HEALTH NEWS

Study Title:

Continued Evidence of Extensive Statin Damage to Human Health

Study Abstract

Objective To quantify the unintended effects of statins according to type, dose, and duration of use.
Design Prospective open cohort study using routinely collected data.

Setting 368 general practices in England and Wales supplying data to the QResearch database.

Participants 2 004 692 patients aged 30-84 years of whom 225 922 (10.7%) were new users of statins: 159 790 (70.7%) were prescribed simvastatin, 50 328 (22.3%) atorvastatin, 8103 (3.6%) pravastatin, 4497 (1.9%) rosuvastatin, and 3204 (1.4%) fluvastatin.

Methods Cox proportional hazards models were used to estimate effects of statin type, dose, and duration of use. The number needed to treat (NNT) or number needed to harm (NNH) was calculated and numbers of additional or fewer cases estimated for 10 000 treated patients.

Main outcome measure First recorded occurrence of cardiovascular disease, moderate or serious myopathic events, moderate or serious liver dysfunction, acute renal failure, venous thromboembolism, Parkinson’s disease, dementia, rheumatoid arthritis, cataract, osteoporotic fracture, gastric cancer, oesophageal cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.

Results Individual statins were not significantly associated with risk of Parkinson’s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer. Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract. Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin. A dose-response effect was apparent for acute renal failure and liver dysfunction. All increased risks persisted during treatment and were highest in the first year. After stopping treatment the risk of cataract returned to normal within a year in men and women. Risk of oesophageal cancer returned to normal within a year in women and within 1-3 years in men. Risk of acute renal failure returned to normal within 1-3 years in men and women, and liver dysfunction within 1-3 years in women and from three years in men. Based on the 20% threshold for cardiovascular risk, for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 (95% confidence interval 27 to 64) and for oesophageal cancer was 1266 (850 to 3460) and for men the respective values were 33 (24 to 57) and 1082 (711 to 2807). In women the NNH for an additional case of acute renal failure over five years was 434 (284 to 783), of moderate or severe myopathy was 259 (186 to 375), of moderate or severe liver dysfunction was 136 (109 to 175), and of cataract was 33 (28 to 38). Overall, the NNHs and NNTs for men were similar to those for women, except for myopathy where the NNH was 91 (74 to 112).

Conclusions Claims of unintended benefits of statins, except for oesophageal cancer, remain unsubstantiated, although potential adverse effects at population level were confirmed and quantified. Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely.

From press release:

The type and dosage of statin drugs given to patients to treat heart disease should be proactively monitored as they can have unintended adverse effects, concludes a new study on the British Medical Journal website.

Researchers at The University of Nottingham found that some statins can lead to an increased risk of liver dysfunction, acute renal failure, myopathy and cataracts in patients.

Cardiovascular disease is a leading cause of premature death and a major cause of disability in the UK. The use of statins is often recommended to reduce the risk of cardiovascular disease among high risk patients.Julia Hippisley-Cox, professor of clinical epidemiology and general practice, and Carol Coupland, associate professor in medical statistics, both at The University of Nottingham, wanted to measure the unintended effects of statins on certain clinical outcomes, taking into account the type, dose and duration of use.

They studied data collected from 368 general practices contributing to the QResearch database on 2,004,692 patients aged 30-84 years including 225,922 patients who were new statin users and prescribed a range of statins. The patients' adverse outcomes were studied from January 2002 to June 2008.

The researchers estimated the effects of type, dose and duration of statin use on clinical outcomes that have been associated previously with statins and then calculated the numbers needed to treat and harm.

They found there was no significant association between use of individual statins and risk of Parkinson's disease, rheumatoid arthritis, venous thrombo-embolism, dementia, osteoporotic fracture, or many cancers including gastric, colon, lung, renal, breast or prostate. There was a reduced risk associated with statin use for oesophageal cancer.

There was, however, an increased risk associated with using statins for moderate or serious liver dysfunction, acute renal failure, moderate to serious myopathy and cataracts and evidence of a dose response for acute renal failure and liver dysfunction with higher doses being associated with greater risk.

Adverse effects were similar for all of the different statins taken except for liver dysfunction, where the highest risks were found for fluvastatin. All of the increased risks persisted during the treatment, but were highest in the first year.

Overall, for every 10,000 high risk women treated with statins, there would be approximately 271 fewer cases of cardiovascular disease, 8 fewer cases of oesophageal cancer; 74 extra patients who experience liver dysfunction; 23 extra patients with acute renal failure, 307 extra patients with cataracts, and 39 extra patients with myopathy. Similar figures were found for men except rates of myopathy were higher. Some of the effects might be due to better detection rates since patients taking statins will consult their doctor more.

The authors said: "At national level, our study is likely to be useful for policy and planning purposes. Our study may also be useful for informing guidelines on the type and dose of statins."

A companion paper by the same researchers, published May 27 in the journal Heart, shows that their newly-developed and validated risk prediction algorithms could be used to identify patients at high risk of adverse events from statins so that they can be monitored more closely. A web calculator suitable for use by doctors can be found at www.qintervention.org

In an accompanying editorial, two senior cardiologists say that, like any intervention in medicine, statins are not entirely free of adverse events, but that when used according to current guidelines, the benefits outweigh the risks.

Study Information

1.J. Hippisley-Cox, C. Coupland.
Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database.
BMJ
2010 May
Division of Primary Care, University Park, Nottingham.