Why Ezetimibe combination drug for dyslipidemia?

Interview on Executive Officer Chae In-ho of Korean Society of Interventional Cardiology

Added on from the get-go for patients with high risk

Highly recommended for drug compliance and cost purposes

Professor Chae In-ho

For some diseases, combination drugs are vastly preferred than the other.

 

Dipeptidyl peptidase-4 inhibitor plus metformin combination for patients with diabetes, and angiotensin II receptor blocker (ARB) plus calcium channel blocker (CCB) plus alpha combination for patients with hypertension haven taken over significant part of respective overall prescription volumes.

 

And combination drug is also on the rise for dyslipidemia treatment sector for last few years.

 

The combination of statin and ezetimibe is the case.

 

Despite many of specialists’ skepticism on ezetimibe, the drug has proven its catchphrase ‘the lower the LDL-C the better the benefit for cardiovascular system’ in the IMPROVE-IT trial that unveiled in 2015.

 

Since then, the combination drug has gained popularity fast.

 

Basically, ezetimibe-based combination drugs with either rosuvastatin or atorvastatin have shifted the market previously dominated by statin.

 

Daily Pharm interviewed Executive Officer Chae In-ho of Korean Society of Interventional Cardiology (KSIC) (Director of Cardiology Center at Seoul National University Bundang Hospital) about the benefits of combination drugs and ezetimibe.

 

-Do you prefer to prescribe ezetimibe-based combination drug?

 

It would be safe to say the combination drugs have taken deep root as effective dyslipidemia treatment.

 

For a long while, hyperlipidemia treatment was solely relying on statin and used high dosage.

 

But nowadays, non-statin combination therapies previously marginalized have stolen the limelight again.

 

Compared to same dose of statin, ezetimibe combination therapy has similar incidents of side effects but shows even more benefit in reducing LDL-C.

 

When higher dose of statin is used, a patient’s LCL-C level at 100 mg/ dL would fall to 90 mg/ DL, but using ezetimibe combination the numbers fall even lower to 70 mg/ dL.

 

-Is there any other reason why you would prefer the combination drug over the single drug?

 

First of all, it would the convenience for sure.

 

Administration convenience is far superior and drug compliance is also very high.

 

Patients tend to ask a lot more questions than before when they get additional number of pills and they come prepared with basic online research.

 

The patients are happy to hear my explanation about the combination drug not increasing the number of pills but resulting in better effect.

 

Besides, the price of combination drugs in Korea are inexpensive than in other countries.

 

Patients with chronic disease get sensitive about the cost, so the health insurance system is a plus factor for preferring a combination drug.

 

-For the combination drug, there is a choice between rosuvastatin and atorvastatin.

 

Is there a deciding factor when prescribing the combination drug?

 

I don’t personally see a big difference.

 

But I prefer prescribing rosuvastatin plus ezetimibe for a stronger effect.

 

Using 20 mg of rosuvastatin and 40 mg of atorvastatin show similar level of effect, but I feel rosuvastatin lowers LDL-C better in combination.

 

Of course, pharmaceutical companies could say otherwise.

 

Anyway, now atorvastatin has more options with 80 mg dose added to combination option.

 

-Is it possible to use ezetimibe combination on dyslipidemia patient as first-line therapy?

 

Yes.

 

For patients with high risk in acute coronary syndrome (ACS), myocardial infarction (MI) and unstable angina, a combination drug is used for an initial treatment.

 

But for a relatively young patient with risk of arteriosclerosis, high-dose combination drug is used.

 

As diabetic patient tend to have accelerated absorption of cholesterol, ezetimibe could demonstrate more dramatic effect.

 

Because statin causes diabetes more frequently than ezetimibe, it would be more effective to specific patient group with high blood sugar level.

 

Diabetes is treated not only with medication, but also with lifestyle.

 

Cholesterol, relatively more controllable with medicine, should be managed with pharmaceutical push as much as it can.

 

-Regardless, the 2018 dyslipidemia treatment guideline recommended ezetimibe therapy as a second-line therapy.

 

And when the U.S.

 

and Europe recommended LDL-C level of the mentioned groups with very high risk to be lowered to 55 mg/ dL and 40 mg/ dL, respectively, Korea recommended the level to be lowered to 70 mg/ dL.

 

Basically, I agree with the phrase, “The lower the better.” But a guideline is merely a guideline in the end.

 

Using the combination drug for first-line treatment means it’s targeting even more effective LDL-C reduction benefit, which coincides with the mechanism of ‘the lower the better.’ But if you’re asking whether to target 70 mg/ dL or 55 mg/ dL, it would be different case by case.

 

I would be skeptical to prescribe higher dose or stronger drug to lower LDL-C of 80 mg/ dL in a patient with high risk, but who works out regularly and manages body weight.

 

Probably 70 percent of clinicians in Korea and 25 percent in the U.S.

 

would consider the guideline’s recommendation.

 

Ultimately, it is a matter for a physician to judge and decide from their experience and expertise.

 

Ezetimibe combination drug has diversified the choices, and it would be more frequently used as it accumulates prescription history.