Cholesterol Drugs for People 75 and Older

When you need them—and when you don’t

Your body makes a waxy substance called cholesterol. You also get it from food. Your body needs it, but too much cholesterol in your blood can clog your arteries. This increases your risk of heart disease, heart attack, and death.

Statins are drugs that lower your cholesterol. But if you are age 75 or older and you haven’t had symptoms of heart disease, statins may be a bad idea. Here’s why:

Adults age 75 and older may not need statins.

Many older adults have high cholesterol. Their doctors usually prescribe statins to prevent heart disease.

But for older people, there is no clear evidence that high cholesterol leads to heart disease or death. In fact, some studies show the opposite—that older people with the lowest cholesterol levels actually have the highest risk of death.

Statins have risks.

Compared to younger adults, older adults are more likely to suffer serious side effects from using statins.

Statins can cause muscle problems, such as aches, pains, or weakness. Rarely, there can be a severe form of muscle breakdown.

In older adults, statins can also cause:

• Falls
• Memory loss and confusion
• Nausea, constipation, or diarrhea.

Often, older adults take many drugs. These can interact with statins and lead to serious problems. Side effects, like muscle pain, may increase. Statins can also cause a fatal reaction when taken with heart-rhythm drugs.

Statins may increase the risk of type-2 diabetes and cataracts, as well as damage to the liver, kidneys, and nerves.

Weigh the risks and benefits.

You and your doctor should look carefully at the risks and benefits of statins, especially if you are older and do not have heart disease.

Older people may not live long enough to get the important benefits from statins. You and your family should speak with your doctor about your health concerns. Are you more concerned about preventing a heart attack that might never happen? Or do you want to avoid side effects that can lead to frailty, injury, and memory problems?

Statins can cost a lot.

A one-month supply of statins can cost as little as $4, or as much as several hundred dollars, depending on the statin prescribed. You may also have to pay for extra tests to check for side effects.

When should older adults take statins?

You should take statins if you have had a heart attack, stroke, or mini-stroke (transient ischemic attack, or TIA). Statins can help prevent a second heart attack or stroke.

This report is for you to use when talking with your health-care provider. It is not a substitute for medical advice and treatment. Use of this report is at your own risk.

© 2017 Consumer Consumer Developed in cooperation with AMDA—The Society for Post-Acute and Long-Term Care Medicine.

04/2014

Buy Atorvastatin (Generic Lipitor) Online + Prescription

Atorvastatin (Generic Lipitor) is a statin medication to help lower bad cholesterol (LDL and triglycerides) and raise good cholesterol (HDL) when combined with a healthy diet and exercise. Atorvastatin reduces the risk of heart attack, heart disease, or stroke. Excess cholesterol and fatty substances in your blood accumulate along artery walls and decrease blood flow, making it harder for your heart to pump enough blood to supply oxygen to your body.

Atorvastatin can be prescribed for men and women to lower cholesterol, as well as children age 10 to 17 with an inherited condition that prevents them from removing cholesterol from their body normally (heterozygous hypercholesterolemia).

Do not take atorvastatin if you are pregnant, breastfeeding, or have liver disease.

Atorvastatin is the generic version of Lipitor.

Atorvastatin Prescription

Atorvastatin requires a prescription. You can renew your atorvastatin prescription at Blink Health. All generic medications sold through Blink Health Pharmacy are FDA-approved.

How Atorvastatin works

Atorvastatin is in a class of medications called statins, or HMG-CoA reductase inhibitors that lower bad cholesterol by blocking an enzyme in your liver used to produce LDL cholesterol. They can also raise good cholesterol levels.

Take atorvastatin by mouth usually once a day, with or without food, or as otherwise directed by your doctor. Taking it around the same time every day increases effectiveness. Do not take more or less than prescribed without talking to your doctor.

Atorvastatin is an FDA-approved generic form of Lipitor. The FDA requires all generic medications have the same active ingredients and the same safety, effectiveness, dosage form, and strength as their brand-name counterpart.

Most common side effects of Atorvastatin

• Diarrhea or gas

• Heartburn

• Sore throat

• Joint, arm, or leg pain

• Memory loss or confusion

Serious side effects:

• Muscle pain or weakness

• Extreme fatigue

• Fever

• Nausea

• Chest pain

• Unusual bleeding or bruising

• Pain in the upper right side of your stomach

• Dark-colored urine

• Yellowing of your skin or eyes

• Rash, hives, or itching

• Difficulty breathing or swallowing

• Swelling in your face, lips, tongue, throat, hands, feet, legs, or ankles

• Hoarse voice

Tell your doctor about all prescriptions, over-the-counter medications, herbal supplements, and vitamins you are taking, especially:

Atorvastatin dosage information

Atorvastatin comes in these tablet doses:

Atorvastatin alternatives

Alternative statin medications include:

Could Statins Reduce the Severity of COVID-19?

On March 21, epidemiologist Haleema Shakur-Still got a WhatsApp message from Temitayo Shokunbi, a colleague at the University of Ibadan in Nigeria. He asked about starting a trial for treating COVID-19 patients with the drug hydroxychloroquine. At the time, several trials were already in the works to investigate the effectiveness of the antimalarial to counter SARS-CoV-2, the virus that causes COVID-19, so Shakur-Still didn’t think starting another one on the antimalarial would add much new information. She offered Shokunbi an alternative: test aspirin, statins, and anti-hypertensive drugs instead. These medications, Shakur-Still reasoned, could counter the intense inflammation and other tissue damage associated with COVID-19. 

A growing amount of data shows that intense inflammation, blood clots, and stroke are some of the most severe symptoms of COVID-19. Decades of research have also shown that aside from lowering cholesterol, statins decrease inflammation, reduce blood clots, and prevent damage to endothelial tissue—the thin layer of cells that line blood vessels and other organs. That tissue also appears to be affected by COVID-19. There’s also some evidence that statins act as antivirals. Because of those effects, epidemiologists such as Shakur-Still and other researchers want to see if statins could be a readily available treatment for COVID-19, a disease that has, so far, sickened more than 7.3 million people worldwide and killed 416,000.

Shakur-Still says Shokunbi told her: “Low- and middle-income countries are in for a potential catastrophe because of weak health infrastructure. Whatever can help needs to be done.”

With Shokunbi on board, Shakur-Still, who works at the London School of Hygiene and Tropical Medicine, and her collaborators got to work devising a trial that will begin in the next few weeks. In it, COVID-19 patients coming to a treatment center either in Pakistan or Nigeria will be randomly assigned to receive aspirin, the cholesterol-lowering drug simvastatin, the anti-hypertensive losartan, a combination of the drugs, or standard of care. Another trial in Cambridge, Massachusetts, will test a similar cholesterol-lowering drug called atorvastatin, and there are a few other clinical trials underway that will look at the effects of statins on COVID-19.  

“Effective treatments are needed urgently,” Shakur-Still writes in an email to The Scientist. “Even a modest reduction in mortality from an inexpensive and widely available and practicable treatment that adds little additional burden to hospital staff working in overstretched health systems would be helpful.”

Statins’ effects on inflammation and blood clots

Data to suggest that statins may reduce the severity of COVID-19 or prevent death from it are limited. A small, observational study of 150 individuals in their 80s published on medRxiv in mid-May shows that those who took statins for cardiovascular disease before coming down with COVID-19 fared better than individuals of a similar age who were not on statins. From the results, “it seems like statins are beneficial in this population, and we know they are safe and cheap,” says study coauthor Anton De Spiegeleer of Ghent University in Belgium. “And it’s all that we have.”

The results of that study also suggest that a combination of a statin and an antihypertensive drug could have even more benefit than statins alone, but more work needs to be done to confirm that link, De Spiegeleer says. David Kass, a cardiologist at Johns Hopkins School of Medicine who was not involved in the work, is more reserved about the conclusions and says there could be other reasons, such as overall health, lifestyle, or genetics, that could account for why participants on statins fared better after they became infected with SARS-CoV-2.

We have known for a long time that statins do more than lower cholesterol. It’s those other effects, the ones they weren’t designed to have but do have, that could affect the coronavirus.

—David Kass, Johns Hopkins School of Medicine

One of the consequences of severe SARS-CoV-2 infection is widespread inflammation in the lungs—also called acute respiratory distress syndrome, or ARDS. Research has shown statins can ameliorate ARDS, Shakur-Still says. Simvastatin, for example, reduced lung inflammation and lung injury in mice with ARDS. It also quelled lung inflammation in healthy human volunteers who had inhaled an endotoxin. That’s one reason she and her colleagues are testing simvastatin in their clinical trial to treat COVID-19. 

How exactly statins reduce the inflammation of ARDS isn’t clear, though studies have shown that the drugs can suppress inflammatory cytokines, such as interleukin-6, and target the cell signaling molecules so that they are broken down before entering endothelial tissue. Acting in those ways, statins could shore up the integrity of the barrier that separates the lungs’ endothelial tissue, which lines blood vessels, from their epithelial tissue, which surrounds the air sacs, or alveoli, that help us breathe. Maintaining that barrier between the tissue types would keep inflammatory molecules out of the lungs, explains David Fedson, a retired physician and former director of medical affairs at the European vaccine company Aventis Pasteur MSD. Other drugs, such as antihypertensives, might have a similar effect. This type of treatment protocol is an example of an emerging concept in infectious disease research called disease tolerance, in which treatments target the host’s response to infection, rather the virus itself.

See “Could Tolerating Disease Be Better than Fighting It?”

Along with reducing inflammation, statins might also prevent blood clots, another consequence of SARS-CoV-2 infection. A small study of 21 patients admitted to intensive care at Baylor St. Luke’s Medical Center in Houston found that more than half developed blood clots while being treated for COVID-19. In a separate study, patients who died of COVID-19 had nine times as many blood clots in their lungs as patients who died of the h2N1 flu, a team of doctors reported May 21 in the New England Journal of Medicine. Experimental studies and clinical trials have shown that statins can lower levels of thrombin, an enzyme in blood plasma that assists in blood clotting, and increase levels of thrombomodulin, a protein expressed on endothelial cells that reduces blood coagulation.

“We have known for a long time that statins do more than lower cholesterol,” Kass says. “It’s those other effects, the ones they weren’t designed to have but do have, that could affect the coronavirus. ”

Statins’ interference with SARS-CoV-2

Statins might not only target inflammation and blood clots, but interact with viruses directly as well. The drugs reduce the amount of cholesterol in the membranes of cells, and lower levels of cholesterol can prevent viruses from successfully entering cells. A study published May 10 on bioRxiv showed that added cholesterol in the cell membrane makes it easier for SARS-CoV-2 to get inside. 

When the cholesterol level in the cell membrane is high, ACE2—the receptor the virus uses to invade cells—sits at a spot on the cell surface primed for endocytosis, the process by which extracellular material (including viruses) is brought into the cell. When cholesterol is low, ACE2 is present in a region that isn’t primed for endocytosis. SARS-CoV-2 can still gain entry through a less efficient cell surface mechanism using the protein TMPRSS2, but the new work shows the endocytic pathway is the more infectious one, study coauthor Scott Hansen of the Scripps Research Institute in Jupiter, Florida, writes in an email to The Scientist. Lowering cell membrane cholesterol levels, which statins could do if taken in advance of infection, led to less virus getting into the cell, he says.

A recent computer simulation study also found that several statins could inhibit SARS-CoV-2’s main protease—an enzyme essential for viral replication and transcription. The results, the authors write in the paper describing them, indicate that statins could “directly affect the virus particle,” though there hasn’t been a study in cells to show this yet. 

That effect is probably less important than statins’ role in fixing endothelial damage, says Fedson, who was not involved in the modeling study. “But we shouldn’t overlook it.”

Statins’ performance in clinical trials for infections

Although the data on COVID-19 and statins are scant, evidence from other infections, such as influenza, indicate that the drugs could have some benefit. For instance, individuals who were already taking a moderate dose of statins before coming down with the flu had a reduced risk of dying from the infection compared with those who did not take statins, and patients who took statins before or during a hospital visit for flu also appeared to have a lower risk of dying from the infection.

In addition to flu, statins have also been suggested as a treatment for Ebola. In a small study in Sierra Leone in 2014, approximately 100 individuals infected with the virus were treated with a combination of a statin called atorvastatin and an antihypertensive called irbesartan for five to six days. Some of the patients also received clomiphene, which was thought to have antiviral effects against Ebola, for two to three days. Data from the study weren’t released publicly, but individual health records, letters, and memoranda shared by clinicians who treated these patients showed that dozens of them survived the Ebola infection and were released from care. Typically, half of patients who are infected with Ebola die, according to the World Health Organization (WHO).

If we can prevent even a small number of patients getting to the stage of needing mechanical ventilation and dying, I think it will help.

—Haleema Shakur-Still, London School of Hygiene and Tropical Medicine

Together, statins and antihypertensives seemed to improve survival in the patients with Ebola, Fedson says. Still, even with these seemingly promising preliminary findings, the WHO chose not to set up any additional clinical trials or other studies to follow up on the results, he notes.

There have also been randomized clinical trials using statins to treat sepsis and ARDS. In three of those trials, patients were already mechanically ventilated by the time they received statins; the drugs did not appear to reduce mortality. A small trial using statins to treat patients hospitalized with sepsis showed more promise, as a large percentage of cases did not develop into severe sepsis with multi-organ failure. There weren’t enough study participants for the team to draw statistical significance from the findings.

The WHO has turned down requests from Fedson to include statins in trials to treat patients infected with SARS-CoV-2. Letters Fedson shared with The Scientist reveal the organization’s hesitancy to support the drug treatment because of the lack of evidence showing statins will be successful against COVID-19. The Gates Foundation has also turned down a request by John Costello of First Group Healthcare in France to start a trial in several Central African countries with a combination of statins and antihypertensive drugs called ARBs. The reason, according to a letter to Costello from the Gates Foundation, is because one trial on ARBs alone is already underway and because statins didn’t work for sepsis and ARDS in previous studies of mechanically ventilated patients.

See “Blood Pressure Meds Point the Way to Possible COVID-19 Treatment”

Kass says the use of statins to treat COVID-19 could go either way. “It could be that even though it’s a good thing it is not enough of a good thing to make a dent into COVID-19. It’s like putting on a rain jacket when it’s drizzling, you’re going to stay dry, but if you go out with the same rain jacket in a class four hurricane, you’re going to get soaked,” he explains. “So if COVID-19 is more like a class four hurricane for the blood vessels, then even though statins help to protect them, it may not be enough. That’s why we need to do the study.”

Shakur-Still and colleagues’ trial in Pakistan and Nigeria is a small step in that direction. But more could be done right now with statins to save lives, especially in less-developed countries, Fedson says.

Shakur-Still shares a similar sentiment. When thinking about her trial, she says, she can’t decide if she’s excited for it to start or terrified. “Speaking to colleagues in Islamabad, Pakistan, last weekend, there were no ICU beds for COVID-19 patients. This terrifies me,” she says. “However, if we can prevent even a small number of patients getting to the stage of needing mechanical ventilation and dying, I think it will help.”

Statin side-effects only felt by those who believe in them – study | Statins

Common side-effects of statins are not down to the drugs, but are instead a result of patients’ negative expectations, research suggests.

Statins are typically prescribed to help lower levels of “bad cholesterol” – or low-density lipoprotein – in order to reduce the risk of a heart attack or stroke. A recent report estimated that the drugs prevent around 80,000 such incidents a year in the UK.

Despite their benefits, statins have been caught up in a storm of controversy, with critics questioning the safety and efficacy of the drugs after NHS guidelines advised that prescriptions should be extended to those at lower risk of heart attack.

But the new study suggests common side-effects of muscle pain and weakness are not a result of the drugs themselves, but rather patients’ negative beliefs about the medication – a phenomenon known as the nocebo effect.

“You only get the muscle-related symptoms when you know you are taking the drug,” Peter Sever, lead author of the study from the national heart and lung institute at Imperial College London.

He added that it was important to note that patients are not imagining their pains. “Patients genuinely get the symptoms,” he said. “But you cannot attribute that, in this case, to the drug.”

The study echoes findings from other studies, including research published three years ago, which have also suggested the side-effects of statins are minimal, despite up to a fifth of patients reporting side-effects, chiefly muscle pain and weakness.

The researchers say they hope the latest research will finally quash the debate around statins, and reassure both doctors and patients that the benefits of the drugs outweigh concerns around side-effects. “Seldom in the history of modern therapeutics have the substantial proven benefits of a treatment been compromised to such an extent by serious misrepresentations of the evidence for its safety,” the authors write..

Indeed, research published this week in the journal BMJ Open suggests that more than six million at-risk people in the UK are either not taking statins or are not on a high enough dose.

“There are people out there who are dying because they are not taking statins and the numbers are huge – the numbers are tens of thousands if not hundreds of thousands, and they are dying because of a nocebo effect, in my opinion,” said Sever.

While statins do have some potentially serious side effects, including a slightly raised risk of developing type II diabetes and, very rarely, a potentially fatal muscle condition known as rhabdomyolysis, Sever said that the Medicines and Healthcare Products Regulatory Agency (MHRA) should remove warnings of side-effects including muscle pain and weakness, sleep disturbance, erectile dysfunction and problems with cognitive function.

“We would hope that the MHRA will withdraw that request that these side effects should be listed,” he said.

Sever also fiercely rebuked those those who claim that high cholesterol is not linked to a risk of heart disease and stroke. “It is just like the MMR [scandal] – it is a small number of people getting up with opinions that are based on bad science,” he said.

Liam Smeeth, professor of clinical epidemiology at the London School of Hygiene and Tropical Medicine, who was not involved in the research, welcomed the study, saying that it highlights the danger of messages exaggerating the side-effects of statins. “I do think the MHRA advice could be toned down,” he added.

An MHRA spokesperson said research has shown the benefits of statins, adding that medically significant side effects are rare.

“Our priority is to ensure that the benefits of medication outweigh the risks,” they said. “Any new significant information on the efficacy or safety of statins will be carefully reviewed and action will be taken if required, including updates to product labelling. ”

While the study and analyses received funding from Pfizer, the authors stress that the drugs company played no role in the research.

Writing in the Lancet, researchers from the UK and Sweden describe how they carried out research between 1998 and 2004. More than 10,000 at-risk patients – predominantly white, male and over 60 – were randomly allocated to one of two groups, either taking statins or a placebo, and followed for more than three years. Neither the participants nor their doctors knew which group they belonged to.

In the second part of the study, 9,899 of the patients had the medication or placebo stopped, and both groups were then given the option of taking statins. The patients were then followed for more than two years.

“The uniqueness about the study was that these were the same patients who were followed throughout, they were seen by the same doctors, the same teams, the same way of recording the side-effects,” said Sever.

The team found that, when neither the patient nor the doctors were aware of whether statins were being taken, those taking the drugs reported similar rates of muscle problems and erectile disfunction to those taking a placebo.

By contrast, when the patients and their doctors were aware of whether the patient was taking statins, reports of muscle-related problems were 41% higher among those who were taking statins.

The study also found that statins were linked to fewer sleep disturbances, but an increase in reports of needing to urinate at night and urinate more frequently, while there were too few reports of cognitive problems to draw any conclusions.

The results, say researchers, indicates that muscle-related problems linked to statins are largely the product of the “nocebo” effect.

“If patients now begin to understand that actually this is not something that is specifically due to the chemistry of the drug then it may well be that your muscle aches and pains might get better,” said Sever.

While the authors admit that the dose of statins used in the study is low compared to levels currently prescribed, they stress that other studies have found no link between dose and severity of side effects. However only one type of statin, atorvastatin, was fully considered in the latest study, and it is not known if similar results would be seen among those of different ethnicities.

Sir Nilesh Samani, medical director at the British Heart Foundation, said that the perception that statins cause significant side-effects, including muscle aches, memory loss, sleep disturbance and erectile dysfunction has clouded their use.

“However, these complaints are not uncommon in the general population for a whole variety of reasons,” he said. “Therefore when patients take a statin and develop such symptoms, these understandably attribute them to the statin when it may not be the cause. This study shows that this might indeed be the case.”

APO-Atorvastatin – NPS MedicineWise

What is in this leaflet

This leaflet answers some of the more common questions about APO-Atorvastatin. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits he/she expects it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine.
You may need to read it again.

What this medicine is used for

The name of your medicine is APO-Atorvastatin. It contains the active ingredient atorvastatin.

Atorvastatin is used to lower high cholesterol levels.

It is also used to help reduce the risk of having a heart attack or stroke in people who have high blood pressure and coronary heart disease (CHD). Examples of risk factors for CHD include diabetes, a history of stroke, or small blood vessel disease.

What is Cholesterol?

Everyone has cholesterol in their blood. It is a type of blood fat needed by the body for many things, such as building the cell lining, making bile acids (which help to digest food) and some hormones. However, too much cholesterol can be a problem.

Cholesterol is present in many foods and is also made in your body by the liver. If your body makes too much cholesterol or you have too much cholesterol in your diet, then your level becomes too high.

High cholesterol is more likely to occur with certain diseases or if you have a family history of high cholesterol.

There are different types of cholesterol. LDL, or low-density lipoprotein, is the ‘bad’ cholesterol that can block your blood vessels. HDL, or high density lipoprotein, cholesterol is the ‘good’ cholesterol that is thought to remove the bad cholesterol from the blood vessels.

When you have high levels of ‘bad’ cholesterol in your blood, it may begin to ‘stick’ to the inside of your blood vessels instead of being carried to the parts of the body where it is needed. Over time, this can form hard areas, also called plaque, on the walls of your blood vessels, making it more difficult for the blood to flow. Sometimes the plaque can detach from the vessel wall and float in the blood stream; it can then reach a smaller vessel and completely block it. This blocking of your blood vessels can lead to several types of blood vessel disease, heart attack, angina and stroke.

There is another type of blood fat called triglyceride, which is a source of energy. However, high levels of triglyceride can be associated with a low level of ‘good’ cholesterol and may increase your risk of heart disease.

In some patients, APO-Atorvastatin is used to treat high cholesterol and high triglycerides together.

In most people, there are no symptoms of abnormal cholesterol or triglyceride levels. Your doctor can measure your levels with a simple blood test.

How it works

APO-Atorvastatin belongs to a group of medicines called HMG-CoA reductase inhibitors. It works by reducing the amount of cholesterol made by the liver. This medicine reduces the ‘bad’ cholesterol and can raise the ‘good’ cholesterol. It also helps to protect you from a heart attack or stroke.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.
Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor’s prescription.

Before you take this medicine

When you must not take it

Do not take APO-Atorvastatin if you have an allergy to:

• any medicines containing atorvastatin
• any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin.

Do not take APO-Atorvastatin if you have active liver disease.

Do not take this medicine if you are pregnant or intend to become pregnant.

If you are a woman of childbearing age and are taking this medicine, use a proven method of birth control to avoid pregnancy.
The medicine may affect your developing baby if you take it during pregnancy.

Do not breast-feed if you are taking this medicine.
The active ingredient in this medicine may pass into breast milk and affect your baby.

Do not take this medicine if you are taking the antibiotic fusidic acid which is used to treat infections.

Do not take this medicine if you are taking the antivirals, glecaprevir/pibrentasvir for the treatment of Hepatitis C.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.
If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether to start taking APO-Atorvastatin, talk to your doctor.

Before you start to take it

Your doctor will ask you to have your liver function tested before you start to take this medicine

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

• liver problems
• kidney problems
• muscle pain, tenderness or weakness from other medicines used to treat high cholesterol or triglycerides
• a type of stroke called a haemorrhagic stroke or a type of stroke called a lacunar stroke. If you have had one of these strokes before, this medicine may increase the risk of you having a haemorrhagic stroke.
• breathing problems.

Tell your doctor if you drink alcohol regularly.

If you have not told your doctor about any of the above, tell him/ her before you start taking this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

• all prescription medicines
• all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines may be affected by APO-Atorvastatin. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor will advise you.

Tell your doctor or pharmacist if you are taking any of the following:

• digoxin, a medicine used to treat some heart problems
• diltiazem, a medicine used to treat angina
• other medicines to treat high cholesterol or triglycerides
• antacids, medicines used to treat reflux or ulcers
• the antibiotics erythromycin, clarithromycin, rifampicin or fusidic acid
• phenytoin, a medicine used to treat epilepsy (seizures)
• oral contraceptives for birth control
• ciclosporin, a medicine used to suppress the immune system
• some medicines used to treat some fungal infections, such as itraconazole or ketoconazole
• protease inhibitors for the treatment of HIV infection and/or Hepatitis C, such as efavirenz, fosamprenavir, ritonavir, boceprevir, telaprevir, tipranavir/ritonavir, elbasvir/grazoprevir and simeprevir
• HCV non-structural protein 5A (NS5A)/5B (NS5B) inhibitors
• letermovir
• spironolactone, a medicine used to treat high blood pressure and certain types of swelling
• vitamin B3
• colchicine, a medicine used to treat a disease with painful, swollen joints caused by uric acid crystals.

Your doctor and pharmacist have more information on medicines to be careful with or to avoid while taking this medicine.

How to take this medicine

Follow all directions given to you by your doctor and pharmacist carefully.
These directions may differ from the information contained in this leaflet.

Your doctor will discuss with you the need to be on a diet while you are taking APO-Atorvastatin.

Follow your agreed diet plant carefully.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to take

Your doctor will tell you how many tablets you need to take each day. This may depend on your condition and whether or not you are taking any other medicines.

The usual dose of APO-Atorvastatin is between 10 mg-80 mg taken once a day.

How to take it

Swallow the tablet(s) whole with a full glass of water. Do not chew or crush the tablets.

When to take it

APO-Atorvastatin can be taken at any time of the day. However, your dose of APO-Atorvastatin should be taken at about the same time each day.
Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

APO-Atorvastatin can be taken with or without food.

How long to take it

Take APO-Atorvastatin every day and continue taking it for as long as your doctor tells you.

APO-Atorvastatin helps to lower your levels of cholesterol, but it does not cure your condition. It is important to keep taking your medicine even if you feel well. If you stop taking APO-Atorvastatin, your cholesterol levels may rise again.

If you forget to take it

If it is less than 12 hours before your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed.
This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, talk to your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much of this medicine. Do this even if there are no signs of discomfort or poisoning.
You may need urgent medical attention.

While you are using this medicine

Things you must do

Keep all of your doctor’s appointments so that your progress can be checked.

Your doctor will ask you to have your liver function tested from time to time while you are taking APO-Atorvastatin to make sure the medicine is working and to prevent unwanted side effects.

Your cholesterol and triglyceride levels also need to be checked regularly while you are taking this medicine.

A regular blood test to check an enzyme called creatine kinase (CK) may be needed. CK in your blood can rise after muscle injury which can be caused by medicines used to treat cholesterol or triglycerides, such as APO-Atorvastatin.

If you become pregnant while you are taking APO-Atorvastatin, stop taking it and contact your doctor immediately.

If you are about to started on any new medicine, remind your doctor and pharmacist that you are taking APO-Atorvastatin.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

Things you must not do

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not take this medicine to treat any other complaints unless your doctor tells you to.

Things to be careful of

Avoid drinking large quantities of alcohol.
Drinking large quantities of alcohol while taking APO-Atorvastatin may increase your chance of getting liver problems.

Avoid drinking large quantities of grapefruit juice.
Grapefruit juice contains one or more components that alter the metabolism of some medicines, including APO-Atorvastatin.

Drinking very large quantities (over 1.2 litres) of grapefruit juice each day while taking APO-Atorvastatin increases your chance of getting side effects.

Be careful driving or operating machinery until you know how APO-Atorvastatin affects you.
APO-Atorvastatin generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, APO-Atorvastatin may cause dizziness in some people.

If you feel dizzy, do not drive, operate machinery or do anything else that could be dangerous.

Things that would be helpful for your condition

Some self-help measures suggested below may assist your condition. Your doctor or pharmacist can give your more information about these measures:

• Weight: While you are taking APO-Atorvastatin, you need to follow a diet plan agreed with your doctor. This may include measures to lose some weight.
• Exercise: regular exercise can help lower cholesterol levels. It is important not to overdo it. Before commencing exercise, you should consult your doctor who will suggest the most suitable exercise for you. If you experience any discomfort when exercising, see your doctor.
• Alcohol: Excessive alcohol intake can raise your cholesterol levels or affect your liver function, which could increase the chance of getting unwanted side effects. Your doctor may discuss with you whether you should reduce the amount of alcohol you drink.
• Smoking: Smoking increases the risk of you suffering from heart problems. Your doctor may advise you to stop smoking.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking APO-Atorvastatin.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the list of possible side effects.
You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

• muscle and joint pain, muscle weakness, especially in the forearms, thighs, hips, shoulders, neck and back
• difficulty climbing stairs or standing up from a chair
• difficulty lifting arms over the head
• falling, and difficulty getting up from a fall
• constipation, diarrhoea
• stomach or belly pain, nausea (feeling sick)
• heartburn, indigestion or wind
• urine infection
• headache
• stuffy or runny nose
• nose bleeds
• rash

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

• yellowing of the skin and eyes and dark coloured urine
• feeling weak and tired, excessively thirsty and passing more urine
• problems with breathing including shortness of breath, persistent cough and fever.

These are serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, stop taking your medicine and tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

• symptoms of allergy such as skin rash, itching, swelling of the face, lips, mouth tongue, throat or neck which may cause difficulty in swallowing or breathing
• chest pain
• unexpected muscle pain, tenderness or weakness not caused by exercise, particularly if you also feel unwell or have a fever
• sudden severe headache which may be accompanied by nausea, vomiting, loss of sensation, tingling in any part of the body or ringing in the ears
• severe blisters and bleeding of the lips, eyes, mouth, nose or genitals.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor if you notice anything else that is making you feel unwell.
Other side effects not listed above may also occur in some people.

Storage and Disposal

Storage

Keep your tablets in the pack until it is time to take them.
If you take the tablets out of the original packaging they may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25°C.

Protect from light.

Do not store this medicine or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.
Heat and dampness can destroy some medicines.

Keep it where children cannot reach it.
A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

APO-Atorvastatin 10 mg tablets are white to off-white, elliptical, film-coated tablets debossed “AS10” on one side and plain on the other side. AUST R 286636, 179854.

APO-Atorvastatin 20 mg tablets are white to off-white, elliptical, film-coated tablets debossed “AS20” on one side and plain on the other side. AUST R 286637, 179822.

APO-Atorvastatin 40 mg tablets are white to off-white, elliptical, film-coated tablets debossed “AS40” on one side and plain on the other side. AUST R 286638, 179857.

APO-Atorvastatin 80 mg tablets are white to off-white, elliptical, film-coated tablets debossed “AS80” on one side and plain on the other side. AUST R 286639, 179852.

They are available in blister packs of 30 tablets and bottles of 100s.

Ingredients

The active ingredient of APO-Atorvastatin is atorvastatin (as calcium trihydrate).

This medicine also contains the following:

• calcium carbonate
• croscarmellose sodium
• lactose monohydrate
• microcrystalline cellulose
• magnesium stearate
• Polysorbate 80
• Opadry YS-1-7040 White (PI 2695)
• hyprolose
• Antifoam emulsion Q7-2587 (PI 1515)
• Candelilla Wax (only for 10 mg, 20 mg and 40 mg tablets)

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113
Australia
Tel: (02) 8877 8333
Web: www1.apotex.com/au

APO is a registered trademark of Apotex Inc.

This leaflet was prepared in March 2021.

Published by MIMS May 2021

Do Statins Increase or Decrease Alzheimer’s Risk?

Learn why statins may both increase and decrease the risk of dementia symptoms.

After late-onset Alzheimer’s disease (AD) was diagnosed in his father, Martin* took greater care of his own health. At age 63, he wanted to do everything he could to improve his chances of avoiding AD. At his father’s appointment, he asked about something that was bothering him: “My primary care doc says my cholesterol has been too high and that I should take a statin. I know that’s supposed to lower my cholesterol and my primary care physician says it will reduce my dementia risk, but I’ve also read that statins can interfere with memory…what should I do? Do statins increase or decrease AD risk?”

* The name and details were changed to protect privacy.

Is it possible for a medication both to increase and to decrease dementia risk? In the case of statins, this can appear to be true. Overall, the beneficial effects of statins seem to outweigh their small risk of interfering with cognitive functioning, but we can’t ignore the many reports of memory impairment associated with these medications. How can this be? There is evidence both for statin-associated brain protection and for statin-associated cognitive interference…and there is a credible explanation.

Evidence for Statins Decreasing Risk of Dementia

Statins are among the most frequently prescribed medications in the United States. Nearly one in three US adults age 40 and older is prescribed a statin. The benefits linked with these medications are very important in fighting cardiovascular disease, which remains our leading cause of death. Statins lower low-density lipoprotein cholesterol and triglycerides. They increase high density lipoprotein cholesterol, also known as the “good” cholesterol. Statins have been convincingly shown to reduce the risk of atherosclerotic heart disease and ischemic stroke.¹

In addition to their cardiovascular benefits, statins appear modestly to reduce the risk for developing Alzheimer’s dementia. Evidence for this effect is not consistent. Some large studies find no benefit, while others demonstrate an effect important enough to grab our attention. The most recent carefully designed review and analysis conclude that AD risk is diminished with statin use, attributing the earlier disagreements to differing approaches that researchers took in gathering and understanding their results.² In addition, a recent large high-quality prospective study supported the benefits of statins for reducing AD risk and this study deserves our notice because it was a well-controlled, randomized investigation that evaluated dementia and statin use among over 3,000 older adults every two years for an average of 6.1 years. The researchers concluded that statin use was protective against AD in those adults under 65, though it appeared slightly to increase AD risk in adults over 80 years old.³

That’s great news, but what about the reports of cognitive problems linked with statin use?

Evidence for Statins Increasing Risk of Dementia

Alarming case reports began to accumulate in the early 2000’s. A description of 60 case reports, published in 2003, advised taking concerns about statin-related cognitive impairment seriously, though cognitive adverse responses were most likely uncommon.⁴ Simvastatin, atorvastatin, and pravastatin were the medications taken by the patients who were described. About half of these patients noticed cognitive problems within two months of starting treatment. The symptoms improved after drug discontinuation in about half of those affected, which is different from what would be expected of a person with Alzheimer’s disease, which is a progressive condition.

The link between cognitive symptoms and statins, furthermore, is supported by a couple of additional lines of evidence: first, some patients with this problem who noted improvement after stopping their statin medication experienced a recurrence when the medication was restarted.⁴ Second, a couple of small but well-designed experimental double-blind, placebo-controlled trials associated poorer performance on neuropsychological tests with the use of statins.^5,6 In a description of statin effects on a couple of affected patients, the authors reminded us that a cognitive effect which looks small on neuropsychological testing can cast a much larger shadow over actual day-to-day functioning.⁷

How Can Statins Both Increase and Decrease Risk?

A group of researchers from Denver have recently tried to explain how statins could be both helpful and harmful.¹ They note that statins, like other medications that affect metabolism in complex ways, act through more than one mechanism. Statins decrease cholesterol, and that may be an important reason for their cardiovascular benefits. Statin use reduces stroke risk and their cerebrovascular benefits may be important in reducing dementia. There may be additional effects beyond cholesterol reduction as well. Studies have suggested that atorvastatin, for example, can reduce β-amyloid production, reduce vascular inflammation, protect endothelial cell function and reduce brain ischemia.

But cholesterol is also an important structural component of the brain, enhancing brain function in multiple ways. Among other positive actions, cholesterol supports myelin sheath formation which protects brain cells and improves their functioning, supports mitochondrial function and promotes synaptic activity. Too great a reduction of brain cholesterol with statins that  enter the central nervous system might deprive the brain of cholesterol’s beneficial effects. Given this possibility, it makes sense that the cognitive problems associated with statins may be more likely to develop in people whose brains are exposed to a higher statin level. This can result from taking a higher statin dose or having less efficient metabolism of the medication. Some researchers suggest that the statins that more easily enter the brain because of their greater fat-solubility (lipophilicity) are more likely to affect cognitive functioning. Atorvastatin and simvastatin are lipophilic statins.¹

Martin’s father’s diagnosis encouraged him to pay more attention to his own healthy aging. He increased his exercise, improved his diet and weight, attempted to reduce the stress in his life, and made sure to get adequate sleep. His cholesterol remained higher than recommended and so he accepted the recommendation to take a low dose of statin medication. His cholesterol level dropped, with no obvious cognitive problems. He was reassured to know that the general benefits of statin medication for him were most likely larger than the risk of cognitive problems and that the medication was not expected to increase his risk for developing Alzheimer’s disease.

Resources:

Citations:

1. Schultz BG, Patten DK, Berlau DJ. The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms. Translational Neurodegeneration 2018. https://doi.org/10.1186/s40035-018-0110-3
2. Hersi M, Irvine B, Gupa P, et al. Risk factors associated with the onset and progression of Alzheimer’s disease: A systematic review of the evidence. NeuroToxicology 2017;61:143-187.
3. Li G, Shofer JB, Rhew IC, et al. Age-varying association between statin use and incident Alzheimer’s disease. J Am Geriatr Soc 2010; 58 (7):1311-7.
4. Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: Analysis of 60 case reports and review of the literature. Pharmacotherapy 2003;23(7):871-880.
5. Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. Am J Med 2000;108:538-46.
6. Muldoon MF, Ryan CM, Sereika SM, et al. Randomized trial of the effects of simvastatin in cognitive functioning in hypercholesterolemic adults. Am J Med 2004;117:823-9.
7. Suraweera C, de Silva V, Hanwella R. Simvastatin-induced cognitive dysfunction: two case reports. J Med Case Rep 2016;10: 83. Published online 2016 Apr 5. doi: 10.1186/s13256-016-0877-8

This content was last updated on: November 10, 2020

Statins and vitamin D – an unusual relationship | CATIE

Cholesterol-lowering medications, commonly called statins, are often prescribed by physicians for HIV-positive people. In general, when used correctly and in the right population, statins are generally safe, though they can sometimes affect the concentration of other medicines. In a minority of people who take statins, problems such as muscle weakness and pain can develop. Statins also have anti-inflammatory activity, which may aid in the ability of these drugs to help prevent heart attacks.

Observational studies have found associations between low levels of vitamin D in the blood and an increased risk for cardiovascular complications, including peripheral artery disease and heart attacks. However, because of built-in limitations, observational studies cannot prove that low levels of vitamin D are the cause of peripheral artery disease, heart attacks and other related complications. Still, some scientists remain intrigued by the potential of vitamin D in the area of cardiovascular health, perhaps for at least the following reasons:

• Cells lining blood vessels contain receptors for vitamin D. Exposure to this vitamin helps restrict the thickening of this lining. Such thickening would otherwise impede the flow of blood.
• Lab experiments have found that vitamin D can help reduce inflammation. Separate studies suggest that inflammation plays a role in accelerating cardiovascular disease.
• Vitamin D can very modestly help reduce blood pressure.

Researchers in several countries have conducted experiments with statins to assess their impact on vitamin D in HIV-negative people. Their findings suggest the following:

• Rosuvastatin (Crestor) can raise vitamin D levels about threefold in the blood.
• Atorvastatin (Lipitor) can have a similar effect on vitamin D as rosuvastatin.
• Other statins, such as lovastatin (Mevacor) and simvastatin (Zocor), can also increase the concentration of vitamin D in the blood.
• In contrast to the statins listed above, fluvastatin (Lescol) does not appear to raise vitamin D levels.

Small studies have found that vitamin D₃ supplements at a dose of 800 IU/day can lower levels of atorvastatin (by about 10%) and the chemicals into which it is broken down inside the body. Yet, despite these reduced levels of atorvastatin, the combination of vitamin D and atorvastatin appeared to have increased cholesterol-lowering activity more than either substance did alone.

In general, these studies exploring the impact of statins on vitamin D were small. Larger robust clinical trials will be needed to understand the complex ways in which statins and vitamin D might affect each other’s properties and actions.

—Sean R. Hosein

REFERENCES:

1. Giannarelli C, Klein RS, Badimon JJ. Cardiovascular implications of HIV-induced dyslipidemia. Atherosclerosis. 2011 Jun 13. [Epub ahead of print]
2. Grimes DS. Are statins analogues of vitamin D? Lancet. 2006 Jul 1;368(9529):83-6.
3. Gupta A, Thompson PD. The relationship of vitamin D deficiency to statin myopathy. Atherosclerosis. 2011 Mar;215(1):23-9.
4. Sathyapalan T, Shepherd J, Arnett C, et al. Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome. Clinical Chemistry. 2010 Nov;56(11):1696-700.
5. Ertugrul DT, Yavuz B, Cil H, et al. STATIN-D Study: Comparison of the influences of Rosuvastatin and Fluvastatin treatment on the levels of 25 Hydroxyvitamin D. Cardiovascular Therapeutics. 2011Apr;29(2):146-152.
6. Yavuz B, Ertugrul DT, Cil H, et al. Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovascular Drugs and Therapy. 2009 Aug;23(4):295-9.
7. Pérez-Castrillón JL, Vega G, Abad L, et al. Effects of atorvastatin on vitamin D levels in patients wit acute ischemic heart disease. American Journal of Cardiology. 2007 Apr 1;99(7):903-5.
8. Pérez-Castrillón JL, Abad L, Vega G, et al. Effect of atorvastatin on bone mineral density in patients with acute coronary syndrome. European Review for Medical and Pharmacological Sciences. 2008 Mar-Apr;12(2):83-8.

90,000 Early high-dose therapy with atorvastatin after myocardial infarction with ST segment elevation

The article was published in the journal “Health of Ukraine” Today 2018.

Stattya is supervised and displaced by the fast-paced viglyad. Translated from English. Larisa Strilchuk

Read Ukrainian article >>

Recently published studies, including IMPROVE-IT, have confirmed that lowering low-density lipoprotein cholesterol (LDL-C) levels below the currently recommended target values ​​has a protective effect against cardiovascular events, but does not reduce mortality.Given the cardiovascular and all-cause mortality rates recorded in large clinical trials that investigated primary and secondary prevention, statin therapy remains the cornerstone of lipid-lowering interventions.

In patients with acute coronary syndrome (ACS), statins have clearly been shown to be effective in reducing the risk of cardiovascular events in both the acute and chronic phases of coronary artery disease. It is known that the effects of statins depend not only on the duration of the appointment (the earlier, the better), but also on the intensity of use.Data from the ARMYDA-ACS study and several other studies have suggested that statins may reduce mechanical damage to the artery wall due to percutaneous coronary intervention (PCI). Moreover, the benefits of statins identified in these studies have led to the hypothesis of the role of these drugs in reducing inflammation, reducing oxidative stress and endothelial dysfunction; Thus, statin therapy can help stabilize atherosclerotic plaque not only by lowering the level of LDL cholesterol.

Among patients with ACS, higher levels of inflammation are observed in the case of ST-segment elevation myocardial infarction (STEMI). In addition, primary PCI and stenting due to mechanical damage provoke the instability of atherosclerotic plaques in the coronary bed; therefore, the results of revascularization are influenced by side effects, for example, the phenomenon of unrecovered blood flow (no-reflow), in the occurrence of which endothelial dysfunction plays a central role. Despite the importance of these aspects, there is little information in the published literature regarding the role of statins specifically in patients with STEMI.A recent trial has shown that high-dose atorvastatin prior to primary PCI in patients with STEMI can improve coronary blood flow below the site of thrombosis. Other small pilot studies have demonstrated that intensive statin therapy during the acute phase of STEMI reduced oxidized LDL (alLDL) levels, markers of inflammation, and inflammatory cytokines; reduced platelet activation ex vivo after a few hours and improved recovery of myocardial function 6 months after the event.

In the present study, in STEMI patients undergoing primary PCI, in the short term (after 1 month), the effect of early administration of high-dose therapy with atorvastatin (80 mg) and a medium dose of the same substance (20 mg) on ​​endothelial function, markers of vascular inflammation and stability of atherosclerotic plaques. The purpose of this trial was to investigate the dose dependence of these effects.

Materials and Methods

Atorvastatin was prescribed within 24 hours after the first contact with the doctor.Blood analysis and assessment of endothelial function using the EndoPat 2000 device (Israel) were carried out at randomization and after 1 month. Participants in both groups received optimal pharmacotherapy in accordance with the recommendations of the European Society of Cardiology. The primary endpoints of the study included changes in endothelium-dependent vasodilation after 30 days of treatment (according to the index of reactive hyperemia – IRG), as well as changes in the levels of highly sensitive C-reactive protein (hsCRP), interleukin (IL) 6, tumor necrosis factor (TNF) and LDL in plasma blood.Data processing was carried out using the methods of parametric and nonparametric statistics. Results were presented as mean ± standard deviation.

Results

A total of 52 patients were enrolled in the study and were randomized to receive atorvastatin 80 mg (n = 26) and 20 mg (n = 26). The average age of those included was 58.4 ± 11 years; 88.4% of the participants were male. The main characteristics did not differ between treatment groups, including no differences between STEMI localization: the anterior descending branch of the left coronary artery was involved in 46.2% of participants in the 80 mg group and in 45.7% of patients in the 20 mg group.A more pronounced decrease in total cholesterol level took place in the intensive statin therapy group: by 76 ± 19 mg / dL (38%) versus 61 ± 26 mg / dL (27%) in the 20 mg atorvastatin group (p = 0.001). Also, in the atorvastatin 80 mg group, the concentration of LDL cholesterol decreased more significantly: 72 ± 14 mg / dL (55%) versus 55 ± 28 mg / dL (37%) in the 20 mg group (p = 0.001). The level of HDL cholesterol increased in both groups without a significant difference between them. As for the content of triglycerides, a more significant decrease was recorded in the atorvastatin 80 mg group, however, the difference in indicators between the groups did not reach the level of statistical significance.

Baseline levels of hsCRP, IL-6 and TNF in blood plasma did not differ significantly. After 30 days of treatment, the hsCRP indicator significantly decreased in all study participants; the difference between baseline and endpoint was higher in the intensive statin therapy group (0.04 ± 0.02 versus 0.36 ± 0.3 mg / dL; p = 0.001). A similar trend was noted for IL-6: the endpoints were 1.12 ± 0.93 pg / ml in the 80 mg atorvastatin group versus 3.13 ± 2.84 pg / ml in the 20 mg group (p = 0.001).For TNF and dLDL, a significant decrease was recorded only in the atorvastatin 80 mg group. The mean IRG values ​​at the beginning of the study were the same in both groups. After 30 days of statin therapy in the general population of the study, the IRH increased from 1.55 ± 0.31 to 1.83 ± 0.21 (p = 0.0001).

Discussion

This study evaluated the short-term effects of early high-dose atorvastatin versus medium-dose therapy in STEMI patients undergoing PCI.At randomization, 53.8% of the participants had endothelial dysfunction. After 1 month, an improvement in this parameter was noted in the entire study population, as expected after ACS and stenting, however, in the intensive statin therapy group, the best IRH indices were achieved. Endothelial function provides cardiovascular homeostasis in both primary and secondary prevention. A number of studies have established a relationship between endothelial function, as determined by non-invasive methods, and the frequency of cardiovascular events.In addition, it was confirmed that vascular inflammation plays an important role in the development of atherosclerosis and its complications, in particular ACS. Plasma markers of systemic inflammation (hsCRP, IL-6, TNF) are predictors of cardiovascular events, as well as increased overall and cardiovascular mortality. Previous clinical studies have demonstrated the effectiveness of statin therapy in reducing inflammation after ACS. In this study, both doses of atorvastatin reduced the level of inflammatory biomarkers, but the effect was more pronounced in the intensive statin group.
In coronary events, systemic inflammation and endothelial dysfunction are closely related and together form a high risk associated with a significant likelihood of re-rupture of atherosclerotic plaque. Statins, especially hydrophobic molecules (atorvastatin), reduce the level of pro-inflammatory cytokines, which is accompanied by a decrease in the synthesis and release of CRP. The vascular effects of statins are especially important in patients with STEMI. This study and previous work confirm the need to reduce LDL-C levels to target values ​​and below in patients with acute coronary events in the period after hospital discharge.

Conclusions

In this study, atorvastatin demonstrated dose-dependent positive effects: during therapy with this drug, a decrease in hsCRP, IL-6 and TNF levels, as well as an improvement in endothelial function, were noted. This may be due to an improvement in the lipid profile and a direct effect on blood vessels, which were more pronounced with earlier administration of higher doses of the drug. These findings support the key role of target achievement in patients with acute coronary events.

Atorvastatin-LF (Belarus) | JLLC “Lekpharm”

Use with caution in patients with alcohol abuse and / or suffering from liver disease (history).

Effect on liver function

As with the use of other lipid-lowering agents of the same class, during treatment with the drug, a moderate (more than 3 times compared to the upper limit of the norm) increase in the serum activity of hepatic transaminases may appear.

Before starting, 6 weeks and 12 weeks after starting the drug or after increasing the dose, as well as during the entire course of treatment, it is necessary to monitor liver function indicators. Liver function should also be investigated when clinical signs of liver damage appear. In case of an increase in the level of hepatic transaminases, their activity should be monitored until it returns to normal. If the increase in the activity of aspartic transaminase (AST) or alanine transaminase (ALT) more than 3 times compared with the upper limit of the norm persists, it is recommended to reduce the dose or discontinue the drug.

Lipromac-LF should be used with caution in patients who consume significant amounts of alcohol and / or have a history of liver disease.

Aggressive cholesterol-lowering therapy for the prevention of stroke

In the course of the conducted studies, it was found that among patients with coronary heart disease who had recently suffered a stroke or transient ischemic attack, hemorrhagic stroke was observed more often in patients receiving 80 mg of atorvastatin than in patients receiving placebo.In particular, an increased risk was observed in patients who had already had a hemorrhagic stroke or lacunar infarction at the time of study initiation. With regard to patients with previous hemorrhagic stroke or lacunar infarction, the balance of the risk / benefit ratio of a dose of atorvastatin 80 mg is not clear; the possible risk of hemorrhagic stroke should be carefully evaluated before starting therapy.

Effect on skeletal muscle

In the treatment of atorvastatin, as in the use of similar drugs of this group, cases of rhabdomyolysis were rarely observed, which were accompanied by acute renal failure resulting from myoglobinuria.A history of renal failure may be a risk factor for the development of rhabdomyolysis. In such patients, more careful monitoring of skeletal muscle function is necessary.

Treatment with atorvastatin, like other statins, can cause myopathy, which is manifested by pain and weakness in the muscles in combination with an increase in creatine phosphokinase (CPK) activity by more than 10 times compared to the upper limit of the norm. Concomitant use of high doses of atorvastatin and certain drugs such as cyclosporine and strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, and HIV protease inhibitors) increases the risk of myopathy / rhabdomyolysis.

There are rare reports of the development of immune necrotizing myopathy, autoimmune myopathy associated with the intake of statins. Immune necrotizing myopathy is characterized by proximal muscle weakness and increased creatine kinase levels, which persist even after discontinuation of statin therapy; muscle biopsy reveals necrotizing myopathy without significant inflammation; improvement occurs when taking immunosuppressive drugs.

Myopathy should be suspected in any patient with diffuse myalgia, muscle soreness or weakness, and / or a marked increase in CPK activity.Patients should be warned that they should immediately inform their doctor about the appearance of unexplained muscle pain or weakness, unless accompanied by malaise or fever. Therapy with atorvastatin should be discontinued in the event of a pronounced increase in CPK activity or in the presence of confirmed or suspected myopathy.

The risk of myopathy in the treatment of other drugs of this class increased with the concomitant use of cyclosporine, fibrates, erythromycin, clarithromycin, hepatitis C protease inhibitor telaprevir, a combination of HIV protease inhibitors, including saquinavir and ritonavir, lopinavir and ritonavir, tipranaviravir, and fistonavir fosamprenavir and ritonavir, niacin, or azole antifungals.Prescribing atorvastatin in combination with fibrates, erythromycin, clarithromycin, a combination of saquinavir and ritonavir, lopinavir and ritonavir, darunavir and ritonavir, fosamprenavir, fosamprenavir and ritonavir, azole antifungals and lipidosinic acid should be carefully dosed and treated with nicotinic acid. monitor patients regularly for any signs or symptoms of muscle pain or weakness, especially during the first months of treatment and when the dose of any drug is increased.Low initial and maintenance doses of atorvastatin should be prescribed when taken concomitantly with these drugs. In such situations, periodic determination of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.

Recommendations for the prescription of interacting medicinal products are given in the table (see the section “Interaction with other medicinal products”).

Cases of myopathy, including rhabdomyolysis, have been reported when atorvastatin is coadministered with colchicine, so caution must be exercised in this case.Patients should be warned to see a doctor immediately if they develop unexplained muscle pain or weakness, especially if accompanied by malaise or fever.

Before starting therapy

Atorvastatin should be used with caution in patients with a predisposition to rhabdomyolysis. The CPK level should be determined before starting therapy in the following cases:

90 095 90 096 renal failure;

90,096 hypothyroidism;

90,096 individual or family history of hereditary muscle diseases;

90,096 prior muscle toxicity due to statin or fibrate use;

90,096 previous liver disease and / or alcohol abuse;

90,096 elderly patients (over 70 years old) – the need for laboratory data in this case is also caused by the presence of other factors of predisposition to rhabdomyolysis;

90,096 cases of increased plasma concentration (for example, cases of interaction and use in special populations, including genetic subpopulations).

In the cases listed above, the ratio between risk and potential benefit should be assessed, clinical observation is recommended.

With a significant increase in the concentration of CPK (exceeding the upper limit of the norm by more than 5 times) at the initial level, treatment should not be started.

Measurement of CPK levels

You should not measure the CPK level after heavy physical exertion or in the presence of other factors responsible for the increase in the CPK level, as this will complicate the interpretation of the test results.If the initial CPK levels are markedly increased (more than 5 times compared to the upper limit of the norm), it is necessary to re-analyze the results in 5-7 days to confirm the results.

Endocrine function

Increases in HbAlc and fasting serum glucose have been reported with HMG-CoA reductase inhibitors, including atorvastatin. Statins affect cholesterol synthesis, and theoretically can inhibit the production of adrenal cortex hormones and / or sex steroid hormones.Clinical studies have shown that atorvastatin does not decrease the basal plasma cortisol concentration and does not adversely affect adrenal reserve. The effect of statins on male fertility has not been studied in a sufficient number of patients. The effects, if any, on the pituitary-gonadal system in premenopausal women are unknown. Care must be taken when prescribing statins with drugs that can lower the level or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine.

Interstitial lung diseases

There have been reports of very rare cases of the development of interstitial lung disease when taking statins, especially with long-term therapy. If symptoms of interstitial lung disease appear, such as respiratory distress, shortness of breath, unproductive cough, worsening of the general condition (fatigue, weight loss, fever), statin therapy should be discontinued.

Diabetes mellitus

Some evidence suggests that statins, as a class, raise blood glucose levels and, in patients at high risk of developing diabetes, may cause high blood sugar levels that require appropriate treatment.However, the benefit of statins in reducing the risk of cardiovascular disease outweighs the small increase in the risk of diabetes, so statins should not be discontinued. There are grounds for periodic monitoring of glycemia in patients, especially those at risk (fasting glucose 5.6 – 6.9 mmol / L, body mass index> 30 kg / m2, increased triglyceride levels or hypertension) taking statins.

Doctors RF

Pharmacological action – lipid-lowering.

Inside, at any time of the day, regardless of food intake.

Before starting treatment with Atorvastatin, you should try to control hypercholesterolemia with diet, exercise and weight loss in obese patients, as well as therapy for the underlying disease.

When prescribing the drug, the patient must be recommended a standard cholesterol-lowering diet, which he must adhere to during the entire period of therapy.

The dose of the drug varies from 10 to 80 mg 1 time per day and is titrated taking into account the concentration of LDL-C, the goal of therapy and the individual response to the therapy. The maximum daily dose of the drug is 80 mg.

At the beginning of treatment and / or during an increase in the dose of Atorvastatin, it is necessary to monitor the concentration of blood plasma lipids every 2–4 weeks and adjust the dose of the drug accordingly.

Homozygous familial hypercholesterolemia. In most cases, 80 mg is prescribed 1 time per day (decrease in the concentration of LDL-C by 18–45%).

Heterozygous familial hypercholesterolemia. The initial dose is 10 mg / day (to ensure the indicated dosage regimen, atorvastatin preparations should be used at a dosage of 10 mg). The dose should be selected individually and the relevance of the dose should be assessed every 4 weeks with a possible increase to 40 mg / day. Then the dose can be either increased to the maximum (80 mg / day), or it is possible to combine bile acid sequestrants with atorvastatin at a dose of 40 mg / day.

Prevention of cardiovascular diseases. In primary prevention studies, the dose of atorvastatin was 10 mg / day (to ensure the indicated dosage regimen, atorvastatin preparations should be used at a dosage of 10 mg). It may be necessary to increase the dose in order to achieve the values ​​of Xc-LDL, corresponding to current recommendations.

The dose of the drug must be titrated depending on the goal of lipid-lowering therapy. Dose adjustments should be made every 4 weeks or more.

Special patient groups

Lack of liver function. In case of insufficiency of liver function, the dose of Atorvastatin should be reduced, with regular monitoring of the activity of hepatic transaminases: AST and ALT.

Lack of renal function. Impairment of renal function does not affect the concentration of atorvastatin in the blood plasma or the degree of decrease in the concentration of LDL-C, therefore, no dose adjustment is required.

Elderly patients. No differences were found in the therapeutic efficacy and safety of the drug Atorvastatin in elderly patients compared to the general population; dose adjustment is not required.

Use in combination with other drugs. If concomitant use with cyclosporine, telaprevir or tipranavir / ritonavir is required, atorvastatin 10 mg should be used.

Care should be taken to use the lowest effective dose of atorvastatin when used with HIV protease inhibitors, hepatitis C protease inhibitors (boceprevir), clarithromycin and itraconazole.

Tablets, film-coated, 40 mg and 80 mg. In a blister strip made of PVC film and lacquered aluminum foil, 10 pcs. 1, 2, 3, 4 or 5 blisters in a cardboard box.

ALSI Pharma JSC.

Claims should be sent to the address: 129272, Russia, Moscow, Trifonovskiy Tup., 3.

Tel .: (495) 787-70-55.

Address of the place of production: 610044, Russia, Kirov region, Kirov, st. Luhansk, 53 century.

In a dry, dark place at a temperature not exceeding 25 ° C.

3 years.

Do not use after the expiry date stated on the package.

90,000 7 common myths about atorvastatin

Atorvastatin, one of the 10 most commonly prescribed drugs, is excellent in lowering cholesterol but often gets a bad rap. Muscle aches and cramps, diarrhea and indigestion are side effects of atorvastatin. And they certainly deserve attention.

A large study found that about 50% of patients taking a cholesterol-lowering drug quit it, and one of the main reasons is side effects. But over 60% of patients who stop taking statins later resume treatment, and almost all then remain on statins for a long time.

What is the reason for this? This likely means that most of the side effects people get are not directly caused by a statin or become more manageable over time.

Common myths about the side effects of atorvastatin.

1) Atorvastatin causes cancer

No. There is no conclusive evidence that atorvastatin or any other statin increases the risk of cancer. Research over the past few years has shown a protective effect of statins against breast, pancreatic and lung cancer in some patients. A recent large meta-analysis also showed that statins can reduce the risk of cancer in people with type 2 diabetes.

2) Atorvastatin is harmful to the liver

Very rarely (in 0.5-3% of cases), statins can cause an increase in blood counts in the liver, which in the past was of great concern to doctors. If this occurs, it is usually in the first 3 months of treatment and is seen in people taking higher doses of statins. But research has also shown that people on statins actually have the same level of liver damage as people not on statins.

3) Atorvastatin causes joint pain or arthritis

Statins can cause muscle pain or myalgia in 7% of people taking them.But even though they shouldn’t cause joint pain, research shows that some statin users are more prone to joint pain. It is not known exactly why this is the case, and there is no research to this effect. But one theory is that joint pain is more common in older people who also take more statins.
One thing is for sure: if new pains develop in the hips, knees, shoulders and small joints of the arms and legs, it is worth talking to your doctor about it.Statin is unlikely to be the cause.

4) Atorvastatin causes depression

Some people have expressed concern about depression and an increased risk of suicide with atorvastatin, but this is not the case. Atorvastatin is not associated with an increased risk of suicide or depression.

5) Atorvastatin induces drowsiness

While some medications can cause fatigue, statins such as atorvastatin should not cause drowsiness.

6) Atorvastatin causes headache

Headache is one of the most common reasons a person visits their health care provider, but headaches do not appear to be associated with atorvastatin use. Atorvastatin should not worsen or cause headache.

7) Atorvastatin causes erectile dysfunction

No, but in fact it may be vice versa.