Before we dive into the statistics on statins, a brief explanation into the difference between relative and absolute risk reduction is needed. Researchers and pharmaceutical companies often use relative risk statistics to report the results of drug studies. For example, they might say “in this trial, statins reduced the risk of a heart attack by 30%”. But what they may not tell you is that the actual risk of having a heart attack went from 0.5% to 0.35%. In other words, before you took the drug you had a 1 in 200 chance of having a heart attack; after taking the drug you have a 1 in 285 chance of having a heart attack. That’s not nearly as impressive as using the 30% relative risk number, but it provides a more accurate picture of what the actual, or “absolute” risk reduction is.
With that in mind, a closer look at the efficacy of statins can be examined in two broad groups of people: those with pre-existing heart disease, and those without. In the medical literature, these groups are referred to as “secondary prevention” and “primary prevention”, respectively. Secondary prevention (those with pre-existing heart disease).There’s little doubt that statins are effective in reducing heart attacks and deaths from heart disease in people who already have heart disease. Several large controlled trials including 4S, CARE, LIPID, HPS, TNT, MIRACL, PROV-IT and A to Z have shown relative risk reductions between 7% on the low end in MIRACL and 32% on the high end in 4S, with an average risk reduction of about 20%.
However, absolute risk reductions are much more modest. They range from 0.8% in MIRACL on the low end to 9% in 4S on the high end, with an average of 3%.
An analysis by Dr. David Newman in 2010 (published again in the Lancet in 2012: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960367-5/abstract
which drew on large meta-analyses of statins found that among those with pre-existing heart disease that took statins for 5 years:
- 96% saw no benefit at all
- 1.2% (1 in 83) had their lifespan extended (were saved from a fatal heart attack)
- 2.6% (1 in 39) were helped by preventing a repeat heart attack
- 0.8% (1 in 125) were helped by preventing a stroke
- 0.6% (1 in 167) were harmed by developing diabetes
- 10% (1 in 10) were harmed by muscle damage
A heart attack or stroke can have a significant negative impact on quality of life, so any intervention that can decrease the risk of such an event should be given serious consideration. But even in the population for which statins are most effective—those with pre-existing heart disease—83 people have to be treated to extend one life, and 39 people have to be treated to prevent a repeat heart attack. Moreover, these results do not apply to all populations across the board. Most studies have shown that while statins do reduce cardiovascular disease (CVD) events and deaths from CVD in women, they do not reduce the risk of death from all causes (total mortality). Nor do these results apply to men or women over the age of 80. Statins do reduce the risk of heart attack and other CVD events in men over the age of 80, and especially at this age, these events can have a significant negative impact on quality of life. However, the bulk of the evidence suggests that statins don’t extend life in people over 80 years of age, regardless of whether they have heart disease, and the highest death rates in people over 80 are associated with the lowest cholesterol levels.
Primary prevention (those without pre-existing heart disease)
Statins do reduce the risk of cardiovascular events in people without pre-existing heart disease. However, this effect is more modest than most people assume. Dr. Newman also analysed the effect of statins given to people with no known heart disease for 5 years:
- 98% saw no benefit at all
- 1.6% (1 in 60) were helped by preventing a heart attack
- 0.4% (1 in 268) were helped by preventing a stroke
- 1.5% (1 in 67) were harmed by developing diabetes
- 10% (1 in 10) were harmed by muscle damage
In addition, while statins do moderately reduce cardiovascular events such as heart attack in people without heart disease, they have never been shown to extend lifespan in this population. This is true even when the risk of heart disease is high. In a large meta-analysis of 11 randomized controlled trials published in the Archives of Internal Medicine, statins were not associated with a significant reduction in the risk of death from all causes.
This trial included 65,000 people without pre-existing heart disease but with intermediate to high risk of heart disease. It was important because it was the first review that only included participants without known heart disease. Previous studies suggesting that statins are effective in reducing death in people without pre-existing heart disease included some people that did have heart disease, which would have skewed the results.
The lack of significant effect on mortality is even more interesting in light of the fact that LDL cholesterol levels did decrease significantly in the statin group; the average LDL level in those taking placebo was 134 mg/dL and the average in the statin-treated patients was 94 mg/dL—roughly 30% lower. Yet in spite of this marked reduction in LDL cholesterol in the statin group, there was no difference in lifespan between the two groups. This is yet another line of evidence suggesting that the amount of cholesterol in LDL particles is not the driving factor in heart disease.
A meta-analysis of statin trials in people without heart disease by the prestigious Cochrane Collaboration came to a similar conclusion. They also observed that all but one of the clinical trials providing evidence on this issue were sponsored by the pharmaceutical industry. This is significant because research clearly indicates that industry-sponsored trials are more likely than non-industry-sponsored trials to report favourable results for drugs because of biased reporting, biased interpretation, or both.
Adverse effects of statins
If statins were harmless and free, then it wouldn’t matter how many people need to be treated to prevent a heart attack or extend someone’s lifespan. But statins are not free, nor are they harmless. Statin use has been associated with a wide range of side effects, including myopathy (muscle pain), liver damage, cataracts, kidney failure, cognitive impairment, impotence and diabetes.
Unfortunately, studies show that doctors are more likely to deny than affirm the possibility of statin side effects, even for symptoms with strong evidence in the scientific literature. Assuming that doctors would likely not report the adverse reaction in these circumstances, it’s probable that the incidence of
statin side effects is much higher than the reported rates.
One of the most troubling side effects of statins that has only recently become apparent is their potential to increase the risk of diabetes, especially in women. A study by Dr. Naveed Sattar and colleagues published in The Lancet in 2010 examined 13 randomized clinical trials involving over 90,000 patients taking statins. They found that statin use was associated with a 9% increased risk in developing diabetes. Note that this is a relative risk, so the absolute risk of developing diabetes while taking a statin is very low. That said, observational data from the Women’s Health Initiative found a 48% increased risk of diabetes in healthy women taking statins after adjusting for other risk factors.
The only population that statins extend life in are men under 80 years of age with pre-existing heart disease. In men under 80 without pre-existing heart disease, men over 80 with or without heart disease, and women of any age with or without heart disease, statins have not been shown to extend lifespan.
Statins do reduce the risk of cardiovascular events in all populations. A heart attack or stroke can have a significant, negative impact on quality of life—particularly in the elderly—so this benefit should not be discounted. However, the reductions in cardiovascular events are often more modest than most assume; 60 people with high cholesterol but no heart disease would need to be treated for 5 years to prevent a single heart attack, and 268 people would need to be treated for 5 years to prevent a single stroke. Statins have been shown to cause a number of side effects, such as muscle pain and cognitive problems, and they are probably more common than currently estimated due to under-reporting.
The intention here is not to suggest that statins have no place in the treatment of heart disease, but rather to give the objective information needed to decide (along with the doctor) whether they are appropriate for the individual in question. The decision whether to take them should be based on whether there is pre-existing heart disease, what the overall risk of a heart attack is, how healthy the diet and lifestyle is, what other treatments have been attempted, and individual risk tolerance and world view. It’s clear that statins reduce heart disease as well as the risk of death in those that have already had a heart attack, so if you’re in this group and you have already tried diet and lifestyle interventions without much impact on your lipid or inflammatory markers, you are more likely to benefit.