Dyslipidemia is regarded as a significant cause of cardiovascular disease here and abroad, and therapeutic approaches are becoming increasingly important. In particular, statistics show that two out of five adults in Korea have dyslipidemia, and one out of four have hypercholesterolemia.

Untreated dyslipidemia can cause cholesterol to build up in the walls of blood vessels, leading to atherosclerosis. This significantly increases the risk of cardiovascular events, including angina, myocardial infarction, and stroke. Lowering LDL cholesterol levels is, therefore, considered to be an important factor in managing dyslipidemia to prevent cardiovascular disease and reduce mortality.

Statin drugs have a long history of use as first-line agents of choice in treating dyslipidemia and have proven effective in preventing cardiovascular diseases.

In particular, they are effective in preventing recurrent cardiovascular events and death in patients who have already had one. The European Society of Cardiology (ESC) guidelines and other recent studies emphasize that lowering LDL cholesterol as much as possible reduces the risk of cardiovascular events. In March, the ESC recommended statins as the first-line drug for treating dyslipidemia in all patients, including older adults, reiterating the importance of statins.

Statins are also actively used in Korea.

Crestor (rosuvastatin), which recently celebrated its 20th anniversary of launch in Korea, is often referred to as a “super statin” because it has indications for controlling hypercholesterolemia, delaying the progression of atherosclerosis, and reducing the risk of cardiovascular disease.

Korea Biomedical Review spoke with Dr. Oh Ju-hyeon, a professor of cardiology at Samsung Changwon Hospital, Sungkyunkwan University, about the current status of dyslipidemia in Korea, the benefits of statin monotherapy as confirmed by clinical trials, and the clinical benefits of high-intensity statins.

Question: Please explain the prevalence of dyslipidemia in Korea and its social impact.

Answer: According to the National Health and Nutrition Survey, the number of patients with dyslipidemia has increased dramatically from 8.8 percent of the population in 2007 to 22.0 percent in 2022. While hypertension is relatively well diagnosed and treated, dyslipidemia records low treatment rates, with four out of 10 patients unaware of their condition. That poses a serious threat to public health. Studies show that treating dyslipidemia reduces the risk of cardiovascular events from 36.9 to 20.9 per 1,000 people, so aggressive treatment and management is essential.

Q: The prevalence of dyslipidemia is high, but the treatment rate is low in Korea compared to other chronic diseases. Why?

A: Let me compare it to other chronic diseases, such as hypertension, where blood pressure is easily measured with a simple test, and the risks are well understood. Blood pressure can be easily measured at most pharmacies and neighborhood clinics, and hypertension is highly publicized because it is associated with symptoms including headaches and serious diseases such as stroke. Thanks to this awareness, the incidence of stroke, especially cerebral infarction, has decreased significantly in Korea. On the other hand, dyslipidemia is difficult to detect without a blood test. Regular screening and management are essential. Still, many people do not realize the severity of the disease because they do not have any symptoms.

Q: Tell us about the latest treatment strategies for dyslipidemia.

A: The ultimate goal of dyslipidemia treatment is to lower LDL (low-density lipoprotein) cholesterol levels. National and international treatment guidelines recommend statins as first-line therapy, with LDL cholesterol as the primary target. If LDL cholesterol levels are not sufficiently lowered after statins, additional fibrates or omega-3 fatty acids may be used for patients with low HDL (high-density lipoprotein) cholesterol, diet and exercise are recommended over medication.

The so-called “Low is Better, Early is Better” strategy for treating dyslipidemia proposed in the 2018 U.S. guidelines and 2019 European guidelines is based on the concept that lowering LDL cholesterol levels as quickly and aggressively as possible is effective in preventing cardiovascular events. The ESC recommends lowering LDL cholesterol levels to less than 70 mg/mL for patients at high risk and less than 55 mg/mL for those at very high risk.

The 2022 national guidelines follow the ESC's recommendation and suggest lowering LDL cholesterol levels to less than 70 mg/mL for high-risk patients and less than 55 mg/mL for high-risk patients. They also aim to reduce at least 50 percent from baseline, which is recommended to be customized based on the patient's condition.

For example, patients who have had an acute myocardial infarction, diabetes with cardiovascular disease, or a family history of cardiovascular disease are classified as ultra-high risk and should aim for lower LDL cholesterol levels. In contrast, patients without cardiovascular disease are assessed for risk based on the five major risk factors, and LDL cholesterol targets are set.

In addition to LDL cholesterol, the five major risk factors for cardiovascular disease are:

● Age (45 years or older for men and 55 years or older for women)

● Family history of premature coronary artery disease (onset before age 55 for men and before age 65 for women)

● High blood pressure

● Smoking status

● Low HDL cholesterol (less than 40 mg/dL)

If you have one or fewer risk factors, it is recommended that you lower your LDL cholesterol to less than 160 mg/dL. If you have two or more, you are considered at moderate risk and should lower it to less than 130 mg/dL.

Q: Explain how to use statins effectively and what to consider during treatment.

A: When prescribing a statin, we first assess the patient's risk factors and establish a target LDL cholesterol level based on whether the patient already has cardiovascular disease or is taking the statin for risk factor control. It is common to use low- or moderate-intensity statin therapy, with stronger statin prescriptions for high-risk patients who already have cardiovascular disease.

Q: Which is better, increasing statins slowly to a targeted dose or combining statins with ezetimibe?

A: Treatment should be based on guideline recommendations. At the end of the day, however, it's important to personalize treatment for each patient. Statin and ezetimibe combinations are effective in lowering LDL cholesterol. It is also possible to use these combinations selectively in the clinic for patients who need them. However, clinical data on combination therapy is still lacking. This is not to say that combinations are bad, but it is recommended that statins be used according to guidelines first and then a combination if needed.

Q: What are the critical factors you consider when prescribing among the various statin drugs?

A: In the medical field, we often prescribe statins in high doses because we see many high-risk patients or patients who already have cardiovascular disease. As demonstrated in several studies, Crestor is considered one of the most potent statins available, so it tends to be favored by these patients.

Q: Please tell us a typical clinical case referred to in prescribing Crestor and the results.

A: Crestor is known to be superior to other statin drugs in providing potent LDL cholesterol and triglyceride lowering and effective HDL cholesterol management. The pivotal STELLAR study showed that 20 mg of Crestor was more effective at lowering LDL cholesterol than all doses of atorvastatin, simvastatin, and pravastatin.

Crestor was also better at managing HDL cholesterol, increasing it from 7.7 percent to 9.6 percent compared to other statins (from 2.1 percent to 6.8 percent). In reducing triglycerides, Crestor reduced triglycerides by 19.8 percent to 26.1 percent, which was stronger than simvastatin (11.9 percent-18.2 percent) and pravastatin (7.7 percent- 13.2 percent).

Q: How should patients, including their tolerability, be managed when prescribing Crestor?

A: Crestor is characterized by fewer drug interactions with other medications. Most drugs currently used in clinical practice are metabolized by CYP450 3A4, whereas Crestor is metabolized by CYP450 2C9, which reduces the risk of drug interactions. Because it has fewer drug interactions with other medications commonly used in the chronically ill, such as calcium blockers and athlete's foot medications, the risk of adverse effects is low, and liver enzyme elevations and muscle pain have been reported less frequently than with other statins.

Q: Crestor is the only statin indicated for delaying the progression of atherosclerosis in patients with hypercholesterolemia. What is its clinical significance?

A: Crestor is the only statin indicated for delaying the progression of atherosclerosis. In the 2006 ASTEROID study, 40 mg of Crestor was prescribed to patients with narrowed coronary arteries and demonstrated a significant reduction in atherosclerosis, making it the first statin to demonstrate a slowing of atherosclerosis progression.

In addition, the 2007 METEOR study measured carotid artery intima-media in hypercholesterolemic patients at low risk for coronary heart disease and found that Crestor 40 mg was the only statin to inhibit progression compared to placebo. Based on these findings, Crestor gained an additional indication for delaying the progression of atherosclerosis. The COSMOS study in Japan in 2009 and the ARTMAP study in Korea in 2012 confirmed Crestor's atherosclerosis-reducing effects.

The core problem of dyslipidemia is ultimately caused by atherosclerosis (fatty deposits in the arteries), and by reducing this atherosclerosis, Crestor may play an important role in addressing the root cause of the disease.

Q: We understand that some Koreans have concerns about its effectiveness and tolerability due to genetic differences from Westerners. Are these concerns valid?

A: The JUPITER study showed that Crestor is effective in primary prevention of cardiovascular disease. This study found that 20 mg of Crestor reduced the risk of cardiovascular events in patients with LDL cholesterol levels as low as 130 mg/dL but high high-sensitivity C-reactive protein (hsCRP) levels as high as 2.0 mg/L. However, about 97 percent of the patients in the JUPITER trial were white, black, or Hispanic, and there was a lack of certainty about the effect on Asians.

However, the publication of the HOPE-3 study addressed these concerns. The HOPE-3 study included 49 percent of Asians, including Koreans. The results showed that Crestor significantly reduced the risk of cardiovascular events in a wide range of ethnicities, including Asians, demonstrating that it is effective for primary prevention regardless of ethnicity. Therefore, there are no major concerns about the effectiveness and tolerability of Crestor in Koreans.

Q: Various studies have shown statins are good drugs. Yet, know that patients have concerns about side effects, such as muscle pain and diabetes. What are your criteria for prescribing statins in this situation, and how do you communicate with patients?

A: When prescribing statins, physicians must carefully review side effects. Patients are often concerned about side effects, such as muscle pain and diabetes, and physicians hear these concerns repeatedly, which makes them cautious.

However, several studies and treatment guidelines recommend using statins at the maximum dose as the first line of therapy, with the addition of an omega-3 fatty acid, fibrate drug combination, or PCSK9 inhibitor if target LDL cholesterol levels are not achieved.

Statins have been shown to be effective, especially in older adults. However, age is a risk factor for statin intolerance, so starting with a lower dose is recommended. In addition, older adults are often taking many concomitant medications, so dosing should be carefully adjusted to account for drug interactions.

Clearly explaining the reasons for statin use is important regarding communication with patients. However, do not over-explain the side effects at the outset to avoid the “nocebo effect,” which increases the likelihood that patients feel side effects. If patients ask about side effects, explain that they are likely to occur but emphasize that they should not be discontinued arbitrarily because of them. Also, prioritize the benefits of statins in reducing the risk of cardiovascular events while plausibly explaining the potential for diabetes.

Q: What do you see as areas for improvement in dyslipidemia care?

A: Although the prevalence of dyslipidemia continues to rise, four out of 10 people are not even aware that they have it. Increasing awareness is the first goal, as 87 percent of dyslipidemia is controllable with treatment. Increased awareness will naturally lead to treatment. The national health examination for dyslipidemia screening is only done once every four years. However, a biannual screening could increase awareness. If treatment begins after the disease has worsened, the societal costs could be even greater and strain health insurance finances.

Q: Finally, what would you like to say to healthcare providers who prescribe statins or to patients who take them?

A: Guidelines are well established, and it is important to assess a patient's risk factors carefully and select and manage statins to achieve target LDL cholesterol levels. Following up and ensuring you're reaching your goal rather than just taking the medication is essential.

Besides, many patients are concerned about the side effects of statins, but side effects are not unique to statins. Drug interactions can occur, especially in Korea, where older adults often take multiple medications at the same time. Rather than simply blaming statins and giving up statins or adjusting the dose, it may be more appropriate to look at other medications and reduce them. While other medications are aimed at improving symptoms, statins are life-saving and should not be given up easily.