Guidelines for Achieving and Managing Lipid-Lowering Therapy to Fully Achieve Target Results in Long-Term Treatment: Combination Therapy

How should lipid-lowering therapy be administered to patients with dyslipidemia and coronary heart disease?

Patients with dyslipidemia develop coronary heart disease because lipids accumulate on the walls of the coronary arteries, forming plaques and causing narrowing. Therefore, dyslipidemia is a significant risk factor for coronary heart disease. Numerous clinical studies have demonstrated that long-term, targeted lipid-lowering therapy can stabilize or reduce coronary atherosclerotic plaques, decrease coronary artery stenosis, and improve myocardial blood supply. For example, a 1%–2% reduction in coronary artery stenosis can increase blood supply by 20%–30%. After receiving lipid-lowering therapy, patients with coronary heart disease may experience a reduced incidence of myocardial infarction and sudden death, and may require fewer coronary artery stenting procedures or coronary artery bypass grafting.

How to conduct lipid-lowering therapy?

① Target lipid levels must be reached to achieve satisfactory results.

② Long-term use of lipid-lowering drugs is essential; discontinuation can lead to relapse of dyslipidemia.

③ Lifestyle changes are necessary, including attention to diet and exercise.

④ For patients who do not respond satisfactorily to a single drug or even with increased dosage, it can be combined with another drug, such as adding fibrates to statins. However, the dosage should be low, and close monitoring for adverse reactions (myopathy and elevated transaminases) is crucial.

⑤ Treatment must be individualized, meaning the dosage should be determined based on the individual's dyslipidemia and risk of coronary heart disease.

Why are lipid-lowering drugs so important for the prevention and treatment of coronary heart disease?

The main component of atherosclerotic plaques in coronary arteries is cholesterol. The higher the blood cholesterol level, the greater the probability of developing coronary heart disease. Animal experiments have confirmed this. Feeding experimental animals a high-cholesterol diet easily leads to the formation of atherosclerotic plaques in their arteries; conversely, feeding them a low-cholesterol diet does not. The higher the blood cholesterol level, the higher the incidence of coronary heart disease. A 10% reduction in blood cholesterol levels can decrease the mortality rate from coronary heart disease by 20%, while a 1% increase in high-density lipoprotein (HDL) cholesterol can reduce the risk of coronary heart disease by 2%–3%. Therefore, regulating blood cholesterol levels is crucial. Statins have brought good news to patients with dyslipidemia and coronary heart disease. Besides regulating blood lipids, they also stabilize plaques, enhance endothelial function, reduce inflammation, reduce thrombus formation, and lower the risk of plaque rupture and thrombus formation, thereby reducing the occurrence of events such as acute myocardial infarction and sudden death.

Combined Use of Lipid-Lowering Drugs

Why use lipid-lowering drugs in combination?

What are some common combinations? Some patients with refractory dyslipidemia often require the combined use of lipid-lowering drugs with different mechanisms of action to achieve therapeutic effects. For example, monotherapy often cannot achieve target levels for low-density lipoprotein cholesterol. To improve the target achievement rate and reduce adverse reactions, the combined use of different classes of lipid-lowering drugs is a reasonable choice. Combination lipid-lowering regimens often consist of a statin and another lipid-lowering drug. Commonly used combinations are as follows:

① Statins + fibrates;

② Statins + ezetimibe;

③ Statins + niacin;

④ Statins + bile acid sequestrants.

What are the advantages and disadvantages of using statins and fibrates in combination?

This combination is suitable for treating patients with mixed dyslipidemia, aiming to significantly reduce TC, LDL-C, and TG levels, and significantly increase HDL-C. It is especially suitable for patients with dyslipidemia and atherosclerosis, and is even more beneficial for patients with dyslipidemia due to diabetes and metabolic syndrome. The disadvantages of this combination include elevated liver transaminases, myalgia, myositis, and even rhabdomyolysis. Therefore, when using this combination, it is advisable to start with a low dose, taking fibrates in the morning and statins in the evening, and regularly monitoring liver function and creatine kinase levels, paying close attention to any myalgia. Additionally, avoid combining with liver enzyme inhibitors, such as macrolide antibiotics, antifungals, and cyclosporine. The risk of myopathy is relatively high when gemfibrozil is used in combination with statins.

What are the advantages and disadvantages of using statins in combination with ezetimibe?

The combination of statins and ezetimibe works synergistically on cholesterol absorption and production, improving the achievement rate of lipid-lowering therapy. It is well-tolerated; a small dose of ezetimibe combined with statins can significantly enhance the lipid-lowering effect, achieving the effect of high-dose statins, without the risk of adverse reactions associated with high-dose statins. Therefore, when high-dose statins fail to achieve lipid-lowering targets, adding ezetimibe is currently the best option. Data shows that doubling the dose of statins alone only reduces LDL-C by 6%, while adding 10mg of ezetimibe to statin therapy can reduce LDL-C by approximately 25%, equivalent to the effect of tripling the dose of statins. Currently, combination formulations of simvastatin and ezetimibe are available internationally. The combination of these two drugs has little impact on TG and HDL-C, and is contraindicated in patients with liver dysfunction.

What are the advantages and disadvantages of combining statins with niacin? Studies have found that adding a low dose of niacin to conventional statin therapy can synergistically further lower LDL-C. It is also more effective than statins alone in lowering TG and raising HDL-C. Combined use can further reduce the incidence of cardiovascular death, non-fatal myocardial infarction, and the need for revascularization. Clinical trials have proven the efficacy and safety of sustained-release niacin and lovastatin combination formulations, which are more conducive to achieving comprehensive lipid targets. Combined use carries the risk of increased blood glucose compared to statin monotherapy; sustained-release formulations avoid this risk, but blood glucose monitoring should still be strengthened during treatment. The risk of myopathy is lower when statins are used in combination with niacin than when statins are used with fibrates, but adverse reactions such as myopathy and liver damage should still be noted.