Statins – Interesting Facts

Statins, or HMG-CoA reductase inhibitors, are lipid-lowering drugs. One of the most common drugs used to lower low-density lipoprotein cholesterol. Taking statins from the moment of appointment is required for life without interrupting the course.

In most cases, statins are well tolerated by patients, but sometimes side effects can occur with medication. Most often, patients complain of headache and light muscle pain, as well as nausea.

The list of international non-proprietary names for statins includes lovastatin, rosuvastatin, atorvastatin, simvastatin, pitavastatin, pravastatin and fluvastatin. There are also combination drugs with statins, such as a statin with a cholesterol absorption inhibitor.

Atorvastatin and simvastatin are included in the list of vital and essential medicines for medical use for 2020 in the Russian Federation.

Mechanism of Action

Cholesterol is required by the body to create all the steroid hormones, vitamin D, and bile acids that help digest food. About 75% of cholesterol is produced by liver cells, and 25% is ingested with food. There are two types of cholesterol: low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Sometimes, due to lifestyle, genetics or dietary habits, the level of “bad” cholesterol in the blood rises, which increases the risk of developing cardiovascular disease. The reason for this is the ability of “bad” cholesterol to combine with other substances in the body and form hard deposits on the inner walls of arteries, which are called atherosclerotic plaques. The plaques constrict the lumen of the vessels, making them less flexible. Sometimes plaques rupture, which can lead to coronary artery disease, myocardial infarction, and other diseases of the cardiovascular system.

Statins reduce the synthesis of “bad” cholesterol in the liver and, accordingly, its concentration in the blood. Thus, the action of the drug reduces morbidity and mortality from cardiovascular diseases.

Indications

The ability of statins to lower levels of “bad” cholesterol and reduce inflammation of the vascular walls helps reduce the risk of developing certain cardiovascular diseases or their complications. Studies show a 21% reduction in the risk of developing all major cardiovascular events, such as myocardial infarction and strokes. Usually, statins are taken for life in the absence of serious side effects.

People without cardiovascular disease

According to the American College of Cardiology (ACC) and American Heart Association (AHA) guidelines for primary prevention of cardiovascular disease in 2019, people between 20 and 75 years old, the tests of which show very high levels of low-density lipoprotein cholesterol – more than 190 mg / dl (or more than 4.90 mmol / l), statin therapy should be prescribed immediately. To decide whether to prescribe statins for patients without symptoms of cardiovascular disease, doctors assess the individual’s risk of developing these diseases. To do this, first identify risk factors: smoking, hypertension (high blood pressure), diabetes mellitus, dyslipidemia (increased levels of “bad” cholesterol and / or low levels of “good” cholesterol), obesity, pay special attention to family history of cardiovascular vascular diseases in relatives at a young age (in men under 55 and in women under 65).

Patients from 40 to 79 years old are then asked to determine the likelihood of developing cardiovascular disease at different horizons using standard calculators – more often within 10 years, but it is possible to estimate the risk within 30 years. To calculate the degree of risk, it is necessary to indicate age, sex, cholesterol (total, low and / or high density lipoprotein), systolic and diastolic blood pressure values, smoking history, and some include questions about the presence of diabetes mellitus and the use of drugs (acetylsalicylic acid, statins and / or drugs that lower blood pressure). As a result, the calculator gives an approximate estimate: for example, in the model of the American College of Cardiology (ACC) and the American Heart Association (AHA), a value of less than 5% is assigned to a low risk, from> 5% to <7.5% to a borderline risk, and an average -> 7.5% to <20% and to high – more than 20%.

According to the recommendations of The US Preventive Services Task Force (USPSTF), low- to moderate-dose statin therapy may be considered in people aged 40 to 75 years who have one or more risk factors (dyslipidemia, diabetes mellitus, arterial hypertension or smoking), as well as with an estimated risk of developing cardiovascular diseases of 10% or more. Therapy for people with a 7.5% to 10% risk has less potential benefit and should therefore be discussed individually between specialist and patient.

The American College of Cardiology (ACC) and American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease for 2019 use statin therapy for patients at 7.5% risk without diabetes aged 40 to 75 and with a low density lipoprotein cholesterol level of 70 mg / dL to <190 mg / dL. For those at borderline risk (5% to <7.5%), statin therapy can be discussed if there are other risk factors.

Assessment of the risk of developing cardiovascular diseases for people under 40 is not routinely carried out, but anyone can independently seek advice from a specialist to calculate the long-term risk. For example, if his immediate family (parents, brothers or sisters) has premature heart disease, or he has familial hypercholesterolemia, early onset type 2 diabetes mellitus or type 1 diabetes mellitus, multiple risk factors are noted at an early age, and also if there are signs suggesting the possible presence of atherosclerosis, identified by examining the calcium content in the coronary arteries. The decision on statin therapy in this case is determined individually.

For patients over 79 years old without established cardiovascular diseases, the decision on preventive therapy should be made together with a doctor, assessing its benefits and risks individually.

People with cardiovascular disease

For people with known cardiovascular disease, such as angina pectoris, coronary artery disease, myocardial infarction, stroke, and / or peripheral arterial disease, statins are prescribed to prevent worsening or recurrence of these conditions. Studies show that when the level of “bad” cholesterol is reduced to less than 70 mg / dL, the size of the plaques in the arteries can decrease. Patients after myocardial infarction and / or surgery on coronary arteries can be prescribed statins even with normal cholesterol levels.

Familial hypercholesterolemia

Patients with familial hypercholesterolemia develop very high levels of low-density lipoprotein cholesterol from birth, placing them at high risk for early development of cardiovascular disease. In this case, experts recommend dietary and lifestyle changes, mandatory regular physical activity, and lifelong statin therapy. When confirming the diagnosis of familial hypercholesterolemia in a child, statin treatment is advised to begin at the age of about 10 years.

People with diabetes

Patients with type 1 or type 2 diabetes have an increased risk of developing cardiovascular disease. To reduce it, they need to constantly monitor their blood glucose levels, try to lead a healthy lifestyle, and in addition, most people with diabetes need to take cholesterol-lowering drugs, that is, statins. According to the medical database UpToDate, they are prescribed for patients over 40 years of age or with multiple risk factors for cardiovascular disease (for example, a family history of cardiovascular disease, high cholesterol, high blood pressure, or obesity). Statins reduce the risk of myocardial infarction, stroke and premature death, even if a person’s cholesterol levels are normal.

Side effects

Prevalence

In most cases, statins are safe for patients when used at the recommended doses. But like any medication, statins have a number of side effects. Common and common to different types of these drugs include the following adverse events: headache, dizziness, weakness, problems with the digestive system (constipation, diarrhea, indigestion, flatulence), muscle pain, trouble sleeping.

Some of the non-standard side effects that can occur with certain types of statins are: tingling or numbness, such as in the limbs, hair loss, decreased libido, skin rashes, inflammation of the liver or pancreas. Some side effects may subside over time as the body adjusts to the treatment. The doctor can change the medication or change its dosage if the side effects persist and interfere with normal life.

Rarely, statins can increase the risk of type 2 diabetes, increased liver enzymes, or serious muscle damage. It is important to understand that the benefits of statins generally outweigh the risks of using statins in patients with indications for these drugs. If any undesirable phenomena occur, consult a doctor.

Cognitive Function

Some patients on statins report problems with cognitive function – memory loss and confusion. Research on this topic has so far been highly controversial, with some showing a reduction in long-term risk of developing, for example, dementia, while others point to negative, but reversible and short-term effects on memory. Doctors note that further research is needed on this topic with the help of large randomized controlled trials.

Muscle pain

Muscle pain is a common side effect of statins, but placebo-controlled studies do not support the conclusion that statin use is responsible for this symptom. In observational studies, where people know that they are taking statins and evaluate the side effects of this particular drug, complaints of muscle pain are quite common (10-15% of the subjects). In contrast, data from placebo-controlled studies show no or a slight increase in the incidence of muscle side symptoms during statin therapy. Scientists attribute this to the “nocebo” effect – when a symptom is triggered by negative expectations about taking the medicine.

In rare cases, mild muscle pain can progress and accompany the development of serious diseases, such as myopathy or rhabdomyolysis. If myopathy is suspected, your doctor may order a blood test to check your creatine kinase levels. Rhabdomyolysis is a severe muscular side effect that can occur with statin use. However, the incidence is approximately 1-3 cases per 100,000 patients per year. Overall, the risk of serious muscle-related side effects is less than 0.1%.

Diabetes mellitus

Several studies show that patients on statin therapy may have a slightly higher risk of impaired carbohydrate metabolism and the development of type 2 diabetes. The likelihood of this event is increased if the person had an elevated blood sugar level prior to statin therapy. But the reduced risk of developing cardiovascular disease outweighs this potential side effect.

Liver dysfunction

Alanine aminotransferase (ALT) levels are measured to determine the extent of liver damage. A moderate increase in ALT is observed in 0.5-2.0% of patients receiving statin therapy. Most often this is due to the type of statin molecule or high doses of the drug. Studies conclude that such a moderate increase in ALT is not associated with changes in liver function. The progression of such pathological conditions to liver failure in people without special medical conditions is extremely rare, therefore the standard regular monitoring of ALT levels during treatment with statins is not recommended.

Interactions with drugs and food

Some statins can interact with other drugs, such as clarithromycin, protease inhibitors (may be included in the treatment of human immunodeficiency virus (HIV) and hepatitis C), cyclosporine, gemfibrozil, oral contraceptives, and digoxin. For example, concomitant use of HIV or HCV protease inhibitors with certain statins may increase the risk of myopathy and / or rhabdomyolysis. HIV protease inhibitors or hepatitis C virus inhibitors are contraindicated with lovastatin and simvastatin.

Grapefruit juice increases the concentration of atorvastatin, lovastatin, and simvastatin, which can increase the risk of side effects, so it should be avoided while taking these statins (or eating no more than half a grapefruit per day). Patients who abuse alcohol also increase the risk of serious side effects with statin therapy.

Use during pregnancy

The use of statins is contraindicated in pregnant and lactating women, since there is no convincing evidence of their safety during these periods.

Classification

The list of international non-proprietary statins includes lovastatin, rosuvastatin, atorvastatin, simvastatin, pitavastatin, pravastatin and fluvastatin (cerivastatin was withdrawn from the market in 2001 due to side effects). There are also combination drugs with statins, such as a statin with a cholesterol absorption inhibitor.

Statins differ in terms of lowering total cholesterol, low-density lipoprotein cholesterol, or raising high-density lipoprotein cholesterol, as well as their tendency to interact with drugs and have some side effects.

Alternative to statin therapy

Preparations

Statins are the most studied and most commonly used class of drugs for lowering low-density lipoprotein cholesterol and lowering the risk of cardiovascular disease. If the target lipid levels are not achieved with statins, or if the patient has a statin contraindication that prevents the use of these drugs, the doctor may prescribe ezetimibe, PCSK9 inhibitors, or bile acid sequestrants. Standard omega-3 supplements have not shown significant benefits and are therefore not recommended.

Lifestyle changes

Lifestyle can greatly influence blood cholesterol levels, so it is important to eat a healthy diet, exercise regularly, maintain a healthy weight, and get rid of bad habits when taking statins.

Nutritionists advise to add more vegetables, fruits, fish and whole grains to the diet, avoid saturated fats and trans fats, high amounts of salt (no more than 5-6 grams per day) and sugar (no more than 30 grams). You can follow the nutritional guidelines from the UK NHS. They suggest using a visual diagram: a little more than a third of your plate should be occupied by vegetables and fruits, another third – carbohydrates (potatoes, rice, whole grain pasta and various cereals) and the rest is divided into protein (meat, fish, legumes, eggs) and dairy products ( milk, fermented baked milk, cheese, cottage cheese), as well as a small amount of unsaturated fats.

Physical activity should be done every day and include strength and aerobic exercise. Strength elements are anything that can strengthen your muscles, like squats and push-ups or gardening. It is better to do them at least 2 times a week. Aerobic includes everything that warms up the body and increases the heartbeat – brisk walking in the city, football, dancing, cycling, and more. And divide them into exercises with moderate or high intensity. During the performance of the first, a person is able to talk (as when riding a bicycle on a flat surface), and they need to spend at least 150 minutes a week on them, and with the latter, it is already difficult to talk, as when running, and you can devote them 75 minutes a week.

Before prescribing statins, doctors may ask the patient to make lifestyle changes to check how their cholesterol will respond. Sometimes it’s enough to lower your low-density lipoprotein cholesterol.