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Statin side effects examined

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“GPs should think more carefully about prescribing cholesterol-busting drugs,” reported BBC News, adding that some statin drugs raised the risk of adverse effects such as liver and kidney problems.

The research used medical records on over 2 million patients to assess side effects of cholesterol-lowering statin drugs. Clinical trials to approve a drug tend to look at side effects in a selected population over a relatively short time. This study monitored patients in general practice over a longer period of time, which allows rarer side effects to be revealed.

The study confirmed some side effects that are already known, such as an increased risk of muscle weakness, cataracts, acute kidney failure, and moderate or severe liver dysfunction. However, these problems were still estimated to be quite rare, with cataracts affecting less than 3% of statin users and other side effects less than 1%. A greater number of patients benefited from taking statins to lower cholesterol, which in turn prevented heart attacks. This study provides invaluable numerical data for clinicians that will help them weigh up the risks and benefits of these drugs for each patient.

Where did the story come from?

The study was carried out by researchers from Nottingham University, who received no external funding. The study was published in the peer-reviewedBritish Medical Journal.

The research was covered appropriately by national newspapers, which all included a pertinent quote from the British Heart Foundation: “A small number experience side-effects but the benefits far outweigh the risks.” However, some stories do not make it explicit that the overall risk of side effects remains quite small among statin users.

What kind of research was this?

Statins are cholesterol-lowering drugs that are prescribed to reduce the risk of heart disease among high-risk patients. The researchers say that statins are among the most widely prescribed medicines and that their use is likely to increase.

This was a prospective cohort study that investigated side effects of statins. Clinical trials of drugs tend to assess side effects of drugs over the short term, typically about five years. This type of study is appropriate for looking at potential long-term side effects in a large, unselected population.

What did the research involve?

The researchers used data from the general practice research database for England and Wales, which contains anonymous patient information on prescriptions and medical history contributed by GPs.

The researchers selected a cohort of patients (both users and non-users of statins) aged 30 to 84 years that were registered at GP practices between January 2002 and June 2008. Patients entered the cohort either 12 months after they had first registered with the GP or when they were prescribed statins for the first time.

Statin use was classified by the type of statin first prescribed and the starting dose. In total, approximately 2 million patients’ medical records were analysed from across 368 GP practices.

The researchers looked for moderate or serious myopathy (muscle weakness or pain) and defined this in the study as a diagnosis of myopathy or rhabdomyolysis (a type of muscle breakdown). In the event of diagnosis of myopathy or rhabdomyolysis, treatment is likely to be discontinued. Diagnoses were made by the GP or through a blood test showing four abnormal levels of an enzyme called creatine kinase.

What were the basic results?

At study entry, 1,778,770 (83.8%) had not been prescribed statins, 9,513 (0.5%) were past users, 107,581(5.1%) were current users and 225,922(10.7%) were first users.

Simvastatin was the most commonly prescribed statin, with 70.7% of new users being prescribed this drug).

Compared to non-users, new users were more likely to be men, to be older and to have conditions such as atrial fibrillation, heart disease, vascular disease, high blood pressure, diabetes and kidney disease. The researchers found that the outcomes that were significantly associated with statin use were myopathy (muscle weakness or pain), cataracts, kidney failure, and moderate or severe liver dysfunction.

Out of the cohort, 15,020 had moderate or serious liver dysfunction. Statin use increased the risk of liver dysfunction approximately two fold in both men and women, with the highest risk associated with fluvastatin. Female hazard ratio (HR) of 2.53 (95% CI 1.84 to 3.47), male hazard ratio (HR) of 1.97 (95% CI 1.43 to 2.72).

The risk of liver dysfunction was associated with the size of fluvastatin dose. The risk across all statins was highest in the first year of statin use. After stopping statins the risk decreased to that of a non-user within one to three years in women and after three years in men.

Out of the total cohort, 1,406 developed moderate or severe myopathy. Statins increased the risk of myopathy approximately three to seven fold, although the risk did not vary by type of statin. The risk was highest in the first year of taking statins, although the risk persisted after stopping treatment.

Out of the whole cohort of statin users and non-users 36,541 individuals developed cataracts, with the risk of cataracts being between 1.25 and 1.56 times greater among statin users than among non-users. There were no differences in risk for the different types of statin. The risk returned to normal within the first year of stopping treatment.

There were 1,969 cases of kidney dysfunction. The risks associated with statins ranged from 50% increased risk to a 100% increased risk (i.e. double). The risk remained during the first year of stopping treatment, but returned to normal one to three years after stopping treatment.

Alongside these side effects the researchers found that statins actually lowered the risk of oesophageal (throat) cancer in both men prescribed simvastatin (HR 0.69, 95% CI 0.50 to 0.94) and women prescribed simvastatin (HR 0.82, 95% CI 0.68 to 0.99). Across the total cohort 1,809 people developed oesophageal cancer.

The researchers estimated that for every 10,000 women treated with statins there would be 271 fewer who developed cardiovascular disease and 301 fewer men for every 10,000 treated. However, for these 10,000 people there would be 17 extra cases of kidney problems, 252 cases of cataracts, 65 people with liver problems and 32 extra cases of myopathy.

How did the researchers interpret the results?

The researchers report that they were able to quantify adverse effects associated with statins, including myopathy, liver dysfunction, acute renal failure and cataracts. These seem to be ‘class effects’, meaning they are generally consistent across all types of statin rather than varying according to individual drugs. There was a ‘dose-response effect’ (larger doses had larger effects) for acute renal failure and liver dysfunction consistent with that reported elsewhere.

The researchers say that adverse effects tended to be similar across the types of statins for most outcomes except for liver dysfunction, where the highest risks were associated with fluvastatin.

Conclusion

This is a large and well-conducted study that has shown that there was an increased risk of myopathy (muscle weakness), cataracts, kidney failure, and moderate or severe liver dysfunction associated with statin use. However, very few in the study population (non-users and users of statins) developed the conditions, suggesting that it is important for people considering these drugs to have an understanding of their individual chances of any side effect when compared to the potential benefit. The study did show that fluvastatin gave the highest risks for liver dysfunction and this may affect the choice of which statin to prescribe.

This research has looked at the risks and benefits of statins and has provided useful estimates of the absolute risks (the estimated number of extra cases of side effects for every 10,000 patients treated). 

It should be remembered that the benefits of statins seem to outweigh the risk of side effects for most people. These estimates constitute invaluable numerical data for clinicians, helping them consider the likelihood of specific risks and benefits on a patient-by-patient basis. Members of the public should not alter their use of medication without appropriate medical guidance from a doctor or pharmacist, who can discuss any concerns they may have about statins.

Links to the headlines

Statins ‘raise chances of kidney failure and cataracts’. The Daily Telegraph, May 21 2010

Liver failure warning on statin drugs. Daily Mirror, May 21 2010

Statin side-effect risk uncovered. BBC News, May 21 2010

Statins: The side effects ‘are worse than feared’. Daily Mail, May 21 2010

Statins can be risk to health. Daily Express, May 21 2010

Links to the science

Hippisley-Cox J, and C Coupland. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 2010;340:c2197

  • 5 Comments

Readers' comments (5)

  • 75 percent of people who have heart attacks have a normal cholesterol level. Inflammation, not arterial plaque from cholesterol, seems to be the more serious villain. There are other effective alternatives to statins that don't have the side effects discussed in this article, but which equally don't make billions for the pharmaceutical companies. Like fish oils, for example. A study in the American Journal of Clinical Nutrition, July 2006, showed that fish oils are more effective than the statin drug Lipitor in positively affecting the levels of HDL ("good") cholesterol in obese and insulin-resistant men. The major benefits of fish oil appear to be a reduction in sudden death from cardiac arrhythmias. Omega-3 fatty acids also appear to reduce triglyceride levels, reduce blood pressure, and stabilize the blood clotting mechanisms. There are several pathways in which fish oil can potentially benefit the cardiovascular system. The evidence that omega-3 fatty acids benefits the heart is now irrefutable, yet it is statins that get all the publicity. They are the 'ideal' pharmaceutical product - they don't claim to cure, but they do claim to 'manage' the problem so you can just keep taking them for ever and ever. Very profitable! But surely, a supplement with no side effects at all is preferable.

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  • My father has been on statins for some years. He suffered various side effects which we assumed was age related as he is 76 years old eg

    - aching legs
    - dizziness
    - difficulty in walking
    - massive personality change
    - angry
    - very depressed
    - very difficult to live with

    My father had been very active prior to all this and played tennis twice a week and went on regular hikes. He had to give up playing tennis and at times found it difficult to walk more than 400 yards.

    He became a grumpy old man. After 52 years of marriage my mother felt she could not live with him any more.

    It was also a most unhappy experience for him. One day he even broke down in tears in the middle of lunch.

    Within three days of giving up taking the Simvastatins he was back to his old amiable self and can now walk six miles or so.

    My opinion as his daughter : At 76 years of age isn’t it better to be active and live say 5 years of good quality life than 10 years by himself, being miserable and not being able to exercise!

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  • i was told 5yrs ago i had high cholestrol,and perscribed statins by my doctor.there is no history of heart desease in my family and i am a smoker of 10 cigs a day.i was recently taken off them by another doctor at my surgery after suffering with muscle pains and diffulcuty in walking,my eye sight has suffered also,bad mood swings,constipation one min and next day the opposite.i was on statins for 4yrs before being taken off them.was referred to hospital were they say i have fibromyagia and ostio arthritis ,i myself think most of my problems have come from continuous use of these statins.the worst thing i ever did was taking them without looking into the drug first.

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  • Anonymous | 25-May-2010 8:50 pm

    a very well written and well informed comment. I just think its a shame and can be very damaging that as soon as a new piece of research concerning health hits the press everybody seems to take it as gospel and rushes to follow its prescriptions. the problem is that considerably later more rigorous research findings often reveal the risks. it seems that one should question very carefully products which are claimed to affect health positively or negatively, and especially their use for those in good health, and what they accept for use whether it is simple treatments they purchase themselves or prescribed treatments from those they consider an authority such as medical practitioners. it should be realised that everything ingested, injected, administered rectally or applied topically to the skin contains chemicals, not all are harmless, and even soaps, shampoos, skin cleansers and treatments, body lotions, household cleaning and other products, recycled paper (especially toilet paper), make up and all cosmetics fall into this category and some have been found to be toxic or carcinogenic and periodically products are withdrawn from the market, but sometimes not before many years and a very large number of people have used them.

    the more natural products used with fewer chemicals the less damaging to our health and to our environment.

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  • it is just amazing how gps can mess up peoples' lives by prescribing medicines from almost every group which have not been adequately proven to be safe. patients often have serious side-effects from these and are then prescribed further medication to alleviate these thus perpetuating a vicious circle which makes monitoring for these side-effects impossible. some elderly patients have up to 10 tablets or more a day and live out the rest of their lives in a stupor with all sorts of risks such as falls, etc., etc., etc.

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