Statin+Ezetimibe reduces the burden of high doses Statin

Rx of Statin+Ezetimibe, quarterly Rx exceeded 100 billion

Consideration of combination drugs first due to concerns about diabetes, Metabolic benefits

Kim Dae-jung, a 50-year-old professor of endocrinology at Ajou University Hospital

The 'Statin + Ezetimibe' combination drug is shaking the market for hyperlipidemia treatment.

 

In 2015, the 'IMPROVE-IT' study, which proved the low-density lipoprotein cholesterol (LDL-C) lowering effect of the combination therapy of Ezetimibe(non-statin) and Statins, targets a niche market that is concerned about side effects of high-dose Statins.

 

Statin+Ezetimibe combination domestic market, led by 'Rosuvastatin + Ezetimibe', is growing day by day.

 

This market, which was ₩23.8 billion in the first quarter of 2016, has expanded to ₩111.4 billion in the second quarter of 2020.

 

The combination of Statin + Ezetimibe is also becoming a trend in the frontline medical field.

 

Kim Dae-jung, a 50-year-old professor of endocrinology at Ajou University Hospital, said in a meeting with Dailypharm that "the trend is to use a combination of 'Statin + Ezetimibe' for preventive purposes not only for high risk of cardiovascular disease, but also for patients who need to lower LDL-C." "The combination of Statins and Ezetimibe reduces concerns about diabetes and provides metabolic benefits, which is a factor in considering this combination from the beginning." Prof.

 

Kim also participated in a retrospective domestic cohort study of Koreans who concluded that taking a high dose of Statin for a long time increases the risk of diabetes.

 

This study, published in the journal Cardiovascular Diabetology, an SCI-level international academic journal, was conducted in 13,698 adults aged 40 to 74 years old who were diagnosed with dyslipidemia without a history of diabetes or atherosclerotic cardiovascular disease(5,273 people in the Statin group & 5,273 people in the non-statin group), and the cumulative incidence of type II diabetes according to the annual accumulated daily dose of Statin was evaluated by follow-up method.

 

As a result of the analysis, type II diabetes occurred in a total of 3,034 patients during the average observation period of 7.1 years, of which more than half of 1,871 patients (61.7%) occurred in the Statin group.

 

As the duration of Statin administration was longer than 5 years, the risk of diabetes was significantly increased compared to that of the non-administered group, and the risk of diabetes incidence increased from 1.31 times to a maximum of 2.83 times compared to the non-administered group in proportion to the total cumulative dose of Statin consumed annually.

 

▶What is the implication of a recent study on the link between high statin doses and diabetes incidence?

 

Long-term high doses of Statins increase the risk of diabetes.

 

Conversely, Statins should be used as low as possible.

 

However, in order to be effective enough to prevent cardiovascular disease, certain amount of Statin should be used.

 

As the target LDL-C level is reached, the alternative to use less Statin is Ezetimibe combination, which is non-statin formulation In fact, there are many cases of prescribing a combination of Ezetimibe rather than a single statin drug to patients who need to use high doses of statins.

 

Prescribing data proves this, and it seems that Ezetimibe combination is also preferred for the purpose of preventing cardiovascular disease.

 

Even when I need to use a high dose of Statins, I often use ezetimibe complex from the beginning.

 

▶Are you concerned about the side effects of high doses of statins?

 

According to the actual clinical data, the risk of developing muscle side effects such as rhabdomyolysis, which is commonly known, is rare, so it is not enough to worry.

 

The same goes for concerns about side effects related to the liver.

 

However, having these side effects (even if the side effects are rare) puts great stress on the doctor.

 

The idea that I want to avoid it as much as possible makes me choose the alternative Ezetimibe combination.

 

Concerns are higher about the occurrence of diabetes, which is cited as another side effect.

 

In particular, high-risk groups for cardiovascular disease, who are prescribed high doses of Statin, are often highly likely to develop diabetes.

 

Patients at high risk of diabetes may consider Ezetimibe combination from the start, as mentioned earlier.

 

▶Are there any other benefits of Statin+Ezetimibe?

 

While Statins inhibit cholesterol synthesis in the liver, Ezetimibe's mechanism inhibits cholesterol absorption in the small intestine.

 

When cholesterol is absorbed, it forms Chylomicron like triglycerides and moves into the blood, blocking the process.

 

In other words, using Ezetimibe can reduce the absorption of not only cholesterol but also triglycerides.

 

▶In the area of hyperlipidemia, which used to be Statin only, combination drugs of other classes, such as diabetes and hypertension, seem to be increasingly taking up a larger proportion.

 

This is because of the advantages of combination therapy.

 

As with diabetes, rather than raising a certain drug to the highest dose, using one drug at an appropriate dose while using a little bit of another drug seems to be able to produce the desired effect while minimizing side effects.

 

It is clear that the combination system is far more beneficial than using each single drug.

 

As it is a chronic disease that must be taken for a lifetime, the number should be reduced and the dosage method should be simplified.

 

This can increase patient compliance.

 

▶Research is ongoing to establish the basis for the combination therapy of 'Statin + Ezetimibe'.

 

Recently, a study is underway in Korea to directly compare high doses of Statin and combination therapy in more than 3,000 domestic patients.

 

You can't predict the outcome, but what if you predict the direction?

 

Since the cardiovascular prophylactic effect is formulated according to the target LDL-C level, if the combination therapy with high-dose Statin and Ezetimibe similarly reduces the LDL-C level or reaches the target level, it will be considered similar in terms of efficacy.

 

Furthermore, what is expected of Ezetimibe combination therapy is to reduce diabetes incidence or to show better safety data.

 

It seems that we will have to wait for the results of the study to see if the predictions will come out as real data.