Thursday May 17 2012
Should all over-50s take statins to prevent heart disease?
Everyone over the age of 50 should be given statins because the “cholesterol-busting” drugs reduce the risk of a heart attack even in healthy people, according to the Daily Telegraph and many other newspapers.
The story is based on a systematic review of 27 studies that looked at the effect of lowering “bad” cholesterol (low-density lipoprotein or LDL) using statin therapy in 175,000 people. It found that for every reduction in cholesterol of 1.0mmol/L, taking statins reduced the risk of heart attacks, strokes and other “major vascular events” by about a fifth (21%), even among people without vascular disease or who were at low risk of developing it.
Current guidelines recommend prescribing statins for people who have at least a 20% chance of developing cardiovascular disease within 10 years. Doctors normally calculate this risk by looking at a range of factors including the patient’s age, blood pressure, cholesterol levels, whether they smoke and whether they have diabetes.
This large review of studies suggests the cholesterol-lowering drugs are suitable for people who don't have heart or vascular disease and those who are not considered at high risk of developing it. The 21% reduction in risk of heart disease and stroke sounds impressive.
However, the number of people who stand to benefit from statins gets smaller as the risk threshold for treatment is reduced. For example, one thousand people at low risk would need to be treated (have a 1mmol/L reduction in bad cholesterol) for five years for 11 of them to benefit. This suggests that someone at low risk may wish to consider whether the possible benefit of taking statins would outweigh the inconvenience.
An editorial accompanying the review argues that the current guidelines should be revised so that age is used as an indicator for taking statins (over 50 years old), rather than using expensive screening tests. The commentary forms part of a running debate as to whether middle-aged people without any known risk of cardiovascular disease should be “medicated”, and, if so, how much (whether with statins, aspirin or a “polypill”, as previously suggested).
Where did the story come from?
The study was carried out by researchers from Oxford University and the University of Sydney. It was funded by several institutions including the British Heart Foundation, the UK Medical Research Council and Cancer Research UK. The study was published in the peer-reviewed medical journal The Lancet.
The study – in particular the commentary arguing for all over-50s to take statins – was covered widely and accurately in most of the media.
What kind of research was this?
This was a meta-analysis of individual patient data from 27 trials, which looked at the effects of lowering LDL cholesterol with statin therapy. It included trials of people without vascular disease or at low risk of cardiovascular disease.
The authors pointed out that their previous analysis of studies suggested that statin therapy to reduce LDL cholesterol in people without a history of vascular disease ultimately reduced their risk of heart attacks and strokes by about a fifth. However, uncertainty remains as to whether statins have an overall “net benefit” in this group, given that they are at low risk to begin with. The authors said that at least half of all heart attacks and strokes (vascular events) occur among individuals without previous disease.
The authors said they have now taken individual patient data from each trial within the database, allowing a more complete assessment of the effects of lowering LDL cholesterol in low-risk individuals.
What did the research involve?
The researchers conducted a meta-analysis of data from 175,000 participants in 27 randomised trials, to explore the effects of lowering LDL cholesterol with statin therapy. Trials were included if:
- they included at least one treatment where the main effect was to lower LDL cholesterol
- there were no other differences in treating risk factors
- at least 1,000 participants were recruited for a duration of at least two years’ treatment
The “major vascular events” the researchers looked at included heart attacks and deaths from heart attacks, strokes and coronary revascularisations (surgery to unblock coronary arteries). They also looked at rates of cancer and the cause of any death that occurred.
They grouped the participants into five categories depending on their risk of a vascular event within five years and compared those taking a statin with control groups or with group taking a lower-dose statin. The risk categories were:
- less than 5%
- 5% to less than 10%
- 10% to less than 20%
- 20% to less than 30%
- 30% or more
The researchers analysed the results using standard statistical methods.
What were the basic results?
The researchers found that:
- Reducing LDL cholesterol with a statin reduced the risk of major vascular events (relative risk [RR] 0.79, 95% confidence interval [CI] 0.77 to 0.81 per 1.0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular mortality and all-cause mortality.
- The reduction in major vascular events was at least as big in people in the two lowest risk categories as those in the higher risk categories.
- For strokes, the reduction in risk in participants with a five-year risk of major vascular events lower than 10% (RR per 1.0 mmol/L LDL cholesterol reduction 0.76, 99% CI 0.61 to 0.95) was also similar to that seen in higher-risk categories.
- In participants without a history of vascular disease, statins reduced the risks of deaths from vascular disease and any other cause (RR 0.91, 95% CI 0.85 to 0.97).
There was no evidence that reducing LDL cholesterol with a statin increased cancer incidence, death from cancer, or deaths from other non-vascular causes.
How did the researchers interpret the results?
The researchers calculated that in people with a five-year risk of major vascular events lower than 10%, each 1mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1,000 over five years. They said this benefit “greatly exceeds any known hazards of statin therapy”.
They also pointed out that, under present guidelines, such individuals would typically not be regarded as suitable for statin therapy.
They concluded: "The present report shows that statins are indeed both effective and safe for people with a five-year risk of major vascular events lower than 10% who would typically not be judged suitable for statin treatment … and, therefore, suggests that treatment guidelines might need to be reconsidered."
Current guidelines recommend statins for people who have a 20% or greater chance of developing cardiovascular disease within 10 years. This large review of studies, which further assessed previous research, suggests they may also benefit those without existing cardiovascular disease and those who are not considered at high risk of developing it. However, the individual benefit for those at low risk may be small.
Although the study looked at whether statins increased the risk of cancer and death from other causes, it did not include possible adverse effects. Statins are safe drugs that have been associated with a small risk of side effects. As the authors stated, the risk of side effects when giving statins to everyone over the age of 50 would have to be taken into account when calculating the overall benefit.
Current guidelines on statin therapy from the National Institute for Health and Clinical Excellence (NICE) will reportedly be updated soon, at which point NICE will take this and any other new evidence into account.
There is good existing evidence that a healthy lifestyle (including regular exercise, stopping smoking and a healthy diet) are important factors in cardiovascular health. This study helps answer previous uncertainty about whether apparently healthy individuals could benefit from taking statins.