Normally I write to you each Tuesday, but this week is an exception. The latest statin-related research findings are simply too important, I think, to wait until next week, which is why I’m getting this report to you today.
A new review study, published this week, assessed the evidence regarding the effectiveness and safety of statin drugs in essentially healthy people. This was a big story for anyone with an interest in cholesterol and drug therapy, and it culminated in me giving my take on the review and other pertinent cholesterol-related matters on Channel 4 news here in the UK (see video below).
The review in question was published by the researchers from the Cochrane Collaboration. 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. This essentially means giving statins to individuals who exhibit no evidence of arterial disease and have no history of a heart attack and/or stroke. In so-called ‘secondary prevention’, 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 potentially 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 was published just last year in the Archives of Internal Medicine .
This study was a meta-analysis (amassing of several similar studies) of 11 trials that included data on more than 65,000 people. An accompanying editorial  described this meta-analysis as “to date the cleanest and most complete meta-analysis of pharmacological lipid lowering for primary prevention.” Cleanest, because the reviewed studies included primary prevention individuals only. The reason why this is important is highlighted by the authors in the following passage: “Limiting the analysis to patients without existing coronary disease is critical because studies that include both groups of patients may appear to show benefit for all patients, when all the benefit accrues to those with existing disease.”
This huge and relevant study showed that statin use is NOT associated with a reduced risk of mortality in the primary prevention setting.
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, ‘numbers needed to treat’ 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-base 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).
- Eleven 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 high blood pressure or diabetes.
- Two major trials were stopped prematurely. This is a cause for concern as it may lead to “an over-estimation of treatment effects…” according to the authors of the Cochrane review.
- 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.
- 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 highly 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 a good thing that they are presenting the other side to statins because this is 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.
Next week, as promised, I’ll be exploring the evidence linking relatively low cholesterol levels with worse health outcomes, including an increased risk of death from cancer.
Here’s to a healthy heart
Dr John Briffa
for The Cholesterol Truth
Bear in mind all the material in this email alert is provided for information purposes only. We are not addressing anyone’s personal situation. Please consult with your own physician before acting on any recommendations contained herein.
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
3. Green LA. Cholesterol-Lowering Therapy for Primary Prevention – Still Much We Don’t Know. Arch Intern Med. 2010;170(12):1007-1008.