Among the chronic diseases in my country, the morbidity and mortality of cardiovascular and cerebrovascular diseases have always been the highest.

In order to prevent and reduce the occurrence of cardiovascular and cerebrovascular diseases and their adverse events, lipid-lowering therapy is an important part of it.

But in reality, some patients take medicines irregularly, and some patients take medicines ineffectively. Therefore, the medical community has been researching more effective blood lipid lowering methods.

Recently, many people have asked about a new type of "blood lipid-lowering vaccine" called Inclisiran, which is said to be "one injection for half a year". Is there such a convenient and effective treatment method?

What else do we need to know about lipid lowering?

  "Vaccine" is a new type of lipid-lowering targeted drug

  At present, my country has entered an aging society, and the number of people with cardiovascular and cerebrovascular diseases is increasing.

For the two lipid-lowering treatments, long-term medication and injections, the latter is easier to accept for many people with poor medication compliance.

So, can injections to lower blood lipids be promoted?

  In fact, Inclisiran is not a "vaccine" that can prevent diseases as everyone understands, but a targeted therapy drug that lowers LDL-C (low-density lipoprotein cholesterol, commonly known as "bad cholesterol"), which has been clinically tested one after another. Phase I, II, and III trials have obtained data on the safety and efficacy of lipid-lowering, and it will be launched in Europe in 2020, but it has not yet been approved for marketing in my country.

  Inclisiran, approved and marketed in Europe, is used for lipid-lowering therapy for secondary prevention of cardiovascular disease (Secondary prevention of cardiovascular disease: early detection, early diagnosis, early detection of coronary heart disease and other atherosclerotic vascular diseases in patients Treatment, the purpose is to improve symptoms, prevent disease progression, improve prognosis, reduce mortality and disability, and prevent disease recurrence).

At the end of December 2021, the U.S. Food and Drug Administration also approved Inclisiran for the treatment of heterozygous familial hypercholesterolemia and atherosclerotic cardiovascular disease.

  Inclisiran is a chemically synthesized small interfering ribonucleic acid (siRNA), which can bind to the messenger RNA (mRNA) of PCSK9 protein in liver cytoplasm and degrade it, thereby inhibiting the expression of PSCK9 protein, and ultimately reducing blood low-density lipoprotein. Cholesterol levels.

  Previous studies have confirmed that Inclisiran can reduce the level of low-density lipoprotein cholesterol by about 50%; at the same time, it can reduce the level of intracellular and extracellular PCSK9 protein, thereby significantly reducing the concentration of low-density lipoprotein cholesterol for a long time.

In clinical treatment, only subcutaneous injections are required every 3-6 months, and the patient's medication compliance is expected to improve.

  Based on currently disclosed information, Inclisiran is indicated for patients with primary hypercholesterolemia, as a combination therapy based on dietary and lifestyle interventions and taking maximum tolerated doses of statins, and for patients with statin intolerance monotherapy.

  However, since the safety and efficacy of Inclisiran need to be further confirmed by clinical trials with larger samples, it is too early to talk about a large-scale promotion.

  Why doctors favor statins

  Currently, oral lipid-lowering drugs are still the first-line treatment for blood lipid lowering worldwide. What are the pros and cons of these lipid-lowering drugs?

What about the development trend?

  For patients with dyslipidemia, whether to initiate lipid-lowering drug therapy must be determined by doctors based on comprehensive consideration of factors such as their condition, cardiovascular disease risk stratification, and organ function.

Some of these patients need to make lifestyle changes, such as smoking cessation, alcohol restriction, moderate exercise, weight control, diet adjustment, etc., and then evaluate whether to take lipid-lowering drugs.

Therefore, when dyslipidemia is found, patients are advised to seek medical attention first, rather than self-medication.

  It is well known that low-density lipoprotein cholesterol is the "culprit" of atherosclerotic cardiovascular disease.

Regardless of domestic or international guidelines, statins are the preferred lipid-lowering drugs, which play a lipid-lowering effect by inhibiting HMG-CoA reductase and reducing the synthesis of cholesterol in the body, especially low-density lipoprotein cholesterol.

  There are many statins commonly used in clinic, including atorvastatin, rosuvastatin, pitavastatin, fluvastatin, pravastatin, simvastatin, lovastatin, etc., according to the cardiovascular risk stratification of patients and blood lipid levels.

Among them, atorvastatin and rosuvastatin are potent statins; pitavastatin, pravastatin, and simvastatin are moderate-acting statins; and fluvastatin is less effective.

Under normal circumstances, according to the lipid-lowering efficacy, adverse reactions or tolerance, the dose or type of drugs will be adjusted during use.

  How to avoid side effects like liver damage

  In outpatient clinics, patients are most concerned about liver damage or muscle toxicity caused by statins, and there are many patients who are reluctant to take drugs because of fear of adverse reactions.

However, poor control of blood lipids may lead to cardiovascular and cerebrovascular diseases, and even life-threatening.

Therefore, the correct way is to take the medicine as prescribed by the doctor and monitor the physical condition regularly.

For example, 4-6 weeks after starting the drug or adjusting the regimen, review the biochemical blood lipids, transaminases, creatine kinase and other indicators; at the same time, pay attention to whether you have symptoms such as nausea, loss of appetite, liver discomfort, muscle pain or fatigue, etc., and seek medical attention in time Notify your doctor.

  In addition, there may be interactions between statins and other drugs.

Atorvastatin, simvastatin, lovastatin are mainly metabolized by liver CYP3A4 (an important enzyme in the body), and are easily combined with some CYP3A4 inhibitors (such as clarithromycin, itraconazole, cyclosporine, etc.) Interactions occur, increasing the blood concentration of statins, thereby increasing the risk of liver damage and myopathy.

It is recommended that you inform your doctor of all the medicines you take, including health products, when you visit your doctor.

  Attention should be paid to taking statins: those who are allergic to the drug should stop the drug immediately; take the drug strictly according to the doctor's advice, and do not stop or change the drug at will; Guide medication; adhere to a reasonable diet, moderate exercise, and cannot lower blood lipids only by taking medication, otherwise it will be difficult to receive good therapeutic effects.

  What situations require alternative medicines

  Due to individual differences, some patients were intolerant to statin lipid-lowering drugs or had serious adverse reactions. After taking the drugs, the indicators such as transaminase and creatine kinase were abnormally increased.

For such patients, doctors will give alternative medicines. There are 3 kinds of alternative medicines commonly used at present, which are selected according to the patient's condition.

  1. Ezetimibe Ezetimibe is a cholesterol absorption inhibitor and has a good effect on lowering LDL cholesterol.

For some patients who are intolerant to statins or have serious adverse drug reactions on statins, ezetimibe can be selected for lipid-lowering therapy.

In some patients, statins alone fail to achieve lipid-lowering goals, and the addition of ezetimibe for synergistic lipid-lowering may also be considered.

  It should be noted that the adverse reaction of ezetimibe may also occur during the use of elevated transaminase, but it is not necessary to stop the drug immediately when this occurs.

  2. Fibrates Fibrates can significantly reduce the level of triglyceride (TG) in the blood, and its effect on reducing triglyceride is stronger than that of low-density lipoprotein cholesterol.

Studies have shown that fibrates can reduce low-density lipoprotein cholesterol by 20%, increase high-density lipoprotein cholesterol by 5%-20%, and reduce triglycerides by 25%-50%.

The commonly used drug in fibrates is fenofibrate. According to the patient's dyslipidemia, fenofibrate can be used alone or in combination with statins.

  However, it should be noted that fenofibrate has certain muscle toxicity, so when it is used in combination with statins, it is best to take it at separate times, such as taking fenofibrate in the morning and taking statins in the evening.

  3. PCSK9 inhibitors (evolumab, aliximab) In fact, there are currently clinically subcutaneously injected lipid-lowering drugs PCSK9 inhibitors, which can selectively bind to circulating PCSK9 (pro-protein convertase subtilis). Lysin Kexin9 type, when this enzyme is active, the body's "bad cholesterol" low-density lipoprotein cholesterol will rise), reduce the concentration of PCSK9 in serum, and increase the number of low-density lipoprotein receptors, which can greatly reduce blood levels. Low-density lipoprotein cholesterol levels.

In recent years, a series of studies have confirmed the role of PCSK9 inhibitors in the secondary prevention of atherosclerotic cardiovascular disease.

For those who fail to achieve good lipid-lowering effect or fail to reach the target (including patients with familial hypercholesterolemia) using traditional lipid-lowering drug therapy, have serious adverse drug reactions that require drug discontinuation, and are intolerant to statins and other drugs, they may be considered Add or switch to PCSK9 inhibitors.

Commonly used PCSK9 inhibitors are elocumab and alecizumab, which are administered by subcutaneous injection, usually every 2 weeks or once a month.

  Finally, let’s sort out the use of these three types of drugs: for the secondary prevention of atherosclerotic cardiovascular disease, statin lipid-lowering drugs are generally preferred; if patients cannot tolerate any type and dose of statins For patients with severely elevated triglyceride levels (ie, TG ≥ 5.6 mmol/L), fibrates may be the first choice to reduce the risk of acute pancreatitis. When TG is less than 5.6mmol/L, statins should be added as appropriate.

  Finally, we would like to remind everyone that no matter whether you take lipid-lowering drugs or not, you must insist on controlling your diet and improving your lifestyle. These two points are the basis for the treatment of dyslipidemia.

  Wang Huaguang (Author: Chief Pharmacist of Beijing Chaoyang Hospital Pharmacy Department)