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.
Statin Risks And Benefits
Are statins safe? For most people, the answer is a resounding yes, according to a 2014 Johns Hopkins meta-analysis of 20 years worth of published research. It showed that the risks of long-term use of statin drugs are low and the potential benefits are very high. Researchers combed through hundreds of papers that had studied statins since 1994 to determine the evidence of side effects.
Their review, published in British Medical Journal, found an increase in the risk of muscle aches. There was also a modest risk of elevated blood glucose, which can tip some people into developing type 2 diabetes. Whats unclear is whether those people, who also had other risk factors for diabetes, would have developed the condition anyway. Statins dont cause memory loss or cataracts, as has been claimed in the past. For most at-risk patients, the benefits far exceed the risks, the researchers concluded. Of course, if you notice any unusual effects after beginning statin therapy, tell your doctor.
We know a lot about statins because theyve been around for a long time and taken by so many people, Blaha says. The scale clearly tips to benefits in most at-risk patients.
Why did my doctor prescribe statins if my cholesterol is normal?
Common Statin Side Effects
The most common side effects of statins include:
- Headache
More severe but rare side effects of statins include:
- Severe muscle pain
- Rhabdomyolysis, or muscle breakdown
- Serious liver problems
Although rare, statins can cause a condition called rhabdomyolysis. Rhabdomyolysis results in life-threatening muscle damage. The breakdown of muscle tissue can lead to the release of a certain protein called myoglobin into the bloodstream, which can damage the kidneys. Symptoms of rhabdomyolysis include severe muscle pain, liver damage, and kidney failure.
The use of statins, especially in high doses, has also been associated with memory loss. However, this side effect is rare, and it is reversible after discontinuation of therapy. On the other hand, some studies have shown that statins are protective against dementia and Alzheimers disease.
Serious side effects associated with statins are often rare and associated with high doses. This list of side effects is not comprehensive. Speaking with a healthcare professional is the best way to get a complete list of side effects in order to determine whether taking a stain is suitable for you. If you experience side effects with a certain statin, your doctor may recommend a different statin.
Tell your doctor if you have a history of any of the following before taking a statin:
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Effect Of Lomitapide On Clinical Outcomes
There are no clinical outcome trials but it is presumed that lowering LDL-C levels in patients with Homozygous Familial Hypercholesterolemia will reduce cardiovascular events. After initiating lomitapide therapy 1.7 cardiovascular events per 1000 patient months on treatment was observed vs. 26.1 cardiovascular events per 1000 patient months in a comparison cohort .
How Long Does It Take Cholesterol To Go Down
People who need to use medications such as statins to lower their cholesterol should see their cholesterol levels fall quickly.
These medications may work in a matter of weeks, and they generally work to a larger degree than lifestyle changes.
However, because diet affects the levels of cholesterol in the body, doctors commonly recommend that people make changes to their diet and lifestyle in addition to taking medications.
Making simple changes to the diet and lifestyle can help reduce cholesterol.
These changes vary depending on how strictly a person adheres to their diet, as well as other factors, such as exercise and weight loss.
Some dietary changes may cause minor reductions in cholesterol in as little as
Dietary and lifestyle changes and medications can all help lower blood cholesterol levels.
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What Is The Difference Between Statin Drugs
Each of the statin drugs works in the same way in your body. However, there are slight differences in their effect on the cholesterol and the way they are processed in your body.
How well they work
The most effective drugs to reduce LDL cholesterol and atorvastatin, rosuvastatin, simvastatin. The least effective statin drugs to reduce LDL cholesterol are fluvastatin and pravastatin.
Drug Interactions
Most statin drugs are metabolized in the liver by enzymes that are also involved in the metabolism of other drugs. This means that they can interact with each other and there is an increased risk of side effects. Fluvastatin, pravastatin, and rosuvastatin tend to interact with other drugs less often than atorvastatin or simvastatin.
Time of Dose
It is best to take a dose of simvastatin, fluvastatin or pravastatin at nighttime because the drug is more effective when taken at this time. However, atorvastatin and rosuvastatin are not affected by this and can be taken at any time.
People With Cardiovascular Disease Caused By Atherosclerosis
This includes people who have had:
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A heart attack or other problems from blockage of the coronary arteries of the heart
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A stroke or mini-stroke or blockage of carotid arteries in the neck
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Leg pain caused by blockage of peripheral arteries
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Aneurysm or bulging of the abdominal aorta
The goal of using statins is to prevent further problems, like a second heart attack.
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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.
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 Mipomersen On Clinical Outcomes
There are no clinical outcome trials but it is presumed that lowering LDL-C levels in patients with Homozygous Familial Hypercholesterolemia will reduce cardiovascular events. In a study comparing cardiovascular events in patients with Homozygous Familial Hypercholesterolemia in the 24 months prior to initiating mipomersen therapy and after initiating mipomersen revealed a decrease in events . In this trial mipomersen resulted in a mean absolute reduction in LDL-C of 70 mg/dL , non-HDL cholesterol of 74 mg/dL , and Lp of 11 mg/dL .
Lifestyle Therapy: The First Step
With so many people in need and so many medications available, it’s understandable that both doctors and their patients are tempted to rely on medications to improve unhealthy cholesterol levels. That’s a mistake. Instead, lifestyle therapy is the place to start. That means avoiding tobacco in all its forms. It also means choosing foods low in saturated fat, trans-fatty acids, and cholesterol while favoring foods that provide heart-healthy omega-3 and monounsaturated fats and large amounts of dietary fiber. It also requires regular exercise, which can be as simple as walking at a moderate pace for at least 30 minutes nearly every day. And the combination of a good diet and regular exercise should help men achieve another important goal, weight control.
Lifestyle therapy can improve cholesterol levels, and certain foods can provide extra help . But even with clean living, many people need medication to achieve optimal cholesterol levels, particularly when they have to reduce their LDL levels to 100 mg/dL or less. It’s important to keep up a good diet and exercise program even if you take medication. And if you can’t take a statin, here is a rundown of other medications that can help Table 3 summarizes their effects on blood lipids and compares them to the statins.
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Effect On Mipomersen On Lipid And Lipoprotein Levels
In the pivotal trial, 51 patients with Homozygote Familial Hypercholesterolemia on treatment were randomized to additional treatment with mipomersen or placebo and followed for 26 weeks . Mipomersen lowered LDL-C levels by 21% and apolipoprotein B levels by 24% compared to placebo. In addition, non-HDL-C was decreased by 21.6%, triglycerides by 17%, and Lp by 23% while HDL and apolipoprotein A-I were increased by 11.2% and 3.9% respectively.
Mipomersen has also been studied in patients with Heterozygous Familial Hypercholesterolemia. In a double-blind, placebo-controlled, randomized trial, patients on maximally tolerated statin therapy were treated weekly with subcutaneous mipomersen 200 mg or placebo for 26 weeks . LDL-C levels decreased by 33% in the mipomersen group compared to placebo. Additionally, mipomersen significantly reduced apolipoprotein B by 26%, triglycerides by 14%, and Lp by 21% compared to placebo with no significant changes in HDL-C levels. In an extension follow-up study the beneficial effects of mipomersen were maintained for at least 2 years .
In a meta-analysis of 8 randomized studies with 462 subjects with either non-specified hypercholesterolemia or Heterozygous Familial Hypercholesterolemia, Panta and colleagues reported that mipomersen decreased LDL-C levels by 32% compared to placebo . Additionally, non-HDL-C was decreased by 31%, apolipoprotein B by 33%, triglycerides by 36%, and Lp by 26% with no effect on HDL levels.
Mechanism Accounting For The Evinacumab Induced Lipid Effects
ANGPTL3 inhibits lipoprotein lipase activity thereby slowing the clearance of VLDL and chylomicrons resulting in an increase in plasma triglyceride levels . Mice deficient in ANGPTL3 have lower plasma triglyceride levels while mice overexpressing ANGPTL3 have elevated plasma triglyceride levels . Evinacumab by inhibiting the ability of ANGPTL3 to inhibit LPL activity will accelerate the clearance of TG rich lipoproteins decreasing plasma triglyceride levels . Furthermore, ANGPTL3 has also been shown to reduce endothelial lipase activity . Endothelial lipase is a phospholipase that catabolizes phospholipids on HDL and accelerates HDL clearance . Evinacumab by inhibiting the ability of ANGPTL3 to inhibit endothelial lipase activity will lead to a decrease in HDL levels .
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What Are Statins Used For
Statins are the most effective drugs currently available to lower the LDL cholesterol in the blood and can usually reduce the LDL concentration by 30% to 50%. They can also help to reduce triglyceride and increase HDL cholesterol concentrations slightly. As a result, if you have a high risk of cardiovascular disease, a statin drug can reduce your risk of suffering from a myocardial infarction, stroke, revascularization procedures,and death.
There are several reasons that your doctor might recommend a statin drug for you. It might be because you have:
- High levels of cholesterol in your blood
- High levels of triglycerides and cholesterol in your blood
- A high risk of CHD
However, statins should only be usedin combination with diet and lifestyle alterations and not as a substitute for healthy living choices.
Statin Use During A Heart Attack
If youve had a heart attack or are dealing with any other type of acute coronary event, such as interventions like bypass surgery or angioplasty, chances are your physician will prescribe a statin during and immediately after the event, and for good reason. It is generally accepted in the medical community that statins may have some value independent of lowering LDL cholesterol, probably anti-inflammatory in nature.
But doctors do not have clear answers to the following: What statin is best? What dosage? How long should the patient be on it? Usually, high doses are prescribed immediately after the event and are then tapered to doses necessary to maintain target values .
There is much about statins we physicians do not know, states Dr. Ronald Scheib, MD, FACC, FACP, former Chief of Section of Cardiovascular Medicine at the Miami Heart Institute. We do know that toxicity is a clear danger.
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What Else Should I Know About Atherosclerosis And Statins
Statins are used specificially for preventing and treating atherosclerosis that causes chest pain, heart attacks, strokes, and intermittent claudication . Lupus, medications such as corticosteroids, family history, and other factors can predispose a person to atherosclerosis however, only your doctor can decide whether statins are the right choice for you based on your total cholesterol level, LDL level, and other risk factors. Most people are placed on statins only if lifestyle changes are not sufficient enough in reducing their cholesterol levels. However, keep in mind that if you begin taking a statin, you may be on it for the rest of your life.
Eating a low-fat, low-calorie diet is also essential in preventing or slowing atherosclerosis. Focus on what you can eat, not what you cant. For example, fish, vegetables, fruits, whole grains, and legumes are all great choices. In addition, try to limit stress and exercise regularly. Walking, biking, stretching, yoga, and Tai chi are all great activities for people with lupus because they are easier on your joints but help to improve muscle, bone, and heart health. If you are overweight, weight loss can help to reduce your cholesterol.
Cholesterol Lowering Drug Can Help Prevent Heart Attacks Strokes
High cholesterol is a familiar warning sign for cardiovascular disease. While some people can control their cholesterol through diet and exercise, others also may need medication. Thats where statins come in.
Statins are commonly used to lower cholesterol levels and reduce the risk of heart attack and stroke. Millions of people who have heart disease or are at high risk take them and help protect their hearts that way.
Who needs statins?
Treatment for high cholesterol is based on overall risk for cardiovascular disease.
Your doctor will consider all your risk factors, including cholesterol levels and medical conditions, says Todd Hitchcock, MD, a cardiologist at Scripps Clinic Carmel Valley. If you doctor recommends statins, its because you are at risk for heart disease or stroke.
Other risk factors include smoking, lack of exercise, high blood pressure, diabetes, high blood sugar levels, excess weight or obesity, family history of heart disease and older age.
Statins are also recommended for people whove had a heart attack or stroke even if they dont have high cholesterol.
What is cholesterol?
Cholesterol is a fatty substance made by the liver that travels through the blood. There are two types of cholesterol. One is good. The other is bad.
HDL cholesterol is the good cholesterol. It helps remove the bad cholesterol and protect the arteries.
Why is high cholesterol bad?
How do statins work?
What are the risks and benefits of statins?
- Heart & Vascular
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What Is Cholesterol
Our bodies make and need some cholesterol to work. But too much can hurt your heart health. Very high levels can promote the buildup of cholesterol, fat and other substances also called plaque in the walls of arteries. This buildup can block blood flow.
Unlike a headache, chest cold or stomach upset, high cholesterol usually has no symptoms. But its a big red flag when it comes to the chance that someone will develop heart or blood vessel problems.
How Do Statins Work
Statins work by slowing down the production of LDL-cholesterol in the liver, where its made. Because the liver isn’t making so much cholesterol, it then takes cholesterol out of your blood to make bile with, so your blood cholesterol levels fall.
Statins slow down LDL-cholesterol production by blocking an enzyme called HMG-CoA-Reductase the medical name for statins is HMG-CoA Reductase inhibitors. Enzymes are proteins in the body which speed up normal processes. In this case, LDL production.
Statins can lower your triglycerides
As well as lowering your LDL-cholesterol, statins can lower your triglycerides too, and high triglycerides are linked to liver disease, heart disease and diabetes.
Statins can raise HDL cholesterol
Statins can sometimes raise your HDL-cholesterol the type of cholesterol which helps to clear the fat from of your arteries.
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