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 .
Effect On Bempedoic On Lipid And Lipoprotein Levels
EFFECT WITHOUT STATINS
In a study that randomized 345 patients with hypercholesterolemia .and a history of intolerance to statin to bempedoic acid or placebo bempedoic acid decreased LDL-C by 21.4%, non-HDL-C by 17.9%, and apolipoprotein B by 15% . One third of patients were on background non-statin therapy most commonly ezetimibe and fish oil. Triglyceride levels were not altered but there was a small decrease in HDL-C levels that was statistically significant .
IN COMBINATION WITH STATINS
Notably, the addition of bempedoic acid to atorvastatin 80mg per day was still capable of significantly decreasing LDL-C , non-HDL-C , and apolipoprotein B compared to placebo . The addition of bempedoic acid to high dose atorvastatin therapy did not cause meaningful changes in atorvastatin pharmacokinetics.
IN COMBINATION WITH STATIN AND EZETIMIBE
What Fibrates Are Available To Treat High Cholesterol Levels
Fibric acid derivatives
- Increased bleeding time.
Adenosine triphosphate-citric lyase inhibitors
The FDA has approved bempedoic acid to lower cholesterol. Bempedoic acid works in the liver to slow down cholesterol production. The medication comes in 180-mg tablets taken once per day with or without food. It should be taken with statin medications, but there are dosage limitations if taken with simvastatin or pravastatin.
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Mechanism Accounting For The Lomitapide Induced Lipid Effects
Lomitapide is a selective inhibitor of microsomal triglyceride transfer protein . MTP is located in the endoplasmic reticulum of hepatocytes and enterocytes where it plays a key role in transferring triglycerides onto newly synthesized apolipoprotein B leading to the formation of VLDL and chylomicrons . Loss of function mutations in both alleles of MTP results in abetalipoproteinemia, which is characterized by the virtual absence of apolipoprotein B, VLDL, chylomicrons, and LDL in the plasma due to the failure of the liver and intestine to produce VLDL and chylomicrons . Lomitapide by inhibiting MTP activity reduces the secretion of chylomicrons by the intestine and VLDL by the liver leading to a decrease in LDL, apolipoprotein B, triglycerides, non-HDL-C, and Lp .
Mechanism Accounting For The Statin Induced Lipid Effects
Statins are competitive inhibitors of HMG-CoA reductase, which leads to a decrease in cholesterol synthesis in the liver. This inhibition of hepatic cholesterol synthesis results in a decrease in cholesterol in the endoplasmic reticulum resulting in the movement of sterol regulatory element binding proteins from the endoplasmic reticulum to the golgi where they are cleaved by proteases into active transcription factors . The SREBPs then translocate to the nucleus where they increase the expression of a number of genes including HMG-CoA reductase and, most importantly, the LDL receptor . The increased expression of HMG-CoA reductase restores hepatic cholesterol synthesis towards normal while the increased expression of the LDL receptor results in an increase in the number of LDL receptors on the plasma membrane of hepatocytes leading to the accelerated clearance of apolipoprotein B and E containing lipoproteins . The increased clearance of LDL and VLDL accounts for the reduction in plasma LDL-C and triglyceride levels. In patients with a total absence of LDL receptors statin therapy is not very effective in lowering LDL-C levels.
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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.
Get Medical Advice From Your Doctor Not The Internet
Though statins are incredibly effective, there are many different forms of heart disease. Heart disease is still the No. 1 killer of men and women in our country, and the epidemic is spreading throughout the world. As long as the battle continues, well continue researching new ways to prevent and treat heart disease.
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Muscle Pain And Other Statin Side Effects
Taking a statin may give you some assurance that you’re doing all you can to avoid heart attack and stroke, but you may also experience side effects. Reported side effects include an increased chance of developing diabetes which is largely restricted to people who are already at risk for diabetes, and who can be monitored with glucose or hemoglobin A1c tests. Statin use has also been associated with difficulties with memory and reasoning, although there is no clear evidence that the drugs were responsible. In very rare cases, statins may cause liver problems or a potentially life-threatening breakdown in muscle cells.
However, the most common side effect is muscle pain and cramping. “In the real world about 15% to 20% of patients report myalgias, or muscle-related symptoms, with women reporting such symptoms more than men do,” says Dr. Samia Mora, a cardiologist at Harvard-affiliated Brigham and Women’s Hospital. It is unclear why these symptoms may be more common in women, but it could be because they tend to be older, have smaller bodies, and more additional health issues than men do when they begin to take the medications. Women are also more likely than men to have undiagnosed low levels of thyroid hormone, which increases the risk of statin-related side effects.
Statins And How Statins Work
Doctors also prescribe, usually if lifestyle changes are falling short, drugs like statins. Brand names include Lipitor, Crestor, Mevacor, Pravacol, and Zocor. Statins have been clearly shown to reduce blood cholesterol and prevent atherosclerosis, or heart disease. They work by reducing the livers production of cholesterol. They block an enzyme called HMG CoA Reductase that the liver uses to make cholesterol.
But other things are happening in the liver that statins do not affect. In addition to producing cholesterol, the liver helps clear excess cholesterol from the blood. It has tiny receptors that capture LDL bad cholesterol particles that are floating around. Like vacuum cleaners, these receptors suck this excess cholesterol up and out of the blood, which means theres much less cholesterol seeping into our artery walls, building plaque.
The problem is, a diet full of saturated fats, trans fat, and dietary cholesterol reduces the number and effectiveness of these LDL receptors. And theres nothing statins can do to counteract this process.
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What You Can Do About Muscle Pain From Statins
Keep track of any new symptoms that develop when you begin taking a statin, and report them to your doctor. Some symptoms may go away as you continue to take the medication. If you’re taking the statin preventively, your doctor may try to determine if your muscle pain symptoms are actually due to the statin by suggesting a brief holiday from the drug to see if they disappear when you’re not taking it. However, don’t stop taking a statin without telling your doctor. Although there are no proven remedies for statin-related muscle pain, the following may help.
Exercise.;There is some evidence that people who have exercised regularly before taking statins are less likely to experience muscle pain and cramping. Although gentle stretching may relieve muscle cramps, beginning a new vigorous exercise regimen while taking a statin may increase the risk of muscle pain.
Ramp up your lifestyle changes.;Commit to an exercise routine, lose weight if you need to, and adopt a heart- healthy eating plan such as the Mediterranean diet. Doing so may enable you to reduce your statin dosage, or possibly even lower your cholesterol enough to enable you to stop the statin. Even if a healthier lifestyle does not lower your lipid levels, it may still lower your long-term risk of heart disease and stroke.
Have a thyroid blood test.;If you have a low thyroid hormone level, taking replacement thyroid hormone pills may alleviate muscle pain and can also improve your lipid profile.
Truths About Statins And High Cholesterol
For every drop of scientific evidence that statins are safe and effective, there is a tidal wave of misinformation. Our patients are concerned about statin side effects theyve heard about from family or friends, or read about on the Internet.Statins are the gold-standard for high cholesterol treatment. Theyre a powerful medication, and theyve been proven to save the lives of many men and women living with or having a high risk of heart attack or stroke.But if statins are so effective, why are some people afraid to take them?As with any medication, there are risks associated with taking statins, but the benefits far outweigh the risks for the vast majority of high-risk patients.In an effort to put statin side effects into context and provide honest, scientific answers about statins and their use, weve put together a list of common questions our patients ask us:
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There Are Several Things You Can Do To Prevent Or Minimize The Aches And Pains That Might Accompany Statin Use
If you’re not taking a statin now, you may well be soon. These medications are commonly prescribed to lower “bad” LDL cholesterol and have been shown to reduce the risk of heart attack, stroke, and death. They are routinely recommended for people who have cardiovascular disease and for many people ages 40 to 75 who don’t have cardiovascular disease but have at least one risk factor and a 7.5% or greater risk of a stroke or heart attack in the next decade. Moreover, recent research indicates that they may benefit high risk individuals over age 75 as well.
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
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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 .
Continuing Statins With Supplementation
If side effects are your concern with statins, your doctor may suggest continuing to take the same dosage of your statin, but adding a supplement of CoQ10.
Some studies suggest that this plan could help reduce side effects. This is likely because statins can cause the levels of CoQ10 in your body to drop, leading to side effects such as muscle problems. Taking CoQ10 supplements could help reverse these side effects.
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Are You A Candidate For A Statin
Guidelines from the American College of Cardiology and American Heart Association recommend statin therapy for:
- Secondary prevention in people with established atherosclerotic cardiovascular disease.
- People with an LDL cholesterol level of 190 milligrams per deciliter or higher, due to a genetic condition.
- People with diabetes ages 40 to 75 with an LDL level over 70 mg/dL and no atherosclerotic cardiovascular disease.
- Non-diabetic adults ages 40 to 75 with a 20% or greater likelihood of developing atherosclerotic cardiovascular disease in the next 10 years .
- Non-diabetic patients ages 40 to 75 with an LDL level of 70 to 189 mg/dL and a 10-year ASCVD risk of 7.5% to less than 20% if the risk estimate and presence of certain risk-enhancing factors* favor treatment.
* These factors include a family history of ASCVD, LDL levels persistently 160 mg/dL, triglyceride levels persistently 175 mg/dL, chronic kidney disease, ethnicity, inflammatory diseases, metabolic syndrome, and results of high-sensitivity C-reactive protein, lipoprotein, and apolipoprotein B. Note: The guidelines recommend considering coronary artery calcium scoring for people at intermediate risk in whom a decision about starting statin treatment remains uncertain.
How Can I Accelerate My Results
Sometimes diet, exercise, weight management, and smoking cessation are simply not enough or can not produce the quick results needed by these people in the high-risk category of heart attack or stroke. In these cases, your doctor will prescribe you probably one of the several types of cholesterol-lowering medications. The most likely candidate will be one of the statins which significantly reduce the amount of cholesterol produced by the liver. Statins can reduce LDL by 30 to 60 percent in a matter of weeks. Although they can produce impressive results, they come with a long list of side effects that need to be discussed with your doctor before making a decision.
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Getting The Most From Your Treatment
- Try to keep your regular appointments with your doctor. This is so that your doctor can check on your progress. You will need to have blood tests from time to time. These are to measure your cholesterol level and also to check that your liver has not been affected by taking atorvastatin.
- Your doctor will give you advice about eating a healthy diet, cutting down on the amount of alcohol you normally drink, reducing the amount of salt in your diet, stopping smoking, and taking regular exercise. Following this advice will also help you to reduce your risk of developing heart and blood vessel disease.
- Do not drink more than one or two small glasses of grapefruit juice a day. This is because a chemical in grapefruit juice can increase the amount of atorvastatin in your bloodstream, which can make side-effects more likely.
- Women taking atorvastatin must avoid getting pregnant. Make sure you have discussed with your doctor which types of contraception are suitable for you and your partner.
- Treatment with atorvastatin is usually long-term unless you experience an adverse effect. Continue to take the tablets unless you are advised otherwise by your doctor.
Dietary Dos And Donts
When taking Lipitor, its important to follow the exercise and dietary recommendations made by your doctor or dietitian. Typically, patients who take the medication are told to eat a low-fat, low-cholesterol diet.
The U.S. Department of Health and Human Services recommends that people looking to lower their cholesterol have:
- Less than 7 percent of daily calories from saturated fat
- Less than 200 mg a day of cholesterol
- 25 percent to 35 percent of daily calories from total fat
The drugs label warns users to avoid drinking large amounts of grapefruit juice while taking the drug. This means users should not drink more than 1.2 liters of grapefruit juice per day. Grapefruit juice contains one or more components that inhibit CYP34A, an important enzyme found in the liver, and it can increase plasma concentrations of atorvastatin.
Experts also recommend at least 30 minutes a day of moderate intensity physical activity such as brisk walking, but talk with your doctor to determine what is appropriate for you.
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How Do Atorvastatin And Simvastatin Work
and are both statins, so they work in similar ways to lower cholesterol. You may already know that cholesterol can come from your diet, but did you know that you also make cholesterol in your liver? Statins like atorvastatin and simvastatin prevent your liver from making cholesterol.
Statins are the go-to medication for treating high cholesterol and preventing a heart attack or stroke. They are especially good at lowering levels of LDL cholesterol, the kind that can clump together in your blood when theres too much. This can eventually lead to fatty material forming on your blood vessel walls, known as atherosclerosis. Plaques can block blood flow, which raises your risk for a heart attack or stroke.