Statins save lives in patients undiagnosed with heart disease

Given that February is National Heart Month (cue Valentine’s Day), I thought I would blog about a recent Cochrane review by the Cochrane Heart Group which has just been published, all about statins. Statins are a family of medicines prescribed for lowering cholesterol. They are one of the most commonly prescribed medicines, particularly by us cardiologists and our GP colleagues. The number of prescriptions and cost to the NHS of these drugs has grown significantly in the last few years, from £20 million in 1993 to £500 million in 2006. They are frequently prescribed for preventing further heart attacks and strokes when a patient has already had one (called secondary prevention by us doctors) but the evidence of benefit when given to patients to prevent a first heart or stroke (called primary prevention) is less clear. This review aimed to assess the effects, both harms and benefits, of statins in people with no history of cardiovascular disease.

What did they find?

The review included 56,934 participants in 19 trials. The average age of participants was 57, and range of ages from 28 to 97. Fourteen of the trials included patients with cardiovascular risk factors, such as raised cholesterol, diabetes and high blood pressure. Although the review was aimed at patients without evidence of cardiovascular disease, it did include trials where up to 10% of the study population did have a previous history of cardiovascular disease. This was presumably chosen to allow more trials and a larger population to be assessed, without compromising the essence of the review’s question. Statins assessed included pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin and simvastatin.

Death from any cause was reduced by 14%. Combined fatal and non-fatal cardiovascular disease was reduced by 25% and the combined numbers of coronary artery bypass operations and procedures to unblock coronary arteries (angioplasty) were reduced by 38%.

Only twelve of the studies reported on adverse events, with 19% of participants experiencing at least one. However, there was no significant difference between those taking statins and the control group, meaning if you were taking a dummy pill you were just as likely to report a problem with it as those taking the real statin pill. There was also no significant difference between the number of participants who stopped their treatment due to an adverse event between the statin and control groups. In subgroup analysis there was a very mild increase in risk of diabetes and liver enzyme elevations in the statin group.

How good was the evidence?

All trials were fully or partially funded by pharmaceutical companies, which is something to bear in mind. Research by Als-Nielsen and colleagues in 2003 demonstrated that pharmaceutical industry sponsored trials were more likely than non-industry funded trials to report results that favour the drug over placebo. A recent Cochrane methodology review confirmed these findings and investigated risks of bias associated with industry sponsorship in more detail. In the statins review 15 trials were double blinded (neither the patient nor the doctor knew whether the tablet was a statin or placebo), which is the recommended way to test a treatment fairly. The time that the patients were assessed in the trials ranged from one year up to 5.3 years. Overall, there was a low risk of bias and the authors of the review judged the quality of the trials to be good.

Comments

This review demonstrated a benefit in a population of adult patients, the vast majority of whom were without evidence of cardiovascular disease. However, the review included a very wide mix of patients, with ages ranging from 28 to 97, which make it more complex to apply these findings to an individual patient. To identify best which patients need treating, doctors often use risk charts and risk calculators, which with a few figures such as blood pressure, cholesterol, age and gender, can estimate a person’s risk of having a heart attack or stroke in the next five years. The authors report that treatment with a statin in people in the two lowest risk categories (<5% five-year risk, and 5% to 10% five-year risk, respectively) would avoid 6 and 15 major heart attacks or strokes, respectively, per 1000 people treated for five years. Or, in other words, if you treat 167 people with <5% five-year risk or 67 people with 5% to 10% five-year risk, you prevent one heart attack or stroke. It is always a difficult decision to take a tablet to prevent a disease you don’t yet have. What if you never get it and you’ve taken the tablet all your life? As with much of preventative medicine it comes down to balancing risk; is the risk of the treatment or the disease greater? The doctor should be a guide but it’s up to the patient to decide.

Please let me know your experience with statins, or if you are taking medicines to prevent a disease you do not have. How do you weigh up decisions for preventative medicines?

Harry will be writing more heart-related Evidently Cochrane blogs later this month.

Links:

Taylor F, Huffman MD, Macedo AF, Moore THM, Burke M, Davey Smith G, Ward K, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub5

Als-Nielsen B, Chen W, Gluud C, Kjaergard LL. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? JAMA 2003;290(7):921-8. PMID: 12928469

Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L. Industry sponsorship and research outcome. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: MR000033. DOI: 10.1002/14651858.MR000033.pub2
Podcast of the review: http://www.cochrane.org/podcasts/issue-10-12-october-december-2012/industry-sponsorship-leads-bias-outcomes-clinical-trials

Author:

Harry Boardman

Harry Boardman

Harry was with the UK Cochrane Centre from October 2012 – May 2013, where he undertook a fellowship in systematic reviews. He is currently part way through his Cardiology specialist training within the Oxford Deanery and before this undertook his medical training in London. He is interested evidence based medicine within cardiology, particular in relation to cardiovascular risk in women, imaging and devices.

You can follow Harry on Twitter @harry9bo

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3 thoughts on “Statins save lives in patients undiagnosed with heart disease

  1. Statins are also used in a condition called familial hypercholesterolemia which is one of the most common inherited metabolic diseases. We (Cystic Fibrosis & Genetic Disorders Group) have a review on statins for this condition in children. Traditionally, diet has been the main mode of treatment for young people with this condition, but since the 1990s trials have looked at using statins for these patients. The take-home message from the current version of the review is that treatment with statins seems to be efficient in lowering lipid levels in children with familial hypercholesterolemia; but while it seems to be safe in the short term, the limited duration of the included trials did not provide any evidence on long-term safety. Given that these children and young people will need to take these drugs all their lives, it seems vital that long-term trials are conducted to work out the potential long-term benefits and risks of statins.

  2. No long term trials of children or young people with FH are underway, if by long term you mean trials lasting the several decades it would take to count the number of cardiovascular events and deaths prevented by statins. Such trials will never be done — they just aren’t practical. In fact, no randomized controlled trials with clinical endpoints have been done in adult FH patients. When statins came on the market in the late 80s, FH patients were excluded from the statin trials because it was considered unethical to put an FH patient on a placebo. There was an imaging trial using carotid intima media thickness as an endpoint that showed a benefit for higher-dose statins over lower-dose statins in FH. There is also observational data from the British and Dutch FH registries that shows benefit.

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