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
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.
Side Effects Of Statins
Many people who take statins experience no or very few side effects.
Others experience some troublesome, but usually minor, side effects, such as diarrhoea, a headache or feeling sick.
Your doctor should discuss the risks and benefits of taking statins if they’re offered to you.
The risks of any side effects also have to be balanced against the benefits of preventing serious problems.
A review of scientific studies into the effectiveness of statins found around 1 in every 50 people who take the medicine for 5 years will avoid a serious event, such as a heart attack or stroke, as a result.
Find out more about the side effects of statins.
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What Are Statins Used For
Having high levels of ‘bad’ cholesterol in the blood can increase the risk of cardiovascular disease, such as heart attack and stroke. Statins are used to lower LDL cholesterol, and this helps lower the risk of cardiovascular disease.
Statins are considered the most effective group of cholesterol-lowering medicines available and work by blocking cholesterol production in the liver.
Statins are used in combination with other ways of lowering cholesterol, including eating a healthy diet, managing weight and exercising.
Cholesterol Levels In Dialysis Patients
In a study of dialysis patients, those with higher cholesterol levels had lower mortality than those with low cholesterol.51 Yet the authors claimed that the inverse association of total cholesterol level with mortality in dialysis patients is likely due to the cholesterol-lowering effect of systemic inflammation and malnutrition, not to a protective effect of high cholesterol concentrations. Keeping an eye on further funding opportunities, the authors concluded: These findings support treatment of hypercholesterolemia in this population.
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Mistake : Youre Not Exercising Enough
Diet alone is often not enough. It should be combined with exercise, says Michos. When it comes to exercise, the equation is pretty simple: Being sedentary equals lower levels of HDL, according to the AHA. You can lower both cholesterol and high blood pressure by doing at least 150 minutes of moderate-intensity exercise, such as walking, bicycling, swimming, or even doing yard work, each week.
Even more good news: A review published in November 2018 in the journal BioMed Research International found that both low- and moderate-intensity aerobic exercise led to a significant reduction in total cholesterol, including LDL.
Eating Healthy But Your Ldl Is Still High
If you have transitioned to a whole food, plant-based diet and still have high LDL, you may want to take a closer look at your family history, diet, and lifestyle.
Most cases of high cholesterol are not caused by a single inherited condition but result from a combination of lifestyle choices and the effects of variations in many genes. Familial hypercholesterolemia occurs because of a genetic defect on chromosome 19. Its an inherited disorder that makes it harder for your body to remove LDL cholesterol from your blood. However, your genes are not your destiny, and the first line of treatment for FH is lifestyle modification.
Lower Your Fat Intake
Exercise
Being physically active is another way to maintain healthy cholesterol levels, particularly for strength training, aerobics, and high-intensity exercise such as HIIT . However, even low-intensity exercise has been shown to increase HDLs anti-inflammatory and antioxidant capabilities. Exercise can also help to lower LDL cholesterol when combined with dietary changes and weight loss.
Diet or Statins?
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How Fast Do Statins Work
Many doctors are prescribing statins to lower cholesterol in their patients. High cholesterol is one of the many risk factors that are associated with heart disease. Statins generally act quickly to reduce cholesterol but results vary from patient to patient.
History
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Introduced to the market in 1987, statins have become one of the most widely used medications to treat high cholesterol and controlling cholesterol is one main way to prevent heart disease.
How Statins Work
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In many patients, healthy diets and exercise is not enough to lower cholesterol. These patients may be put on statin therapy. Statins work by reducing the formation of artery-clogging plaque. They often reduce LDL or bad cholesterol by up to 50% and increase a patients HDL or good cholesterol by up to 15%.
Maximizing Statin Results
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The effectiveness of statins can be affected by patient lifestyle. Patients who make healthy lifestyle modifications can often see a reduction in their cholesterol as early as two weeks after starting statin therapy. A diet that is low in saturated fats and cholesterol slows down the formation of fatty plaque more quickly than a patient who continues a diet high in fats.
Statins and Heart Disease
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In combination with a healthy lifestyle, statins lower cholesterol levels and also reduce the risk of heart attack, stroke and other cardiovascular events.
Full Effects
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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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.
Dont Stop Taking Statins Without Talking To Your Doctor First
All drugs have side effects. Statins are no exception. Some people who take statins may notice side effects, including muscle pain and weakness. These side effects can be very uncomfortable, but you shouldnt stop taking your medicine because of them until you speak with your doctor.
Each statin is different, so your doctor may have you switch to a new medication to see if it reduces your side effects.
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Statins: What You Need To Know
What are statins? Statins are medications that are used to help lower cholesterol levels. But statins dont just help keep cholesterol levels in check, they also protect your heart.
Studies show that, for many people, these medications can:
- Protect against the stiffening or hardening of the arteries
- Prevent heart attacks and strokes
- Save lives
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.
For more information, check these frequently asked questions about statins.
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What Statins Are Available To Treat High Cholesterol
Available statin drugs
- Increased blood glucose levels.
- Reversible memory issues.
If youre unable to take statins because of the side effects, youre said to be statin-intolerant. If you are taking a statin, you should avoid grapefruit products because they can increase side effects. You should limit the amount of alcohol that you drink because combining alcohol and statin usage can increase your risk of liver damage. You may want to talk with your provider or pharmacist if you are concerned about any other types of interactions.
PCSK9 inhibitors
PCSK9 inhibitors are designed to attach to a particular liver protein, which results in lowered LDL cholesterol. This class of drug can be given with statins and is usually for people at high risk of heart disease who have not been able to lower their cholesterol enough through other means.
Dietary Factors That Tend To Elevate Ldl Cholesterol
Saturated Fat
Dietary saturated fat intake has been shown to increase LDL cholesterol. Saturated fats occur naturally in many foods dairy products, meat/seafood, and eggs contain both saturated fat and cholesterol. Dairy products are the leading source of saturated fat in Western diets. Avoidance of even low-fat dairy products is helpful for control of lipids, given that these cause small but significant increases in LDL.
Plant-based foods that contain saturated fats include coconut, coconut oil, coconut milk, and cocoa butter, as well as palm oil and palm kernel oil. Despite intense commercial promotion of some of these products, their effect on blood lipids is similar to that of animal-derived saturated fat. Coconut oil proponents try to argue that coconut oil has medium chain triglycerides which are shorter-chain saturated fats that arent as bad as the longer-chain saturated fats in meat and dairy. But you cant apply the MCT research to coconut oil. MCTs make up only about 10% of coconut oil. The majority of coconut oil is the LDL-raising longer-chain saturated fats, lauric and myristic.
Trans Fat
Unfiltered Coffee
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Pharmacokinetics And Drug Interactions
Statins have different pharmacokinetic properties which can explain clinically important differences in safety and drug interactions . Most statins are lipophilic except for pravastatin and rosuvastatin, which are hydrophilic. Lipophilic statins can enter cells more easily but the clinical significance of this difference is not clear. Most of the clearance of statins is via the liver and GI tract . Renal clearance of statins in general is low with atorvastatin having a very low renal clearance making this particular drug the statin of choice in patients with significant renal disease. The half-life of statins varies greatly with lovastatin, pravastatin, simvastatin, and fluvastatin having a short half-life while atorvastatin, rosuvastatin, and pitavastatin having a long half-life . In patientâs intolerant of statins, the use of a long-acting statin every other day or 2 times per week has been employed. Short acting statins are most effective when administered in the evening when HMG-CoA reductase activity is maximal while the efficacy of long-acting statins is equivalent whether given in the AM or PM . In patients who prefer to take their statin in the morning one should use a long-acting statin.
Thus, despite the excellent safety record of statins, careful attention must be paid to the potential drug-drug interactions. For additional information see Kellick et al .
Who Should Be Treated
In a sense, everyone. That’s because no cholesterol level is too good. But people with unhealthy levels should work hard to improve, while those with ideal results can afford to relax a bit. Table 1 shows the goals established by the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
Cholesterol is a crucial determinant of cardiovascular health, but it’s only one. In fact, smoking is even more dangerous than unhealthy cholesterol levels, and high blood pressure, diabetes, and lack of exercise are nearly as harmful. Because each risk factor adds to the harm of others, people with the most risk need the most vigorous treatment. Table 2 shows how an individual’s risk profile influences the choice of therapy.
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Can Statins Increase My Risk For Memory Loss Or Dementia
Memory and cognitive symptoms from statin use are very uncommon, and it is unclear if statins are really the culprit. When symptoms have been reported, theyre typically not severe and usually resolve when the statin dosage is adjusted or the medication is switched.Affected patients have reported feeling unfocused or fuzzy in their thinking, but these experiences are rare. Concerns about long-term cognitive problems and memory loss due to use of statins have not been proven. On the contrary, most recent data actually point to potential prevention of dementia due to statin use.These data are logical because one of the major causes of dementia is atherosclerosis, which is hardening of the arteries in the brain. There is strong evidence that statins protect against atherosclerosis. Its one of the invisible benefits of taking a statin medication.Also, keep in mind that increasingly high cholesterol and memory problems both are common symptoms of aging. Sometimes its difficult to disentangle these two, and thats why statin use and memory problems may seem related at times.If youre concerned about statins and memory loss, dont stop taking your medication without consulting your doctor. There may be other reasons for your memory symptoms, or alternate treatments for your high cholesterol can be considered.
Can Natural Remedies Lower High Cholesterol Without Statins
Exercise on its own doesnt lower your LDL much often only a few points. Exercise helps minimize many heart disease risk factors, including obesity and Type 2 diabetes. Make a point to exercise five days a week for at least 30 minutes each day.Diet is incredibly important in managing your cholesterol.Every patient who comes to our preventive cardiology clinic for cholesterol management sees a nutritionist as part of the visit because we feel so strongly about the importance of diet. There are many patients for whom weve delayed prescribing statins, or suggested that they get off their medication if it isnt appropriate for their level of risk.Some patients think, Im on a statin I dont have to exercise, and I can eat whatever I want! But thats not the case. Lifestyle choices absolutely matter. For high-risk patients, its not a question of either improving the diet or getting on a medication, its both lifestyle changes and taking a statin together are necessary to protect high-risk patients against heart attack and stroke.If your cholesterol is borderline but not yet high, changing your diet and incorporating healthier food choices can help lower your cholesterol a decent amount. Eating more fiber and lowering your intake of saturated fat definitely can help. For people with relatively low risk, this may be enough to lower heart attack and stroke risk.
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Understanding Your Cholesterol Results
The results of a cholesterol test can be as confusing as they are important. Learn the difference between LDL and HDL, and how to lower your cholesterol. What do my cholesterol results mean?
Thats because lowering heart attack risk is not just a matter of lowering cholesterol. There are many other factors that damage artery walls and increase the risk of a heart attack or stroke, including:
- High glucose levels
- High blood pressure