Statins

summary statins

Statins are a class of drugs with a lipid-lowering effect. They can treat high cholesterol , mainly by lowering the level of “bad” cholesterol (LDL-C or LDL). Statins have a preventive role, with the aim of reducing cardiovascular risk. Statin treatment is commonly for life.

Mechanism of action

Statins are HMG-CoA reductase inhibitors. This enzyme is responsible for the synthesis of cholesterol in human cells.

Effects

After taking statins, a significant decrease in blood levels of LDL (“bad cholesterol”), a slight reduction in triglycerides and a moderate increase in levels of HDL (“good cholesterol”) were observed. Low levels of LDL and triglycerides reduce the formation of atheromatous plaque (plaque that can clog arteries, leading to cardiovascular complications).

It should be noted that there is no controversy over the pharmacological (LDL) lowering effect of statins. Controversy (see below) lies more in whether or not lowering LDL and triglycerides has an effect on reducing cardiovascular risk in the patient and whether or not atheroma forms are due to elevated LDL.

Some scientists believe that controlling cholesterol levels (especially LDL) helps prevent cardiovascular diseases (infarction, stroke, etc.). Some, however, are much more critical of the utility of statins on a large scale (see below). It is also notable that the vast majority of physicians in the world believe that lowering LDL reduces cardiovascular risk.

Indications

– Statins are used to prevent cardiovascular disease. In medicine we distinguish primary prevention from secondary prevention. Primary prevention means that the patient has not had any cardiovascular disease in the last few months. The secondary prevention indication is for the patient who has suffered in the past from some cardiovascular disease, such as a heart attack ,  stroke , angina pectoris , etc.

Statins are especially indicated in cases of secondary prevention, but they can also be prescribed for primary prevention, especially in cases of high cholesterol (LDL, triglycerides). However, the Haute Autorité de Santé (HAS) in France considers that there is an overprescription of statins in primary prevention.

Large Study of High LDL Levels
A study published in 2018 in JAMA,showed that people with a high level of LDL (> 100 mg/dl) could significantly benefit from the use of statins to combat cardiovascular events (eg stroke, heart attack). This research work focused on the analysis of several studies published in the past (meta-analysis), including more than 270,000 patients. The study was mainly conducted by Prof. Jennifer Robinson from the University of Iowa (United States). The researchers came to the conclusion that 4.3 out of every 1000 people have their lives saved each year when they are treated with a treatment to lower LDL cholesterol levels, such as the use of statins. The greatest benefit and the greatest reduction in mortality rates were seen in those with the highest levels of LDL cholesterol, according to Prof. Robinson in a study press release published in April 2018. The analysis revealed that statins were more likely to reduce the risk of death when LDL cholesterol was 100 mg/dl or higher, whether or not statins were used with other hypolipidemic drugs. This study was published on April 17, 2018 in the scientific journalJournal of the Amercian Medical Association ou JAMA (DOI: 10.1001 / jama.2018.2525).

– A study published in 2014 showed that statins can reduce nerve damage in cases of  multiple sclerosis . These drugs also act on physical disturbances in cases of multiple sclerosis in a secondary progressive way.

– A study published in February 2015 showed that statins can reduce the risk of liver cancer . According to the researchers, the regular use of statins can be especially useful in patients at high risk of liver cancer, such as those with chronic liver diseases (hepatitis B or C, for example) or diabetes. This study was published February 26, 2015 in the online version of the Journal of the National Cancer Institute .

Statins and cancer
– A large observational study carried out by Aston Medical School with more than 900,000 patients in Great Britain showed that high cholesterol levels in cancer patients would be the origin of a decrease in the mortality rate of 4 common types of cancer: cancer breast , lung , prostate and colon / rectum (colorectal cancer)🇧🇷 British scientists found that people who had high cholesterol levels (hypercholesterolemia) had a 22% lower risk of lung cancer mortality than those with normal cholesterol levels. In the same logic, in cases of breast cancer the risk of mortality reduced by 43%, in prostate cancer the reduction was 47% and in colon / rectum it was 30%. According to the scientists, this decrease would be caused by the use of statins. The scientists say these results reinforce the case for conducting a clinical trial evaluating the possible protective effect of statins, other commonly used cardiovascular drugs (such as aspirin) and antihypertensive drugs in cancer patients.European Society of Cardiology ), held July 8-10, 2016 in Florence, Italy.

Main molecules of the statin family

Atorvastatin (see below in comments), simvastatin, pravastatin, fluvastatin, rosuvastatin, lovastatin (which comes from red fermented rice) are examples of molecules in this class. Lovastatin was the first statin on the market. Note that statins are usually associated with a salt, for example atorvastatin calcium trihydrate.

Some sources estimate that atorvastatin and rosuvastatin have a superior effect than other statins, that is, they can be used to lower LDL more effectively. According to the French journal Prescription, known to be neutral towards the pharmaceutical industry, if the doctor prescribes a statin he must choose between pravastatin or simvastatin. Still according to the journal, pravastatin is the first choice in case of risk of drug interactions.

(Galenic) forms of statins

Statins are sold primarily in pill or capsule form.

Dosage, time to take statins (chronotherapy)

Statins are usually taken once a day, i.e. 1 tablet or capsule a day. The production of cholesterol by the liver is highest after midnight and lowest in the morning as well as in the early afternoon. That’s why certain experts recommend taking statins at night before bed. However, each statin has a different dosage, with certain statins that can be taken at any time of the day and regardless of meals, so read the package insert before taking a statin. However, it is important for all statins to always take them at the same time of day, that is, avoid taking a statin one day at noon and another at night, for example.

Which statin to choose?

The choice of statins falls in the hands of the physician. All statins are used to lower LDL. There may be some differences between statins, such as bioavailability, price, etc.

2018 study
According to a Swiss study published by the University of Zurich on December 4, 2018 in the scientific journal Annals of Internal Medicine (DOI: 10.7326/M18-1279), atorvastatin and rosuvastatin have a better relationship between benefits and the side effects that simvastatin and pravastatin.

Side effects

side effects of statins

Contraindication

Some statins are contraindicated in pregnancy, lactation, certain liver diseases, etc. For a complete list, read the medicine’s package insert.

Drug interactions

Some reported interactions are with fibrates, cyclosporine, macrolide antibiotics (in this case, it is important to stop taking statins if antibiotic treatment lasts longer than 10 days). In all cases of statin treatment, read the package insert and ask your doctor or pharmacist.

allergies

Statin allergy affects approximately 1.5% of both men and women, according to a study published in September 2016 (print version) in the specialist journal Allergy . The number of people with allergies doubled between the early 2000s and 2013. The study was conducted under the direction of Dr. Li Zhou of Brigham and Women’s Hospital   in Boston (MA), USA.

Consumption

    • In Brazil, it is estimated that 8 million people use statins (2013).
    • In the United States, an estimated 36 million people use statins (2013). An August 1, 2017 Wall Street Journal article estimated that 56 million Americans should theoretically be taking statins. In the United States, an article in Prevention magazine estimated the annual cost of statins in 2017 to the US health system at 17 billion dollars.
    • In the UK, an estimated 5.2 million people use statins (2013).
    • In France, around 5 to 6 million French people consume statins (2013).
  • Globally, an estimated 1 billion people take statins. However, this last statistic is difficult to verify, and is a theoretical and not an actual number of people who should be taking statins worldwide.

The controversy surrounding statins

 

In some countries, particularly France, there are controversies about statins. Professor Phillip Evans has published a book, “The Truth About Cholesterol”, in which he is very critical and believes that in most cases, the preventive use of statins to lower cholesterol is useless, because it does not reduce the mortality rate. According to this author, in most cases, lowering bad cholesterol (LDL) does not reduce cardiovascular risk, since LDL are not generally responsible for the formation of atherosclerosis in the arteries. Other French professors believe that Professor Evan exaggerates and think it is important to use statins, at least in some patients.
The values ​​and financial issues surrounding these treatments are so great that you can imagine that the pharmaceutical industry tends to influence the prescription of statins.
At the moment, it is difficult to see clearly this controversy, because there are several studies that are somewhat contradictory. Ask your doctor or pharmacist about the benefits of taking statins. Note, however, that the vast majority of cardiologists around the world recognize the usefulness of statins to reduce cardiovascular risk, and it is no wonder that statins are among the most prescribed drugs in the world.

In November 2013, two prestigious American members of the scientific society, the American Heart Association  (HAA) and the American College of Cardiology  (ACC), modified their recommendations (guideline) on the prescription of statins. To summarize, LDL (bad cholesterol) level was no longer considered as a treatment goal, clinicians should also include the overall cardiovascular risk for each patient, taking into account each heart disease. In 2013, the estimated number of Americans taking statins was 36 million. However, this decision was not unanimous at the time, some experts from the Harvard Medical School, another leading institution, created a scandal, perhaps because it saw a pharmaceutical industry lobby behind this favorable decision for statin manufacturers.

However, according to a study published in the scientific journal Journal of the American Medical Association in July 2015, these recommendations proved to be more accurate and effective than those established before 2013, mainly because they allow identifying adults at high cardiac risk. This decision would have enabled or saved thousands of lives, according to Dr. Udo Hoffmann, the researcher who led this research, who expressed himself through a statement from the Massachusetts General Hospital from Boston: “Extrapolating the results of the approximately 10 million Americans who would then be eligible for statin therapy under the 2013 recommendations, it is estimated between 41,000 and 63,000 the number of cardiovascular events – heart attack, stroke or death from cardiovascular disease – which can be prevented within a 10-year period”.

Comments

– Muscle-type adverse effect is the main reason for discontinuing statin therapy.

– Coenzyme Q10 does not appear to have been scientifically proven to reduce muscle-type side effects in those taking statins.

– We know that statins are among the most prescribed and most profitable drugs for the pharmaceutical industry. Worldwide, it is assumed that the cholesterol drug market represents a turnover of more than $25 billion a year, largely from statins. In fact, they are considered by physicians (especially cardiologists) to be the most effective class of LDL-lowering drugs.

– It is estimated that, in patients who have already suffered from a cardiovascular disease, such as a heart attack or stroke, the use of statins reduces total mortality by about 10% to 25%.

– The first statin to enter the US market was lovastatin in 1987.

The Success of Lipitor (Atorvastatin)

For over 10 years, Lipitor (brand name in the United States) was the drug that had the highest annual turnover of the entire pharmaceutical industry, or more than 12 billion dollars a year. Lipitor is considered the most profitable drug of all time, and since its acquisition by the company Pfizer Warner-Lambert in 2000, it has generated an impressive turnover of 131 million dollars. This drug is known as a blockbuster, or bestseller.

At the end of 2011 Lipitor’s patent expired and now it is possible to find the generic in pharmacies under the name of atorvastatin, which significantly reduced Lipitor’s turnover.

Jeanne Kenney
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I’m a stylist trainer, a content creator, and an entrepreneur passion. Virgo sign and Pisces ascendant, I move easily between my dreams, the crazy world I want, and my feet on the ground to carry out my projects.

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