New Drug Combo Shows Promise In Fight Against High Cholesterol
Adding certain drugs to your statin can reduce cholesterol levels better than taking a statin alone. Here, a Michigan Medicine doctor breaks it all down.
If youve ever been diagnosed with high cholesterol, also known as hyperlipidemia, your doctor has probably prescribed a statin.
And while statins have been the go-to drug for managing cholesterol for nearly 25 years, theres a new weapon in the fight. Recent studies suggest that adding a new class of medications either a PCSK9 inhibitor or pure EPA fish oil to statins may help reduce cholesterol faster and by greater levels than taking a statin alone.
Equally important is their success in reducing the number of cardiovascular events such as heart attack and stroke in at-risk patients, says cardiovascular medicine and lipid specialist Robert D. Brook, M.D., of the Michigan Medicine Frankel Cardiovascular Center.
These new medications represent significant advancements in the world of hyperlipidemia, he says.
How To Cope With Side Effects
What to do about:
- stomach pain try to rest and relax. It can help to eat and drink slowly and have smaller and more frequent meals. Puttinga heat pad or covered hot water bottle on your stomach may also help. If you’re in a lot of pain, speak to a pharmacist or doctor.
- diarrhoea drink lots of fluids, such as water or squash, to avoid dehydration. Speak to a pharmacist if you have signs of dehydration such as peeing less than usual or having dark, strong-smelling pee. Do not take any other medicines to treat diarrhoea without speaking to a pharmacist or doctor. Speak to a doctor if diarrhoea lasts for more than a week after you start ezetimibe.
- farting try to not eat foodsthat cause wind . Eat smaller meals, eat and drink slowly, andexercise regularly. There are pharmacy medicines that may also help, such as charcoal tablets or simeticone. Peppermint tea may also help.
- feeling tired try to relax when possible and avoid intense exercise to see if that helps. If these symptoms do not go away after 1 to 2 weeks, ask a pharmacist or doctor for advice.
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.
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Atp Citrate Lyase Inhibitors
What it is: Bempedoic keeps your liver from processing cholesterol. It is designed to help lower LDL in adults who have HeFH. It can also help lower the LDL in people with atherosclerotic cardiovascular disease .
Side effects: Upper respiratory tract infection, muscle spasms, excess uric acid in the blood, back pain, belly pain or discomfort, bronchitis, anemia, and higher liver enzymes.
Who Needs Cholesterol Medicines
- You have already had a heart attack or stroke, or you have peripheral arterial disease
- Your LDL cholesterol level is 190 mg/dL or higher
- You are 40-75 years old, you have diabetes, and your LDL cholesterol level is 70 mg/dL or higher
- You are 40-75 years old, you have a high risk of developing heart disease or stroke, and your LDL cholesterol level is 70 mg/dL or higher
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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 .
Mechanism Accounting For The Pcsk9 Inhibitor Induced Lipid Effects
The linkage of PCSK9 with lipoprotein metabolism was first identified by Abifadel and colleagues in 2003, when they demonstrated that certain mutations in PCSK9 could result in the phenotypic appearance of Familiar Hypercholesterolemia . Subsequent studies demonstrated that gain of function mutations in PCSK9 are an uncommon cause of Familiar Hypercholesterolemia . In 2005 it was shown that loss of function mutations in PCSK9 resulted in lower LDL-C levels and this decrease in LDL-C levels is associated with a reduction in the risk of cardiovascular events .
The main route of clearance of clearance of plasma LDL is via LDL receptors in the liver . When the LDL particle binds to the LDL receptor the LDL particle- LDL receptor complex is taken into the liver by endocytosis . The LDL particle and the LDL receptor then disassociate and the LDL lipoprotein particle is delivered to lysosomes where it is degraded and the LDL receptor returns to the plasma membrane . After endocytosis LDL receptors recirculate back to the plasma membrane over 100 times.
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Effect Of Bile Acid Sequestrants On Lipid And Lipoprotein Levels
The major effect of bile acid sequestrants is to lower LDL-C levels in a dose dependent fashion. Depending upon the specific drug and dose the decrease in LDL-C ranges from approximately 5 to 30% . The effect of monotherapy with bile acid sequestrants on LDL-C levels observed in various studies is shown in .
Pharmacokinetics And Drug Interactions
Omega-3 ethyl esters and fatty acids are absorbed by the GI tract similar to other dietary lipids. It is worth noting that omega-3-free fatty acids are directly absorbed by the small intestine and are not dependent on pancreatic lipases for absorption. Thus, absorption of omega-3-fatty acids is not decreased in patients with pancreatic insufficiency and therefore may be preferred in patients with pancreatic disease. Additionally, the bioavailability of omega-3-fatty acids with a low fat diet was greater than omega-3-ethyl esters while there was little difference between these different formulations with a high fat diet .
Drug interactions have not been seen with omega-3-fatty acids .
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How Long Will I Need Cholesterol Medication
Typically, people who take cholesterol medication need it for the rest of their lives, and youre more likely to need it as you get older. However, children and teens can have high cholesterol, too. Lifestyle changes can often prevent the need for medication or work with medication to lower your risk of coronary artery disease.
The Effects Of Alcohol On Triglycerides And Ldl
Moderate alcohol intake can increase HDL cholesterol, and that’s a plus. It also might increase insulin sensitivity and cause other positive health responses. The recommendation for alcohol use is mild or moderate consumption. Using alcohol in moderation is considered one drink a day for women and two drinks a day for men.
Note: The beneficial effects of alcohol are not great enough to endorse the use of alcohol if you do not already drink. Talk with your health care provider about the pluses and minuses of alcohol for you and your health.
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What Are The Precautions For Taking Cholesterol Medication
Looking for the best cholesterol medication means you need to know what precautions to take. Each drug has side effects like diarrhea, constipation, nausea, muscle soreness/pain/weakness, stomach pain, bloating, gas, fatigue, cramps, abdominal pain, flushing , peptic ulcers, vomiting, gout, high blood sugar, dizziness, heart palpitations, sweating, shortness of breath, chills, indigestion, belching, swelling, itching, rashes, hives, flu, and swelling of nasal passages.
Additionally, statins can negatively react when taken in combination with grapefruit juice. Injectable medications may also cause some bruising or pain on the area that was injected.
These side effects do not show up together or all at once. Most of them are also mild. To properly manage these, you need to consult with your doctor before taking any medication. Even the best cholesterol medication can only efficiently work if taken correctly, in correct dosages and amounts.
Side effects like these are the primary reason why some people including doctors prefer to go more natural on their cholesterol medication choices.
Effect On Inclisiran On Lipid And Lipoprotein Levels
HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
The effect of inclisiran on LDL-C levels was determined in patients with heterozygous familial hypercholesterolemia who were randomized to receive subcutaneous injections of inclisiran 284mg or placebo on days 1, 90, 270, and 450 . The mean baseline LDL-C level was 153±54mg/dl and 90% of the patients were receiving statins with most on high intensity statins . At day 510 LDL-C levels were reduced by 47.9% compared to placebo . The reduction in LDL-C was similar in all genotypes of familial hypercholesterolemia. Total cholesterol was reduced by 33%, non-HDL-C by 44%, Lp by 17.2%, and triglycerides by 12%. HDL-C and hsCRP were not markedly altered.
HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
A small study reported that inclisiran treatment lowered LDL-C levels in 3 of 4 patients with homozygous familiar hypercholesterolemia but less than that seen in individuals with fully functioning LDL receptors .
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Effect Of Fibrates On Cardiovascular Outcomes
There have been a number of studies that have examined the effect of a variety of different fibrates on cardiovascular disease. We will describe the major studies below.
A separate meta-analysis has focused on the effect of fibrates on cardiovascular disease in patients with pre-existing disease . It included 13 trials involving a total of 16,112 participants. For the primary composite outcome of non-fatal stroke, non-fatal myocardial infarction, and vascular death, fibrate therapy significantly decreased risk by 12% 0.88, 95% 0.83 to 0.94). Fibrates were effective for preventing myocardial infarction . Fibrates were not effective in lowering all-cause mortality , death from vascular causes , or stroke events . Since clofibrate has been discontinued due to safety concerns, the data were reanalyzed excluding clofibrate trials. Without clofibrate, fibrates no longer significantly reduced the primary outcome but were still effective in preventing myocardial infarctions . Subgroup analyses showed the benefit of fibrates on the primary composite outcome to be consistent irrespective of age, gender, and diabetes mellitus.
SUMMARY OF OUTCOME STUDIES
Choose Foods That Help Improve Your Ldl And Hdl Levels
Following a healthy eating plan can play a big role in your overall health, including your blood sugar and blood lipid control. What you eat and your cholesterol levels go hand in hand.
Foods that can help lower cholesterol:
Fiber , healthy fats , and plant stanols or sterols have all been shown to help lower cholesterol.
Other ways to improve cholesterol:
— Reduce sugar intake: Cut the amount of added sugars you eat. This is especially important for people with high triglycerides. The grams of sugars on the Nutrition Facts label of a food package, however, doesn’t tell you if sugars have been added . Instead, look at the ingredients list for items such as sugar, corn syrup, high fructose corn syrup, molasses, maple syrup, or agave to see if there are added sugars in the product. Natural sugars, such as those found in fruit and dairy products, are also counted as sugars on the Nutrition Facts label. Limit how much sugar you use to sweeten drinks or in recipes.
— Limit high-cholesterol foods: People with diabetes should consume no more than 200 milligrams of cholesterol per day, according to the ADA.
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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 .
Cholesterol Medication: Types Benefits And Side Effects
Elevated cholesterol levels affect millions of adults across the United States and Europe. While you may not feel any health effects of high cholesterol at first, over time it can lead to a host of health problems, especially heart disease. Fortunately, this condition is easily managed with diet, lifestyle changes, and medication. Your healthcare provider can help you decide which of the many types of cholesterol medications is right for you.
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What Are The Types Of Fibrate Drugs
There are several types of fibrates. You may take:
Last reviewed by a Cleveland Clinic medical professional on 02/10/2022.
References
- American Heart Association. Cholesterol Medications. Accessed 2/10/2022.
- Blais JE, Kin Yi Tong G, et al. Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials. 2021 Feb-. PLoS ONE 16: e0246480. Accessed 2/10/2022.
- Singh G, Correa R. Fibrate Medications. Treasure Island : StatPearls Publishing 2021 Jan-. Accessed 2/10/2022.
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Do I Need Cholesterol Medication
- Moving your body for 30 minutes each day. Exercise can help raise HDL cholesterol and lower LDL cholesterol, especially for anyone who is overweight.
- Quitting smoking. Smoking raises LDL cholesterol and lowers HDL cholesterol, especially in women.
When lifestyle changes arent enough to control your cholesterol, medication can be an option.
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How Do Fibrate Drugs Work
Fibrates reduce the amount of very-low-density lipoprotein your liver makes. VLDL particles carry triglycerides to other parts of your body. By limiting how much VLDL your body makes, these medicines lower your triglyceride levels.
Fibrate drugs also increase the amount of apolipoproteins A-I and A-II your liver makes. These two proteins help create HDL cholesterol. Creating more of these proteins increases your HDL cholesterol levels.
How To Lower Triglycerides Fast Without Medications
Unlike many illnesses, much of the treatment centered around how to lower triglycerides actually has a lot to do with lifestyle factors like diet and physical activity. In fact, moderate to slightly high levels of triglycerides may be managed in this way alone, without the use of prescription medications. Since what raises triglycerides in the first place is often the foods that we eat, it is not a wonder that a mere change in ingestibles can provide long term benefits in the form of lower triglycerides levels. And, the long term management of the amounts of these fats circulating in the blood can often be well managed with a diet to lower triglycerides combined with an increase in moderate exercise.
Fats are also best left alone as much as possible for anyone trying to stave off ever rising levels of the manufactured blood fats. As such, fried foods and those that contain trans fat or saturated fat should be eliminated from diets entirely. Not only does this decrease the likelihood that triglycerides will remain on the rise, a low fat diet also contributes to a reduced risk of obesity. Being overweight or obese is a major contributing factor to the increase of triglycerides in the blood, and adhering to a low fat diet can reduce this risk dramatically.
References:
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Effect Of Pcsk Inhibitors On Lipid And Lipoprotein Levels
There are a large number of studies that have examined the effect of PCSK9 inhibitors on lipid and lipoprotein levels. A meta-analysis of 24 studies comprising 10,159 patients reported a reduction in LDL-C levels of approximately 50% and in an increase in HDL of 5-8% . Notably, in 12 RCTs with 6,566 patients, Lp levels were reduced by 25-30% . The higher the baseline Lp the greater the reduction with treatment . It should be recognized that most LDL-C lowering drugs do not lower Lp levels. PCSK9 inhibitors have not been shown to decrease hs-CRP levels .
MONOTHERAPY
Both alirocumab and evolocumab have been studied as monotherapy vs. ezetimibe. In the Mendel-2 study patients were randomly assigned to evolocumab, placebo, or ezetimibe . In the evolocumab group, LDL-C levels decreased by 57% while in the ezetimibe group LDL-C levels decreased by 18% compared to placebo. Additionally, non-HDL-C was decreased by 49%, apolipoprotein B by 47%, triglycerides by 5.3% , and Lp by 18.5% while HDL levels increased by 5.5% in the evolocumab treated subjects. In a study of alirocumab vs. ezetimibe, LDL-C levels were reduced by 47% in the alirocumab group and 16% in the ezetimibe group . In addition, alirocumab decreased non-HDL-C by 41%, apolipoprotein B by 37%, triglycerides by 12%, and Lp by 17% and increased HDL by 6%. Thus, PCSK9 monoclonal antibodies are very effective in lowering pro-atherogenic lipoproteins when used in monotherapy and have a more robust effect than ezetimibe.
Drugs That Work In Your Intestines
What they are: Your doctor may call these âbile acid resinâ drugs or âbile acid sequestrants.â The work inside your intestines. They attach to bile from the liver and keep it from being absorbed back into your blood. Bile is made largely from cholesterol, so these drugs whittle down the body’s supply of cholesterol.
Examples include:
A different type of drug, ezetimibe , lowers âbadâ LDL cholesterol by blocking cholesterol absorption in your small intestine. Studies have found that in people who have had a heart attack, it can make a small cut in the risk of heart âevents,â such as another heart attack, when you also take a statin.
Side effects: For bile acid drugs, the most common side effects are constipation, gas, and upset stomach. For ezetimibe, the most common ones include muscle or back pain, diarrhea, and abdominal pain.
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