Drug selection for lipid management and prevention of coronary heart disease: From the scientific application of statins to the identification of inducing factors

Treatment Focus: Beyond Lipid-Lowering – Eliminating Atherosclerotic Plaques. Prevention and Treatment Focus: ● For patients with dyslipidemia, comprehensive screening for other related cardiovascular and cerebrovascular disease risk factors is necessary, including at least: obesity, blood pressure, blood sugar, coronary heart disease, and ischemic cerebrovascular disease. ● Patients with existing cardiovascular and cerebrovascular disease risk factors or hyperlipidemia should undergo regular (every 3-6 months) lipid testing (TC, LDL-C, HDL-C, TG, etc.). ● For triglyceride levels >500 mg/dL (5.6 mmol/L), niacin or fibrates should be used first to control triglycerides and prevent acute pancreatitis; otherwise, for patients with cardiovascular and cerebrovascular diseases and related conditions, the primary goal is to lower LDL (or achieve target levels) with statins. ● During treatment, monitor for adverse drug reactions, and check liver function and muscle enzymes before and after treatment, especially when statins are used in combination with other lipid-lowering drugs to avoid the side effect of myofibrosis.

(I) Non-pharmacological treatment. The treatment plan is determined based on the patient's presence of cardiovascular and cerebrovascular diseases and their risk factors, as well as their blood lipid levels. Lifestyle modifications are the first step in treating dyslipidemia and must be implemented throughout the entire treatment process.

(II) Drug Therapy. 1. Drug Selection. The choice of drug should be determined based on the patient's blood lipid level and the type of dyslipidemia. (1) Simple TC elevation or mixed type with TC and LDL elevation as the main factors: statin drugs are selected for treatment, and combination drugs can be used if necessary; (2) Simple TG elevation or mixed type with TG elevation as the main factor: fibrate drugs are selected for treatment, and combination drugs can be used if necessary; (3) Low HDL-C as the treatment target: niacin or fibrates; (4) The status of statin drugs: important clinical significance. All cardiovascular and cerebrovascular disease patients whose blood lipids have not reached the treatment target level should receive long-term statin lipid-lowering drug treatment, as long as there are no contraindications to the use of statins, and efforts should be made to control blood lipids at the ideal level according to their risk stratification. Other lipid-lowering drugs can be added if necessary. If the patient has contraindications to statin treatment, other lipid-lowering drugs such as fibrates, resins, niacin, etc. can be considered. The role of statins in the prevention and treatment of cardiovascular and cerebrovascular diseases has been gradually increasing in recent years. This is because statins can not only regulate lipids, but also repair damaged vascular endothelium, inhibit the inflammatory response of atherosclerotic plaques, form a protective layer, stabilize or even reverse them, reverse thickened arterial intima thus improving arterial stenosis, and also have anti-platelet aggregation effects. Numerous studies have confirmed that statins can indeed reduce cardiovascular and cerebrovascular events, and the longer the course of treatment, the better. It is generally believed that long-term use can reduce the incidence of cardiovascular and cerebrovascular events by 20%-30%, and large-scale clinical studies have shown that after more than 6 years of use, low doses can reduce the incidence by 30%, and medium and high doses can reduce the incidence of cardiovascular and cerebrovascular events by 50%.

(5) The role of statins: issues to be aware of. Patients with cardiovascular and cerebrovascular diseases need to take statins for a long time, so attention should be paid to their toxic side effects, compatibility issues and contraindications.

●Adverse reactions to statins are commonly seen in: ①Elderly individuals, especially those over 80 years of age, those with a small build, and those who abuse alcohol; ②Multi-system diseases: hepatic or renal insufficiency, diabetic nephropathy; ③Persons taking multiple medications, post-transplant patients, HIV patients, those with neuromuscular diseases, arrhythmias, hypertension, post-PCI, severe infections, shock, or during surgery; ④Most commonly seen in:concomitant use with fibrates (especially gemfibrozil), niacin, erythromycin, cyclosporine, pyrrole antifungals, verapamil, amiodarone, alcoholism, and excessive dosage.

●Important adverse reactions of statins include: Elevated liver transaminases: The vast majority of these are isolated and asymptomatic elevations in liver transaminases, with no clear relationship to liver failure: ① The vast majority of elevations are less than 3 times the normal value, usually mild and transient, without clinical symptoms, and can recover spontaneously without the need to interrupt treatment. Even without dose adjustment, 70% will decrease spontaneously. ② Even if the elevation is more than 3 times the normal value, it usually returns to pre-treatment levels within about one month after dose reduction or discontinuation. Re-reduction of the dose or switching medication can then be attempted again. ③The significance of elevated muscle enzymes and the prevention of myopathy.

●The incidence of muscle discomfort varies among different statins, with a very low incidence in severe cases (<10 cases per million prescriptions); except for patients susceptible to myopathy, it is not always necessary to measure CK (creatine kinase).

● For patients who can tolerate myalgia and weakness, if CK levels are less than 5 times the normal value (mild elevation), the original dose can be maintained or the dose reduced; if CK levels are greater than 5 times the normal value (moderate elevation), medication should be discontinued.

● For patients with severe muscle pain or weakness, statins should be discontinued regardless of CK levels. Wait until symptoms disappear before trying a low dose, or switch to a different statin.

●Muscle damage most commonly occurs in patients with multiple co-existing conditions and/or those using multiple medications. The incidence of myositis increases when using high-dose statins or in combination with other drugs, including fibrates, niacin, cyclosporine, macrolide antibiotics, and certain antifungal drugs;

● Rhabdomyolysis refers to muscle symptoms accompanied by a significant increase in CK levels exceeding 10 times the upper limit of normal and elevated creatinine, often accompanied by brown urine and myoglobinuria.

Introduction to Coronary Artery Disease (CAD). CAD refers to heart disease caused by myocardial ischemia, hypoxia, or necrosis due to hardening, narrowing, blockage, or spasm of the coronary arteries.

Pathological Mechanism of Coronary Artery Disease. Coronary atherosclerosis is part of systemic atherosclerosis. Its basic cause is the deposition of cholesterol in the arterial wall, leading to a series of pathological changes. The lesions often cause thickening of the arterial intima, forming plaques. Because their surface sometimes resembles viscous rice porridge, they are called atherosclerotic plaques. 1. Coronary artery stenosis leads to insufficient myocardial blood supply. Thickening of the arterial intima and plaques both cause narrowing of the coronary vessels, resulting in restricted myocardial blood supply. When the myocardium's demand for blood supply increases, or during arterial spasm, the supply-demand imbalance becomes prominent, leading to myocardial ischemia and causing "pain" or discomfort. 2. Plaque rupture leads to thrombosis. Atherosclerotic plaques are composed of varying amounts of fibrous tissue, lipid-rich foam cells, and extracellular lipid deposits. Based on the amount of fat in the plaque and the thickness of the fibrous cap, plaques can be roughly divided into hard plaques and soft plaques. Hard plaques are relatively stable and less prone to rupture. Conversely, soft plaques are rich in fat, have thin fibrous caps, and are unstable, making them prone to rupture. When blood pressure fluctuates, blood flow forces change, or arterial spasms occur, the fibrous cap ruptures, releasing lipids into the blood vessel, inducing platelet aggregation and thrombosis, leading to unstable angina or myocardial infarction. Soft plaques are the most important basic pathological change in the prevention and treatment of cardiovascular and cerebrovascular diseases. It has been reported that although these soft plaques account for only about 10% of all atherosclerotic plaques, they are the cause of 80%–90% of acute coronary syndromes or myocardial infarctions. More seriously, in most cases, soft plaques rupture suddenly without any warning signs.

Factors that trigger angina and myocardial infarction: 1. Biological cycle changes in the human body. The body's physiological activities, such as blood pressure and heart rate, exhibit diurnal cycle changes. These changes make plaques more prone to rupture between 6:00 AM and 11:00 AM. This is why most myocardial infarctions occur in the early morning. 2. Physical and mental overexertion. Excessive exercise, physical or mental labor, leading to overwork and stress, increases the heart's oxygen consumption. Vascular spasm reduces oxygen supply and can even cause plaque rupture, inducing thrombosis. 3. Emotional excitement. Excitement, tension, and anger are closely related to the onset of the disease. 4. Overeating. This is one of the important reasons for the high incidence of myocardial infarction during holidays. Overeating during holidays, a sharp increase in blood lipids, excessive smoking, and drinking can lead to coronary artery spasm, thrombosis, and myocardial infarction. 5. Constipation. 6. Other diseases. Stroke, dehydration, massive hemorrhage, shock, surgery, respiratory infection, fever, hypoxemia, hypoglycemia, tachycardia, etc.