Cholesterol-lowering drugs

Overview of Treatment

Cholesterol-lowering medications are a class of drugs used to regulate lipid levels in the blood, primarily targeting low-density lipoprotein cholesterol (LDL-C, commonly known as "bad cholesterol") and triglycerides to reduce the risk of cardiovascular disease. These drugs work by inhibiting cholesterol synthesis, promoting metabolism, or blocking absorption, helping patients keep blood lipids within safe ranges. They are commonly used in clinical settings for hyperlipidemia, arteriosclerosis, and cardiovascular disease prevention.

The treatment goals typically include reducing LDL-C levels to personalized target values, combined with dietary and exercise interventions to enhance efficacy. Physicians tailor individualized treatment plans based on patient age, medical history, and severity of complications.

Types and Mechanisms of Treatment

Currently, there are five main categories:

  • Statins: Inhibit hepatic HMG-CoA reductase, blocking cholesterol synthesis.
  • PCSK9 Inhibitors: Enhance hepatic clearance of LDL receptors, accelerating cholesterol metabolism.
  • Bile Acid Sequestrants: Bind intestinal bile acids, promoting their excretion to lower cholesterol.
  • Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: Use monoclonal antibodies to reduce LDL-C levels.
  • Cholesterol Absorption Inhibitors: Block intestinal absorption of dietary cholesterol.

Different mechanisms can be combined, such as statins with PCSK9 inhibitors, to significantly enhance lipid-lowering effects. Physicians adjust combination strategies based on patient response and tolerability.

Indications

Mainly used for primary hypercholesterolemia, familial hypercholesterolemia, or patients with angina, myocardial infarction, and other cardiovascular diseases. When lifestyle interventions (such as diet control and exercise) fail to meet targets, medication becomes a necessary option.

In specific cases, also used for diabetic patients with hyperlipidemia, kidney disease, or familial mixed hyperlipidemia. Doctors decide whether to initiate drug therapy based on the patient’s 10-year cardiovascular risk assessment.

Usage and Dosage

Most drugs are oral tablets taken once daily, some with dinner (e.g., bile acid sequestrants). PCSK9 inhibitors are subcutaneous injections administered every 2 weeks or monthly. Initial doses are usually lower, with gradual adjustments based on lipid profile results.

During treatment, regular monitoring of liver function, muscle enzyme levels, and blood lipid concentrations is required. For example, statins should be evaluated after 6 weeks; if LDL-C targets are not met, dosage may be increased or additional medications added.

Benefits and Advantages

Clinical evidence shows that statins can reduce the risk of heart attacks by up to 30-40%, and PCSK9 inhibitors can further lower LDL-C by an additional 75%. Most drugs offer the following advantages:

  • Effectively slow the progression of atherosclerosis
  • Can synergize with other cardiovascular drugs (such as antihypertensives)
  • Provide personalized treatment options, such as non-hepatically metabolized drugs for those with liver dysfunction

Risks and Side Effects

Common side effects include muscle soreness, elevated liver enzymes, and gastrointestinal discomfort. Statins may cause rhabdomyolysis (rare but serious), requiring close monitoring of creatine phosphokinase (CPK) levels. PCSK9 inhibitors may cause injection site redness or swelling, and high-dose niacin may lead to blood sugar abnormalities.

Serious Precautions: Avoid concomitant use with certain drugs (such as some antifungals) to reduce muscle toxicity risk. Pregnant or breastfeeding women are generally contraindicated for these medications.

Precautions and Contraindications

Contraindications include active liver disease, severe renal failure, and hypersensitivity to drug components. During treatment, excessive alcohol intake should be avoided, and liver function tests performed regularly. Some drugs may affect vitamin D or K metabolism, requiring monitoring of related indicators.

If patients experience unexplained muscle pain, dark urine, or severe diarrhea, they should stop medication immediately and seek medical attention. All concomitant medications, especially anticoagulants or immunosuppressants, should be disclosed to the physician before treatment.

Interactions with Other Treatments

Combining with HDL-raising agents like fibrates may increase muscle toxicity risk; concomitant use with antifungal drugs like ketoconazole can elevate statin blood levels. Certain antibiotics (e.g., tetracyclines) may reduce efficacy, requiring timing adjustments. Traditional Chinese medicines such as red yeast rice contain natural statins, which may enhance side effects when used with Western medications. Patients should inform their physicians of all supplements used before treatment.

Therapeutic Efficacy and Evidence

Large studies like IMPROVE-IT show that combining statins with ezetimibe can further reduce cardiovascular event risk by 6%. The ODYSSEY trial confirmed that PCSK9 inhibitors can lower LDL-C by 50-70%. Combining medication with antihypertensive and antidiabetic drugs can reduce 10-year cardiovascular risk by 40-60%.

Long-term follow-up indicates that regular use can significantly delay the progression of arterial plaques. However, drug effects may vary due to genetic factors (such as SLCO1B1 polymorphisms).

Alternatives

Non-pharmacological treatments include the Mediterranean diet, 150 minutes of aerobic exercise weekly, and weight management. Alternative options include:

  • Fibrates (for high triglycerides)
  • Niacin (used cautiously due to potential blood sugar effects)
  • Emerging ANGPTL3 inhibitors (for specific genetic types)

In cases of drug intolerance, lipid absorption inhibitors (such as ezetimibe) or LDL apheresis can be considered as last-resort treatments for severe cases.

 

Frequently Asked Questions

When taking lipid-lowering medications, is it necessary to follow specific dietary restrictions?

Yes. Patients are advised to follow a low-fat, low-cholesterol diet, and increase dietary fiber intake when taking lipid-lowering drugs (such as statins). Avoid excessive intake of greasy, processed foods, and alcohol to enhance drug efficacy. Some medications may interact with certain foods or supplements, so follow your doctor’s dietary instructions.

If muscle pain or weakness occurs, how should it be managed?

Muscle discomfort is a potential side effect of lipid-lowering drugs. Patients should report symptoms to their physician immediately. The doctor may adjust the dosage or switch medications. Avoid strenuous exercise and regularly check CPK levels. Do not stop medication on your own to prevent rebound in blood lipids.

Is exercise or other lifestyle changes necessary to improve treatment outcomes?

Yes. Regular aerobic exercise (such as brisk walking or swimming) combined with dietary control can enhance the LDL-lowering effect of medications. It is recommended to perform at least 150 minutes of moderate-intensity exercise weekly and reduce sedentary behavior. Lifestyle modifications complement medication therapy for effective blood lipid control.

How often should blood lipid and liver/kidney function tests be performed during treatment?

Initially, blood tests are usually scheduled every 3 to 6 months, with liver function assessed after 4 to 12 weeks of therapy. For statins, regular monitoring of liver enzymes ALT/AST is necessary. The frequency can be adjusted based on individual health status; more frequent monitoring may be needed for high-risk or elderly patients.

If a patient has diabetes or hypertension, how will the treatment plan be adjusted?

Patients with metabolic syndrome may require drugs with multiple benefits (such as PCSK9 inhibitors or ezetimibe), combined with blood sugar and blood pressure control strategies. Treatment goals are more stringent, with LDL-C reductions exceeding 50%. Regular assessment of comorbidity risks and medication adjustments are essential to avoid interactions.