Simvastatin in the News
Do statins reduce Alzheimer's risk?
Statins: Are these cholesterol-lowering drugs right for you? Should you be on a statin?
Statin trial stopped after success.
Study expands on recent findings showing benefits for patients with low cholesterol.
Should even the healthy take statins?
Do statins reduce Alzheimer's risk?
The "first direct evidence" that statins - cholesterol-lowering drugs - can reduce your risk of developing Alzheimer's disease by 79% has been found, the Daily Mirror reported. Researchers discovered "fewer tangles" - a conclusive sign of Alzheimer's - in the brains of those who took the drug" the newspaper reported.The story was based on a study that looked at the brains of people after they had died, and compared the findings between people who had taken statins and people who had not. The study authors caution against generalising these findings to a living population. The study looked only at brain changes that are known to be typical of Alzheimer's disease, and not those that put people at risk of developing symptoms of Alzheimer's disease.
The study cannot establish whether taking statins directly prevented these changes in the brain, as it cannot establish which event came first, statin use or the brain changes. In addition, many other factors could play a role in the development of these changes. Further studies are needed before it can be said for certain whether statin use reduces the risk of Alzheimer's disease.
Where did the story come from? Gail Li and colleagues at the University of Washington and other research and health care institutes in Washington carried out this research. The study was funded by the National Institute on Aging in the US and was published in the peer-reviewed medical journal, Neurology.
What kind of scientific study was this? This cohort study looked at statin use in 110 people who had been enrolled in the large Adult Changes in Thought study between 1994 and 2002, and had since died. When they started the study, the people had been 65 years or above and had normal brain function; during the study, people were examined every two years to see whether they had developed Alzheimer's disease (AD).
After they died, the volunteer's brains were examined, to see if they showed the typical signs of Alzheimer's disease: plaques and tangles in the brain.
Researchers then looked back at prescription data to see which volunteers were statin users and which were not. Anyone who had received three or more prescriptions for 15 or more statin pills was considered to be a statin user. Researchers then compared how severe the plaques and tangles were in people who took statins and those who did not, using complex statistical methods. In these analyses they also took into account any differences in sex, brain function at baseline, age at death, brain weight, and the presence of small lesions in the brain.
What were the results of the study? The researchers found that people who took statins were less likely to have typical Alzheimer's disease like brain changes - plaques and tangles - than those who did not (the odds of having these changes were reduced by 79% - the number reported by the papers). When they looked at plaques and tangles separately, statin users were more likely to have less severe tangles, but not plaques, than people who did not take statins.
What interpretations did the researchers draw from these results? Researchers concluded that there is an association between statin use and tangles at post-mortem, one typical feature of Alzheimer's disease. They acknowledge that additional studies are needed to look at whether statins "may be" causing the reduction in the development of these tangles.
What does the NHS Knowledge Service make of this study? This was an interesting preliminary study, but it has several limitations, which the authors acknowledge:
As the researchers could only look at brain pathology after death, they cannot say for certain whether the tangles and plaques developed before the volunteers started taking statins or after. Without knowing which event came first, it is impossible to say whether statins caused these changes in brain pathology.
As volunteers were not randomly allocated to statin use or non-use, these groups may not have been balanced in terms of their characteristics. In fact, more statin users were male, they had more cardiovascular disease, were more likely to be smokers, and had lower cognitive function scores at the start of the study. Although the researchers tried to adjust for these factors, these or other factors may be responsible for the reduction in Alzheimer's disease pathology rather than statin use.
These findings relate to what the brain looks like after the volunteer has died. The authors do not report whether, in life, the volunteers had any symptoms of Alzheimer's disease, therefore we cannot say whether statin use was associated with symptoms in living volunteers.
Those who agreed to post-mortem examination were a small subset of those in the study and this means these people were not representative of the entire population enrolled being studied. They were more likely to be female, Caucasian, and older at death than other volunteers. Therefore these findings may not be applicable to the population as a whole.
In light of these facts, the authors of the paper state that "our findings should be extrapolated to living populations with the greatest caution, if at all".
Sir Muir Gray adds... This is reassuring evidence that makes it very unlikely that taking statins can increase the risk of Alzheimer's disease; whether they decrease the risk is a question that requires further research.
Statins: Are these cholesterol-lowering drugs right for you? Should you be on a statin?
These cholesterol-lowering drugs have benefits and risks. Find out whether your risk factors for heart disease make you a good candidate for statin therapy.Statins, drugs that are used to lower cholesterol, are being touted as one of the wonder drugs of the 21st century. They work by blocking a substance your body needs to make cholesterol. They may also help your body reabsorb cholesterol that has accumulated in plaques on your artery walls, helping prevent further blockage in your blood vessels. Statins include well-known medications such as atorvastatin (Lipitor), simvastatin (Zocor), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor) and others.
Already shown to be effective in lowering cholesterol, statins may have other potential benefits. But doctors are far from knowing everything about statins. Are they right for everybody with high cholesterol? What happens when you take a statin for decades? Can they help prevent other disease?
Here's some information to help you put information about statins into perspective as you weigh whether they're right for you.
Should I be on a statin?
Whether you need to be on a statin depends on your cholesterol level along with your other risk factors for cardiovascular disease. If you have high cholesterol, meaning your total cholesterol level is 240 milligrams per deciliter, or mg/dL, (6.22 millimoles per liter, or mmol/L) or higher, or your "bad" cholesterol (LDL) level is 130 mg/dL (3.68 mmol/L) or higher, the numbers alone won't tell you or your doctor the whole story.
High cholesterol is only one of a number of risk factors for heart attack and stroke. Before you're prescribed a statin, your cholesterol level is considered along with other factors including:
· Family history of high cholesterol or cardiovascular disease
· Lifestyle
· Blood pressure
· Age
· General health
· Presence of diabetes
· Excess weight
· Smoking
· Peripheral vascular disease — narrowing of the arteries in your neck, arms or legs
If the only risk factor you have is high cholesterol, you may not need medication because your risk of heart attack and stroke is probably already low.
If your doctor decides you should take a statin, you and your doctor will have to decide what dose to take. Statins come in varied doses — from as low as 5 milligrams to as much as 80 milligrams, depending on the medication. If you need to decrease your LDL cholesterol significantly — by 50 percent or more, it's likely you'll be prescribed a higher dose of statins. If your LDL cholesterol isn't as high, you'll likely need a lower dose. Talk to your doctor if you have concerns about the amount of statins you're taking.
Lifestyle is still key for lowering cholesterol.
Lifestyle changes are essential for reducing your risk of heart disease, whether you take a statin or not. Quitting smoking, eating a healthy diet, getting daily activity and managing stress are examples of lifestyle changes that will improve cholesterol, and most all of the other risk factors for heart disease. In fact, lifestyle changes may have a greater impact on reducing risk of heart disease and stroke than does medication alone.
If you're following the recommended lifestyle behaviors but your cholesterol — particularly your low-density lipoprotein (LDL), or "bad" cholesterol — remains high, statins might be an option for you. Risk factors for heart disease and stroke are:
· High cholesterol
· High blood pressure
· Diabetes
· Excess weight
· Family history of heart disease
· Physical inactivity
· Heavy alcohol use
· Poor stress and anger management
· Age
· Smoking
· Peripheral vascular disease — narrowing of the arteries in your neck, arms or legs
Consider statins a lifelong commitment.
You may think that once your cholesterol goes down, you can stop taking medication. But, if your cholesterol levels have decreased as a result of taking a statin, you'll likely need to stay on it indefinitely. If you stop taking it, your cholesterol levels will probably go back up.
The exception may be if you make significant changes to your diet or lose a lot of weight. Substantial lifestyle changes may allow you to maintain low cholesterol without continuing to take the medication, but do so under your doctor's supervision.
The side effects of statins
Although statins are well tolerated by most people, they do have side effects, some of which may go away as your body adjusts to the medication. Side effects include:
· Muscle and joint aches (most common)
· Nausea
· Diarrhea
· Constipation
There are two potentially serious side effects of statins of which you need to be aware:
· Liver damage.
Occasionally, statin use causes an increase in liver enzymes. If the increase is only mild, you can continue to take the drug. If the increase is severe, you may need to stop taking it, which usually reverses the problem. If left unchecked, increased liver enzymes can lead to permanent liver damage. Certain other cholesterol-lowering drugs, such as gemfibrozil (Lopid) and niacin, increase the risk of liver problems even more in people who take statins. Because liver problems may develop without symptoms, people who take statins have their liver function tested periodically.
· Muscle problems. Statins may cause muscle pain and tenderness (statin myopathy). The higher the dose of statin you take, the more likely you are to have muscle pains. In severe cases, muscle cells can break down (rhabdomyolysis) and release a protein called myoglobin into the bloodstream. Myoglobin can damage your kidneys. Certain drugs when taken with statins can increase the risk of rhabdomyolysis. These include gemfibrozil, erythromycin (Erythrocin), antifungal medications, nefazodone (Serzone), cyclosporine and niacin. If you take statins and have new muscle aching or tenderness, check with your doctor.
It's important to consider the effects of statins on other organs in your body, especially if you have health problems such as liver or kidney disease. Also, check out whether statins interact with any other prescription or over-the-counter drugs or supplements you take.
Keep in mind that when you begin to take a statin, you'll most likely be on it for the rest of your life. Side effects are often minor, but if you experience them, you may want to talk to your doctor about decreasing your dose or trying a different statin. Don't stop taking a statin without talking to your doctor first.
Are there other options?
Statins effectively reduce bad cholesterol (LDL). But, because of genetic differences, the type or dose of statin each person takes can vary. For example:
· If you are not able to lower your LDL to the desired goal using statin medication, your doctor may add ezetimibe (Zetia) to your treatment plan or switch to a combination ezetimibe and simvastatin medication (Vytorin). This combination will help drop your LDL level further, perhaps even another 15 percent to 20 percent. You may have heard reports that the combination medication of ezetimibe and simvastatin (together, these two medications are called Vytorin) is no more effective than taking simvastatin by itself. But, this small study didn't find any differences in death, hospitalization or heart attacks between the two medications. If you are on this combination medication, you should continue to take it unless your doctor tells you otherwise.
· If you have both high LDL and high triglycerides, you may benefit from combining the statin with niacin (Niaspan) or combining the statin with a fibric acid drug such as fenofibrate (TriCor) or gemfibrozil (Lopid). The risk of muscle problems is higher when these medications are paired, so to combat that risk, your dose of statins may be lowered to less than 20 mg.
· If you have just high triglycerides, use of niacin (Niaspan) is very effective. Fibric acid agents (TriCor and Lopid) are another option. Fish oil (omega-3 fatty acid) supplements (Lovaza) in 2- to 4-gram doses also can help.
· If your high-density lipoprotein (HDL) cholesterol is low, niacin might be the best choice to raise it. Fibric acids also are useful but less effective than niacin. Exercise and weight loss may help, as well.
· If your doctor recommends niacin in addition to a statin, you might want to discuss taking a medication that combines both niacin and a statin, such as Simcor or Advicor. These medications can reduce the number of pills you have to take. However, that may be the only benefit. Research studies haven't yet shown that the combination drugs lower cholesterol more than does taking niacin and a statin separately.
In some cases, one medication may simply not be effective and a different drug must be substituted. For other people, lifestyle changes may be all that are needed to lower cholesterol.
What else can statins do?
High cholesterol affects all arteries, not just those in the heart. Its negative effects permeate the body, so it's likely that the benefits of lowering cholesterol might have widespread health benefits as well.
One promising benefit of statins appears to be their anti-inflammatory properties, which help stabilize the lining of blood vessels. This has potentially far-reaching effects, from the brain and heart, to blood vessels and organs throughout the body.
In the heart, stabilizing the blood vessel linings would make plaques less likely to rupture, thereby reducing the chance of a heart attack. Statins also help relax blood vessels, lowering blood pressure. In addition, statins have blood-thinning effects, reducing the risk of blood clots. For these reasons, doctors are now beginning to prescribe statins before and after coronary artery bypass surgery or angioplasty, and following certain types of strokes.
Other benefits of statins could include:
· Prevention of arthritis and bone fractures. Statins might help protect against osteoporosis, arthritis and bone fractures, but more research is needed to confirm this benefit.
· Prevention of cancer. It's unclear whether statins might reduce your cancer risk. While some studies have suggested statins could reduce cancer risk, later studies haven't found a connection between statin use and reducing risk for breast, colon, prostate, respiratory, skin, or gastrointestinal cancers.
· Reduction in the risk of dementia and Alzheimer's disease. Statins might help keep your brain healthy, but more research is needed.
· Protection of the kidneys. Statins may help protect kidneys, through their effects on cholesterol and blood pressure and perhaps their ability to reduce inflammation.
Statins may also be helpful in controlling the body's immune system response after an organ transplant.
Weighing the risks and benefits of statins
When thinking about whether you should take statins for high cholesterol, ask yourself these questions:
· Do I have other risk factors for cardiovascular disease?
· Am I willing and able to make lifestyle changes to improve my health?
· Am I concerned about taking a pill everyday, perhaps for the rest of my life?
· Am I concerned about statins' side effects or interactions with other drugs?
It's important to take into account not only your medical reasons for a decision, but also your personal values and concerns. Talk to your doctor about your total risk of cardiovascular disease and discuss how your lifestyle and preferences play a role in your decision about taking medication for high cholesterol.
Statin trial stopped after success.
Nov 2008One of the largest trials of a cholesterol-lowering drug ever conducted has been halted early after dramatic reductions in illness and death were seen in treated patients.
The Jupiter trial investigated the effects of rosuvastatin on almost 18,000 patients with low to normal cholesterol levels but raised concentrations of an inflammation protein.
Under normal circumstances, the patients would not be considered at risk of suffering a heart attack, stroke, or dying from a heart-related cause. Yet those receiving medium doses of the drug, sold under the brand name Crestor, experienced far fewer adverse heart events than those given a non-active placebo.
Heart attack risk was reduced by 54% and stroke by 48%. The combined risk of heart attack, stroke and heart-related death fell by by 47%, as did the odds of undergoing surgical procedures. Because the benefits were so clear, an independent monitoring board halted the trial more than six months early last March.
Patients, recruited from 26 countries, were typically monitored for 1.9 years instead of three and a half as originally planned. All were apparently healthy, but all had high levels of C-reactive protein (CRP), an inflammation marker believed to be linked to heart disease.
A British arm of the study, led by Professor James Shepherd from the University of Glasgow, contributed more than 16% of the study participants. Writing in the New England Journal of Medicine, the researchers pointed out that recruiting patients with elevated CRP made a big difference to the results.
Previous statin trials have generally focused on elevated "bad" low-density lipoprotein (LDL) cholesterol. Their results led scientists conducting the new trial to expect a modest fall of about 25% in the number of adverse heart events.
But the effect they saw was much greater. The researchers, led by Dr Paul Ridker, from Harvard Medical School in Boston, US, reported: "The reduction in the hazard seen in our trial, in which enrolment was based on elevated high-sensitivity C-reactive protein levels rather than on elevated LDL cholesterol levels, was almost twice this magnitude and revealed a greater relative benefit than that found in most previous statin trials."
Rosuvastatin was "highly effective" at reducing levels both of cholesterol and C-reactive protein, said the researchers. The study highlighted the role inflammation played in heart and artery disease. The results were in a journal and were presented at the American Heart Association's Scientific Sessions meeting.
The trial was funded by the pharmaceutical company AstraZeneca, which manufactures Crestor. However, the company played no part in the data analysis or drafting of the paper, and did not have access to any results until the study was submitted for publication.
Study expands on recent findings showing benefits for patients with low cholesterol.
Millions more patients could benefit from taking statins, drugs typically used to prevent heart attacks and strokes, than current prescribing guidelines suggest, Johns Hopkins doctors report in a new study.Doctors have long known that statins can help prevent subsequent heart attacks and strokes in patients who have already had one of these cardiovascular events.
Additionally, statins have been shown to have a protective effect for patients who haven't yet had a heart attack or stroke but are at high risk for developing cardiovascular disease. Consequently, doctors currently prescribe these drugs both to patients with established cardiovascular disease, as well as those with high cholesterol and other risk factors for developing cardiovascular disease such as diabetes. About 33 million older adults — men age 50 or older and women age 60 or older — are currently eligible to take statins based on these criteria.
However, notes Erin D. Michos, M.D., M.H.S., assistant professor of medicine at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute, about half of all cardiovascular events occur in patients who don't have high cholesterol, and about 20 percent of these events occur in people who have no identifiable cardiovascular disease risk factor. Until recently, doctors haven't been sure if any of these patients might also benefit from statin therapy.
Last November, a research team led by doctors at Brigham and Women's Hospital in Boston announced the results of a study known as the JUPITER trial that involved nearly 18,000 patients.. They found that statins protect against heart attacks and strokes even in older adults without known cardiovascular disease or diabetes and with low cholesterol, below 130 mg/dl—a group that isn't usually prescribed statins—as long as these patients also had high levels of C-reactive protein (CRP), a blood marker for inflammation. Recent research has shown that inflammation plays an important role in initiating cardiovascular events, says Michos, but at-risk patients aren't routinely tested for CRP levels.
Building on the JUPITER trial results, Michos and Hopkins cardiology professor Roger S. Blumenthal, M.D., wondered how many patients in the United States fit the low-cholesterol, high-CRP profile featured in the study and might also benefit from taking statins. To get an estimate, they gathered data generated by the National Health and Nutrition Examination Survey, or NHANES. This research program, which has gathered various health data from thousands of Americans from 1971 to the present, weights the data from its participants so that they're representative of the entire United States population.
After searching NHANES between the years 1999 and 2004 for participants that fit the JUPITER profile, then extrapolating that to the general population, Michos and Blumenthal estimate that about 6.5 million older adults with low cholesterol and high CRP might benefit from statins. If they expanded their search criteria to the cholesterol level cutoff of 160 mg/dl that doctors often use when deciding to prescribe statins, the researchers increased this statin-benefiting group's size to 10 million.
"We're showing that doctors may be able to prevent thousands of heart attacks, strokes and deaths each year if we expand statin-prescribing criteria to include C-reactive protein levels, something we can assess as part of a simple blood test," says Michos.
The team points out in the study, published in the March 17 issue of the Journal of the American College of Cardiology, that based on JUPITER's results, prescribing statins to older adults using this new criteria that incorporates CRP would prevent about 260,000 cardiovascular events over five years.
Should even the healthy take statins?
The Times 11 April 2009For those with high cholesterol, Preventive medicine focuses on encouraging the general public to worry about illnesses that they will probably never develop, and on doctors to search for remedies that they may never need. But it saves lives. The number of British men and women dying prematurely from heart attacks has fallen by almost a third over the past decade and much of the credit must go to the increasingly widespread use of the statin family of cholesterol-lowering drugs.
Statins are taken by millions of people in the UK and are one of the key ingredients in the polypill (a collection of five different drugs being developed as a cardiovascular panacea for anyone over the age of 55). The Department of Health estimates that statins prevent about 10,000 early deaths every year, but a small and vocal group of sceptics believes that they are not as effective as claimed and that they cause a number of disabling side-effects.
The statin debate has particular resonance for me. Last week the NHS launched screening “MoTs” for men and women over the age of 40 in the hope of picking up a range of silent problems, such as raised cholesterol levels, and nipping them in the bud through lifestyle advice and medication. Sadly I wouldn't pass such an MoT because I have abnormal cholesterol levels caused by a glitch in my metabolism inherited from my parents - most worryingly high levels of cholesterol are caused by genes, not diet, and, even for those without a genetic defect, most of the cholesterol in their blood is made internally rather than consumed in animal-based foods in your diet.
I am a relatively clean-living, active, slim 46-year-old with normal blood pressure so there is not much that I can do to ameliorate my increased risk other than turn to pills - something that I have been recommending to many of my patients for years. So six months ago I decided to give statins a try and, while fully aware that one swallow doesn't make a summer, so far so good.
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There has been a string of articles in the press and on the internet suggesting that statins are largely peddled by overzealous doctors on the back of research that is riddled with vested commercial interest (the global market for statins runs into tens of billions of dollars, making them the most lucrative drugs in the world). But, while I encourage healthy cynicism, in recent years I have got off the fence and joined the majority of my colleagues in the pro-statin lobby.
My own experience of prescribing the drugs is that they are generally well tolerated. There are a number of recognised problems but, after trying out two of the most commonly used statins - atorvastatin and simvastatin - I can't say I have noticed any difference in how I feel. But there has been a dramatic improvement in my cholesterol profile.
Statins work by blocking the action of an enzyme in the liver that plays a key role in the internal manufacture of cholesterol. Taking a statin should lower cholesterol levels by about 20 to 30 per cent - three times the sort of drop that could be expected from switching to the healthiest of diets, and one that is likely to reduce the risk of heart attack and stroke by about a third.
This is a significant protective effect if you are a 55-year-old smoker recovering from your first heart attack (you are very likely to have another, and soon) but of negligible benefit if you are a clean-living 25-year-old marathon runner. Or, to put it another way, a third of a lot is worth having but a third of nothing is not - which is why doctors use risk calculators, rather than cholesterol levels per se, to determine who should be offered a statin (see box).
Although most of the protective effects of statins are attributed to a reduction in cholesterol, and to a slowing of the age-related furring of arteries that eventually leads to most strokes and heart attacks, that is not the whole story. They seem to work in other ways, too - probably by reducing inflammation of the lining of the arteries and stabilising deposits on the wall of the arteries so that they are less likely to tear or break off (the classic precipitating event for most heart attacks). And the benefits do not appear to stop there. Recent research suggests that people on statins are less likely to develop a range of other problems, including aggressive cancers of the prostate, Alzheimer's disease and dangerous blood clots (deep vein thrombosis or DVT).
I don't like having to take any type of medicine, but given the distinct improvement in my cholesterol profile and the lack of any noticeable side-effects, continuing on my statin would seem a no-brainer. What I do not know, of course, is whether hidden long-term effects will emerge once large numbers of patients have been taking the drugs for decades. But, as Winston Churchill was famous for pointing out, most of us spend our lives worrying about things that never happen.
Death, on the other hand, is a certainty - and in my case it is more likely to come from a stroke or heart attack than anything else. And while I cannot prevent the inevitable, statins may help me to delay it.
What are the risks?
Statins are generally well tolerated but can cause side-effects, and there is concern about long-term effects on the brain. Recent research has suggested their use may increase the risk of Parkinson's disease.
Common complaints include flatulence and an upset stomach, sleep disturbance and aching muscles. The latter should be reported to your GP because it can be a sign of potentially fatal reaction (rhabdomyolysis) thought to occur in fewer than one in 50,000 people taking the more popular types.
Long-term use can lead to inflammation of the liver. Some patients, particularly elderly people, complain of mental fogging and poor memory.
Statins deplete the body of the coenzyme Q10, and some doctors believe that Q10 supplements can reduce the likelihood of unwanted side-effects such as muscle pain.
There are no recommendations on dose, but 30mg-60mg daily would be a sensible minimum
