Statins are drugs that reduce cholesterol. They also reduce risk of heart disease and stroke. That does not mean, though, that they do they via their cholesterol-reducing effect. There are several lines of evidence which actually suggest otherwise. For example, statins can have clinical benefit before they reduce cholesterol levels. They also have been purported to reduce risk of heart events (like heart attack) in individuals who have ‘normal’ (non-elevated) cholesterol. And then we have the fact that cholesterol reduction through other means (other drugs, diet) has been shown to have no broad benefits for health (see here and here for more about this).
The fact the statins are unlikely to ‘work’ due their cholesterol-reducing effects is not a reason not to take then, however. It is a reason, however, to perhaps take the focus off cholesterol-reduction and put it on things that work better. And, of course even if statins do reduce the risk of cardiovascular disease, it at least makes sense to weigh up their risks and benefits over time.
A recent study in the British Medical Journal assessed the risks/benefits of statin therapy [1]. Here, in short, are the findings of this study:
For women, for every 10,000 high risk individuals treated with statins, there would be approximately 271 fewer cases of cardiovascular disease, 8 fewer cases of oesophageal cancer; 23 extra patients with acute renal [kidney] failure, 307 extra patients with cataracts; 74 extra patients who experience liver dysfunction; and 39 extra patients with myopathy [muscle pain and/or weakness].
For men, for every 10,000 high risk individuals treated with statins, there would be approximately 301 fewer cases of cardiovascular disease, 9 fewer cases of oesophageal cancer; 29 extra patients with acute renal failure, 191 extra patients with cataracts; 71 extra patients who experience liver dysfunction; and 110 extra patients with myopathy.
So, even in individuals at high risk of cardiovascular disease (i.e. those most likely to benefit from statin therapy), you have to treat lots of people with statins for one to benefit. But the reality is, more people will end up with a serious adverse effect as a result of treatment. Now, some would regard having a shot at preventing cardiovascular disease outweighs the other ‘less important’ risks. However, I suggest there are also those who would look at these statistics and reason that there really is little or no overall benefit to taking statins (and who could blame them). More about this later.
However, some will argue that it’s clear that statins benefits outweigh their harm on the basis that the reduce risk of death (overall mortality). Actually, there is an element of truth in this. However, it is important here to define better the sort of people who might take statins. 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.
OK, back to the evidence…
There is indeed evidence that in secondary prevention, statins have the ability to save lives. One meta-analysis (pumping together or similar studies), for instance, found that in people with know heart disease, statin therapy reduced risk of death by 16 per cent [2].
But what about the more numerous primary prevent people? Do statins reduce risk of death in this population? That was the question asked by a study published this week in the Archives of Internal Medicine [3]. This study was a meta-anlaysis of 11 trials that included data on more than 65,000 people. An accompanying editorial [4] 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 editorial also points out attention to the fact that in trials, individuals deemed to be at high risk of adverse effects, who take other medications and/or have other complicating illnesses are usually disallowed from taking part. However, this is not the case in the real world, where doctors commonly prescribe statins to more-or-less anyone with a raised cholesterol level (and increasingly, to people with normal cholesterol levels too). As a result, serious adverse effects may manifest that were not detected in the healthier trial subjects.
The editorial also highlights the fact that the trials are generally short (5-7 years), while use in the real world can go on for decades.
Some argue for statins on the basis that benefits are likely to accrue over time. But, this stance has no basis in science as, again, the editorial points out (we simply do not know one way or the other). The editorial authors also comment that the meta-anlaysis “…makes it clear that in the short term, for true primary prevention, the benefit, if any, is very small”.
I’m not against statins (though I would not take them myself). What I am against, however, is individuals given one-sided or misleading information about their risks and benefits. I’ve found in practice that once individuals are given a more complete picture about the effects of these drugs, the vast majority of people are happy not to take them.
References:
1. Hippisley-Cox J, et al. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database BMJ 2010;340:c2197
2. Wilt TJ, et al. Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern
Med 2004;164(13):1427-36
3. 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
4. Green LA. Cholesterol-Lowering Therapy for Primary Prevention – Still Much We Don’t Know. Arch Intern Med. 2010;170(12):1007-1008.
