed to achieve this goal after their statin doses were up-titrated.

“Recent guidelines state that there is evidence suggesting that lower LDL-C level is associated with fewer CV events; the greater the LDL-C reduction, the greater the CVS risk reduction.

“These benefits related to LDL-C reduction are not specific to statin therapy. Therefore, it seems appropriate to reduce LDL-C as low as possible, at least in patients at very high CVS risk,” observed consultant cardiologist Dr David Quek during the launch.

Effective therapy

The new drug has been shown in multiple studies to effectively lower LDL-C.

In a six-week, multicentre, double-blind, randomised, parallel-group study, 196 patients with hypercholesterolaemia who were treated for six weeks were shown to have significantly greater LDL-C reduction, compared with doubling the dose of atorvastatin.

In the IMPROVE-IT study with 18,144 ACS patients, the treatment with ezetimibe/simvastatin provided incremental benefit in reducing the primary composite endpoints of cardiovascular death, non-fatal myocardial infarction, documented unstable angina that required hospitalisation, any coronary revascularisation procedure occurring at least 30 days after randomised treatment assignment and non-fatal stroke compared with simvastatin alone (relative risk reduction of 6.4%).

This incremental benefit is expected to be similar with the new drug, which is the coadministration of ezetimibe and atorvastatin.

“The launch of this new therapy enables healthcare professionals to think beyond statin monotherapy when treating patients struggling to achieve their cholesterol level goals.

“The combination of ezetimibe and atorvastatin represents a new breakthrough, which MSD hopes will address the critical unmet needs of patients in Malaysia,” said Chris Tan, Managing Director and Zone Leader for MSD Malaysia, Singapore and Brunei after the official launch.

The drug has been evaluated for safety in more than 2,400 patients in seven clinical trials. It was generally well tolerated, with common side effects including diarrhoea and myalgia.