Effect On Statins On Lipid And Lipoprotein Levels
The major effect of statins is lowering LDL-C levels. The effect of the various statins at different doses on LDL-C levels is shown in . As can be seen in different statins have varying abilities to lower LDL-C with maximal reductions of approximately 60% seen with rosuvastatin 40mg. Doubling the dose of a statin results in an approximate 6% further decrease in LDL-C levels. The percent reduction in LDL-C levels is similar in patients with high and low starting LDL-C levels but the absolute decrease is greater if the starting LDL-C is high. Because of this profound ability of statins to lower LDL-C levels, treatment with these drugs as monotherapy is often sufficient to lower LDL-C below target levels.
Effect Of Pcsk9 Inhibitors On Clinical Outcomes
FOURIER TRIAL
It should be noted that that the duration of the FOURIER trial was very short and it is well recognized from previous statin trials that the beneficial effects of lowering LDL-C levels takes time with only modest effects observed during the first year of treatment. In the FOURIER trial the reduction of cardiovascular death, myocardial infarction, or stroke was 16% during the first year but was 25% beyond 12 months. Thus, long-term benefit may be greater than observed during the study.
ODYSSEY TRIAL
SUMMARY OF OUTCOME TRIALS
It should be noted that that the duration of the PCSK9 outcome trials were relatively short and it is well recognized from previous statin trials that the beneficial effects of lowering LDL-C levels takes time with only modest effects observed during the first year of treatment. In the FOURIER trial the reduction of cardiovascular death, myocardial infarction, or stroke was 16% during the first year but was 25% beyond 12 months. In the ODYSSEY trial the occurrence of cardiovascular events was similar in the alirocumab and placebo group during the first year of the study with benefits of alirocumab appearing after year one. Thus, the long-term benefits of treatment with a PCSK9 inhibitor may be greater than that observed during these relatively short-term studies.
GLAGOV TRIAL
VENOUS THROMBOEMBOLISM
What Do Statins Do
Your body actually needs some cholesterol to function well. Your body gets cholesterol by eating certain foods and by making it in your liver. However, dangers arise when your cholesterol levels get too high. Statins work to decrease cholesterol levels in your body.
Statins do this by blocking your bodys production of an enzyme called HMG-CoA reductase. This is the enzyme your liver needs to make cholesterol. Blocking this enzyme causes your liver to make less cholesterol, which makes it easier for your body to remove cholesterol thats already in your blood. This lowers your cholesterol levels.
There are several real benefits to taking statins, and for many people, these benefits outweigh the drugs risks.
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How Can The Benefits And Risks Be Managed
There have been questions raised in the media over the benefits of statins. Peak health organisations have urged people who take statins to consult their doctors before stopping any prescribed medicines.
The benefits of statin treatment have been shown to outweigh the risk of possible side effects in most people at high risk of heart attack or stroke. If you are taking statins and have any concerns, talk to your doctor before making any changes.
The Royal Australian College of General Practitioners recommends that you regularly review with your doctor or specialist any medicines you are taking for high blood pressure or high cholesterol to assess the ongoing benefits and risks. For further information, visit the Choosing Wisely Australia website.
Other Benefits Of Statins
Organ transplant recipients may be prescribed statins because statins reduce the risk of cardiovascular problems after transplant. These drugs may also help lower the chance of rejection after an organ transplant, according to a 2013 study. However, more research is needed in this area.
Statins have anti-inflammatory properties that affect blood vessels, the heart, and the brain. This effect could also contribute to lowering the risk of blood clots, heart attack, and stroke.
Some combination medications also contain statins. Among them are:
- amlodipine/atorvastatin
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Increase Your Physical Activity
Physical activity increases levels of HDL cholesterol the good cholesterol that removes LDL cholesterol from the blood. Vigorous aerobic exercise is best.
If you havent been exercising much lately, gradually build up to the recommended amount of physical activity:
- People aged 18-64 years should do 30 to 60 minutes of moderate-intensity physical activity on most days of the week.
- People aged 65 years and over should aim for a total of 30 minutes of moderate physical activity on most days .
Moderate-intensity exercise is a level that increases your heart rate and breathing but allows you to keep talking. Vigorous intensity exercise makes your heart rate higher and makes you breathe more heavily.
Resistance training and muscle-toning exercises can increase HDL cholesterol. Aim to do this twice a week.
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Check If You Can Take Statins
Statins are not suitable for everyone.
Check with your GP that its safe to take statins if you:
- have ever had an allergic reaction to statins or other medicines
- have liver or kidney problems
- have severe lung disease or difficulty breathing
- take medicine for bacterial or viral infections
- take medicines call fibrates
- are of Asian origin, such as Japanese, Chinese, Filipino, Vietnamese, Korean or Indian your GP needs to choose the right start dose of Crestor to suit you
- over the age of 70 years
- drink large amounts of alcohol
- have an underactive thyroid
- have had muscular side effects when taking a statin in the past
- have had repeated or unexplained muscle aches or pains, or family history of muscle problems including fibromyalgia
- are trying to get pregnant, pregnant, or breastfeeding
Atorvastatin is also not suitable if youve had a stroke, or have phenylketonuria.
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Who Should Take Statins
Whether you need to take statins depends on your cholesterol levels and overall heart health. Cholesterol is the waxy substance found in the blood, and high levels of LDL or bad cholesterol can put you at risk of plaque buildup.
In the initial stages, a high LDL cholesterol level can be managed by lifestyle changes such as a healthy diet, exercise, and quitting smoking. However, if these measures fail or are not enough, your doctor may prescribe statins to lower your risk of developing cardiovascular disorders.
Pregnant or breastfeeding women should not take statins, and women trying to conceive must discontinue use. Generally, statins should be discontinued at least 6 weeks and preferably 12 weeks before planned conception.
How Statin Drugs Protect The Heart
More than 200 million people around the world take statin drugs for theirheart health. Shifting ideas about the risks and benefits of statins overthe years, however, have left some new patients confused about whetherthese drugs are rightor safefor them.
Traditionally, statins were viewed as purely cholesterol-lowering drugs. So it made sense just to use them for people with high cholesterol, explains Johns Hopkins cardiologist Michael Blaha, M.D. But weve learned that they also benefit people with lower levels of cholesterol who are at a high risk of heart disease. So we now think of statins as risk-reducing drugs.
This dramatic change in thinking means that people who once were not candidates for statins are now prescribed them to lower their risk of heart attack and stroke.
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Mechanisms Accounting For The Ezetimibe Induced Lipid Effects
NPC1L1 is highly expressed in the intestine with the greatest expression in the proximal jejunum, which is the major site of intestinal cholesterol absorption . Knock out animals deficient in NPC1L1 have been shown to have a decrease in intestinal cholesterol absorption . Ezetimibe binds to NPC1L1 and inhibits cholesterol absorption . In animals lacking NPC1L1, ezetimibe has no effect on intestinal cholesterol absorption, demonstrating that ezetimibeâs effect on cholesterol absorption is mediated via NPC1L1 . Thus, a major site of action of ezetimibe is to block the absorption of cholesterol by the intestine . Cholesterol in the intestinal lumen is derived from both dietary cholesterol and biliary cholesterol thus the majority is derived from the bile . As a consequence, even in patients that have very little cholesterol in their diet, ezetimibe will decrease cholesterol absorption. While ezetimibe is very effective in blocking intestinal cholesterol absorption it does not interfere with the absorption of triglycerides, fatty acids, bile acids, or fat-soluble vitamins including vitamin D and K.
The Dangers Of Statin Drugs
Over 900 studies have been published demonstrating the harmful side effects of the use of status.
A recent study published in Atherosclerosis shows that there is a 52% absolute increase in risk of atherosclerosis in people who started taking statin drugs. At the time of the study, none of the studys participants had any known cardiovascular disease.
In another study published in Diabetic Care, patients with type 2 diabetes and advanced atherosclerosis who used statins frequently had significantly higher amounts of arterial plaque when compared to patients who did not use statins as often. In a sub-group of participants not taking statins, the rate at which arterial plaque developed increased when they began taking statins.
Other studies have also documented serious side effects, including the following:
- Liver and pancreas failure due to increased enzymes caused by statin intake
- Muscle damage that can lead to loss of muscle cells, kidney failure and death
- Increased blood sugar and higher risk of type-2 diabetes
- Memory loss, depression, forgetfulness and other neurological side effects that have been seen to stop once the use of statins is also stopped
- Sexual dysfunction
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Foods With Added Sterols And Stanols
Sterols and stanols are plant chemicals which are a similar size and shape to cholesterol. They are absorbed from the intestines into the blood stream and block some cholesterol from being absorbed, lowering the cholesterol in your blood.
We get a small amount of sterols from plant-based foods such as vegetable oils, nuts, seeds, whole grains, fruits and vegetables, but its not enough to lower cholesterol. So, food companies have developed foods with plant sterols or stanols added to them, such as mini yogurt drinks, fat spreads, milk and yogurts.
These fortified foods lower your cholesterol gradually, over a few weeks, and how much depends on the amount you eat. Some experts believe they are the most effective single food for lowering cholesterol.
Who should eat foods with sterols and stanols added?
Sterols and stanols have been thoroughly researched, so they can be added to foods and are safe to eat.
They are suitable for:
- People with high cholesterol theres no real benefit if you dont have high cholesterol.
- Children with inherited high cholesterol such as familial hypercholesterolaemia with support from a doctor or dietitian.
- People taking statins sterols and stanols will help to lower your cholesterol further because they work in a different way to the statin.
They are not suitable for:
Aim for: one to three servings of fortified foods a day. This will give you 1.5 to 3g of stanols and sterols.
Three servings of: OR
One product a day:
Effect Of Bile Acid Sequestrants On Clinical Outcomes
The Lipid Research Clinics Coronary Primary Prevention Trial of cholestyramine vs. placebo was the first large drug study to explore the effect of specifically lowering LDL-C on cardiovascular outcomes . LRC-CPPT was a multicenter, randomized, double-blind study in 3,806 asymptomatic middle-aged men with primary hypercholesterolemia. The treatment group received cholestyramine 24 grams per day and the control group received a placebo for an average of 7.4 years. In the cholestyramine group total and LDL-C was decreased by 8.5% and 12.6% as compared to the placebo group. In the cholestyramine group there was a 19% reduction in risk of the primary end point accounted for by a 24% reduction in definite CHD death and a 19% reduction in nonfatal myocardial infarction. In addition, the incidence rates for new positive exercise tests, angina, and coronary bypass surgery were reduced by 25%, 20%, and 21%, respectively, in the cholestyramine group. The reduction in events correlated with the decrease in LDL-C levels . Of note, compliance with cholestyramine 24 grams per day was limited with many patients taking much less than the prescribed doses. These results indicate that lowering LDL-C with bile acid sequestrant monotherapy will reduce cardiovascular disease.
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What Statins Dont Do
Its also important to keep in mind that statins address just one risk factor for heart disease high cholesterol levels. There are many other risk factors that statins do not touch, like high blood sugar, insulin resistance, belly fat, high blood pressure, and high triglycerides .
To attack all these risk factors, your best bet is a healthy lifestyle like Pritikin, points out Dr. Danine Fruge, Medical Director at Pritikin.
How Pcsk9 Inhibitors Work
PCSK9 inhibitors work to lower cholesterol in patients whove been diagnosed with coronary artery disease, have a genetic propensity for high cholesterol or are at high risk for heart attack or stroke. PCSK9 inhibitors may also be effective alone for certain patients who cant tolerate a statin or cant achieve goal cholesterol levels while on other cholesterol-lowering medications.
This new class of drugs successfully lowers LDL by 50 to 70% when taken alone or in combination with a statin, says Brook, citing a study in the New England Journal of Medicine that shows PCSK9 inhibitors can actually prevent heart attacks and strokes. This benefit was shown even in patients taking statins who had LDL levels below 100 mg/dL who were previously thought to be well controlled, says Brook.
These PCSK9 inhibitors target PCSK9 proteins in the liver that destroy the livers receptors responsible for removing excess cholesterol from the blood. Because these proteins are destroyed, more receptors are then able to do their job, successfully lowering the amount of LDL cholesterol in the blood.
The PCSK9 inhibitor is injected in the skin of the abdomen or upper thigh every two to four weeks. Despite promising results, a major drawback for many patients is the cost.
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Mechanisms Accounting For Bile Acid Sequestrants Induced Lipid Effects
Bile acid sequestrants bind bile acids in the intestine, preventing their reabsorption in the terminal ileum leading to the increased fecal excretion of bile acids . This decrease in bile acid reabsorption reduces the size of the bile acid pool, which stimulates the conversion of cholesterol into bile acids in the liver . This increase in bile acid synthesis decreases hepatic cholesterol levels leading to the activation of SREBPs that up-regulate the expression of the enzymes required for the synthesis of cholesterol and the expression of LDL receptors . The increase in hepatic LDL receptors results in the increased clearance of LDL from the circulation leading to a decrease in serum LDL-C levels . Thus, similar to statins and ezetimibe, bile acids lower plasma LDL-C levels by decreasing hepatic cholesterol levels, which stimulates LDL receptor production and thereby accelerates the clearance of LDL from the blood.
The mechanism by which treatment with bile acid sequestrants improves glycemic control is unclear .
What Is Rhabdomyolysis
Rhabdomyolysis initially causes muscle pain and can worsen to cause significant muscle breakdown or kidney failure. In rare cases, it can be fatal.
The condition is more common in people who take a statin in combination with another drug that carries rhabdomyolysis risk or raises the level of statin in the blood.
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How Do Statins Help
Improving your cholesterol levels can help protect you from heart disease, heart attack, and stroke.
Your health care provider will work with you to lower your cholesterol by improving your diet. If this is not successful, medicines to lower cholesterol may be the next step.
Statins are often the first drug treatment for high cholesterol. Both adults and teenagers can take statins when needed.
Mechanisms Accounting For Bempedoic Acid Induced Lipid Effects
Bempedoic acid is a potent inhibitor of ATP-citrate lyase, which catalyzes the formation of acetyl-CoA in the cytoplasm . Acetyl-CoA is a precursor for the synthesis of cholesterol . The inhibition of ATP-citrate lyase by bempedoic acid decreases cholesterol synthesis in liver reducing hepatic intracellular cholesterol levels . Of note, bempedoic acid is a pro-drug and conversion to its CoA-derivative by very-long-chain acyl-CoA synthetase-1 is required for inhibition of cholesterol synthesis . Very-long-chain acyl-CoA synthetase-1 is highly expressed in the liver but is not expressed in adipose tissue, kidney, intestine or skeletal muscle . The inability of bempedoic acid to be activated in muscle and inhibit cholesterol synthesis suggests that bempedoic acid is unlikely result in muscle toxicity.
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Effect Of Bempedoic Acid On Clinical Outcomes
Currently there are no outcome studies determining the effect of bempedoic acid on atherosclerotic cardiovascular disease. The effect of bempedoic acid on cardiovascular disease is currently being evaluated in a large ~3.5-year clinical trial . In animal models of atherosclerosis, treatment with bempedoic acid had favorable effects on atherosclerosis . Moreover, genetic variants that mimic the effect of ATP citrate lyase inhibitors lower LDL-C levels and are associated with a decrease in cardiovascular disease suggesting that bempedoic acid will have favorable effects on reducing the risk of cardiovascular disease .
Are Statins Really Worth Taking For High Cholesterol
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Research has shown that statins are highly effective in reducing the risk of fatal heart attack and stroke. But some people are reluctant to take these life-saving drugs. They worry about taking medicine every day for the rest of their life or have heard that statins have undesirable side effects. What does science have to say about these concerns and others surrounding statins? We talked to UH interventional cardiologist Ian Neeland, MD, Director of the Center of Cardiovascular Prevention at University Hospitals, to learn more.
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