Researchers urge caution in prescribing statins to healthy people – Dr Briffa

My blog on Monday focused on a piece published in the American Journal of Public Health which detailed some of the tactics drug companies use to persuade doctors to prescribe their wares. The conclusion? The more aggressively a drug is marketed to doctors, the more suspicious of it we should be, basically. I ended the blog with the following remark: “Applying the inverse benefits law should, I think, cause us to be particularly wary of cholesterol reducing drugs. Let us not be too surprised, then, that the science shows statin drugs to be not-very-effective at saving lives, while at the same time putting those who take them at risk of sometimes severe adverse effects.”

What I didn’t know when I wrote this is that a review of statin treatment was about to be published by the researchers from the Cochrane Collaboration [1]. This international collective of researchers prides itself of conducting systematic, unbiased reviews of treatments. The point of this review, the researchers claimed, was to assess the risks and benefits of statin treatment in what is known as the ‘primary prevention’ setting.

Here’s some context on this from a previous blog post:

Statin therapy broadly divides into two main approaches:

Primary prevention – where statins are given to essentially healthy people with no known cardiovascular disease (i.e. there is no evidence of arterial disease and no history of a heart attack and/or stroke)

Secondary prevention – where statins are given to people with known arterial disease and/or a history of heart attack and/or stroke

This distinction is important because individuals in the secondary prevention category are at generally high risk of further problems, and stand to benefit most from statin therapy. On the other hand, individuals in the primary prevention category are at generally low risk of cardiovascular disease issues (such as heart attack and stroke), and may therefore not benefit much from a strategy or treatment intended to prevent cardiovascular disease. This primary prevention category is particularly important when one considers that the vast majority of people taking statins are in this category, and if the pharmaceutical industry and some of its hired hands in the scientific and medical community have their way, increasing numbers of people will be taking statins in the future.

In the recent Cochrane review, 14 trials were analysed. They reported, having amassed the evidence, that overall risk of death was reduced by 17 per cent, and overall risk of fatal and non-fatal cardiovascular events such as heart attacks and strokes were reduced by 30 per cent. On face value, these results look pretty good. However, the devil turns out to be in the detail.

To begin with, the researchers allowed studies in which up to 10 per cent of participants were in the secondary prevention category. What this basically means is that their assessment of the data was not really focused on the primary prevention setting. What’s required is an analysis of purely primary prevention data. The Cochrane researchers did not manage this, but other researchers have. A meta-analysis of data from individuals in the primary prevention category published just last year [2] (reported here), no reduction in overall risk of death was found with statin therapy.

The Cochrane authors do mention this study, but it’s somewhat buried in the discussion. It is not mentioned at all in the introduction of their review in which they list more than one review, like theirs, that allowed secondary prevention data to corrupt the primary prevention data.

The Cochrane authors have also largely confined themselves to assessment of ‘relative risk’. However, it is well accepted that a more useful judge of the true effectiveness of a treatment is absolute risk reduction (if risk if low, relative reductions in risk translate to very small real reductions in risk) as well as ‘number need to treat’ (e.g. how many people need to be treated for one year to prevent one heart attack – generally, NNTs in primary prevention are high).

However, there are, I think, many good things about this Cochrane review. It highlights many of the deficiencies in the evidence-based regarding statin therapy. Here are a few highlights:

Of the 14 studies reviewed, four of them were not double-blind in design (double-blind studies, where neither the researchers not the participants know whether they are taking the active drug or placebo are considered the ‘gold standard’ for good clinical research).
11 of the 14 studies recruited individuals who, while perhaps not having a history of cardiovascular disease, nonetheless had what would traditionally be regarded as at least one major risk factor for cardiovascular disease such as raised blood fats, high blood pressure or diabetes.
2 major trials were stopped prematurely. This is as cause for concern as may lead to “an over-estimation of treatment effects…”
All but one of the studies was industry-funded. According to the authors, “It is now established that published pharmaceutical industry-sponsored trials are more likely than non-industry-funded trials to report results and conclusions that favour drug over placebo due to biased reporting and/or interpretation of trial results.”
The study participants were ostensibly white, male and middle-aged (average age 57), and the authors of the Cochrane review question the appropriateness of this data in, say, older individuals and women.
There was no evidence of significant adverse effects, though about half of the studies did not even report adverse effects. (For more on adverse effects, see the blog post I link to above).
There was little or no significant evidence on the cost-effectiveness of statins in primary prevention.
There was little or no significant evidence on the effects of statins on quality of life.

The authors conclude:

“This current systematic review highlights the shortcomings in the published trials and we recommend that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.”

While I have my reservations about this review, I do think it is high commendable that some researchers (at least) have a mind to review the data on statins with a degree of objectivity. While statins are vigorously promoted by many doctors and researchers, it is good to see some academics urging caution. It’s good that they are presenting the other side to statins. It’s a story that is rarely heard, but one that needs to be heard if individuals are going to make truly informed choices about whether they take a statin or not.

UPDATE:

After writing this post yesterday I got to talk about some of the issues the research raises on Channel 4 News here in the UK. Here’s the video…

References:

1. Taylor F, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub4.

2. Ray KK, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65 229 participants. Arch Intern Med. 2010;170(12):1024-1031