Friday August 10 2012
Statins help protect against heart disease by lowering cholesterol levels
‘Heart benefits of statins outweigh diabetes risk’, The Daily Telegraph says.
Statins are a type of medication widely used to lower blood cholesterol levels. While statins have proved reasonably effective in preventing cardiovascular disease (CVD), concerns have been raised that they could be associated with an increased risk of type 2 diabetes.
The Telegraph’s story is based on a large, five-year study from the US that was seeking to clarify the ‘risk-benefit balance’ between:
- statin use
- reduced risk of CVD
- increased risk of type 2 diabetes
The key findings of the study were that:
- in people with no pre-existing risk factors for diabetes (such as obesity) statins decreased the risk of a major CVD outcome (such as a heart attack or a stroke) by 52%, but did not increase the risk of diabetes
- in people with one or more risk factors for diabetes, there was a 28% increase of diabetes, but this has to be balanced against a 39% decrease in a major CVD outcome
The researchers calculated that by treating the (roughly) 11,000 people in this trial who had risk factors for diabetes, 134 CVDs or deaths would be avoided for every 54 extra cases of diabetes caused.
The findings of this trial will need to be evaluated alongside other evidence, but do suggest the benefits of statins outweigh the potential risks.
Where did the story come from?
The study was carried out by researchers from the Center for Cardiovascular Disease Prevention and the Division of Cardiovascular Medicine at Brigham and Women’s Hospital, Harvard Medical School, USA, and was funded by the drug company AstraZeneca. The study was published in the peer-reviewed medical journal, The Lancet.
The Telegraph accurately reported the main findings of this study, but it may have been more useful to readers if it had provided the actual numbers of people who might benefit. This would help both health professionals and patients to make a more informed decision about whether the benefits of statins are worth the risk.
What kind of research was this?
This was a randomised controlled trial which aimed to look at the benefit of statins in reducing the risk of cardiovascular events, and look at whether they increased the risk of type 2 diabetes, compared to an inactive placebo drug. The study population were people with no history of cardiovascular disease events; that is, the study was looking at the use of statins for primary prevention of cardiovascular disease (use of statins in people who have already had a heart attack or stroke would be secondary prevention).
A randomised controlled trial is the best way of looking at the risks and benefits of any intervention compared to a comparator. This particular trial further benefits from being of a large size, and including a reasonable length of follow-up (five years).
What did the research involve?
The JUPITER (Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial included 17,802 men and women (average age 66 years) who were randomised to take either 20mg daily of rosuvastatin or an inactive placebo drug for five years.
All participants were healthy, without known heart disease or diabetes, although 65% did have one or more major risk factor for diabetes, including:
- metabolic syndrome (a combination of risk factors that increase risk of diabetes and other cardiovascular disease)
- body mass index (BMI) of 30 or higher (having a BMI of 30 or above is considered to be clinically obese)
- impaired fasting glucose and /or elevated glycated haemoglobin (a longer term measure of blood glucose control): the elevated levels suggest there are ‘warning signs’ that diabetes may develop in the future
Participants were followed over the course of the five years, and the main outcome of interest was a combined cardiovascular outcome, such as:
- any first events of heart attack
- admission to hospital for unstable angina (similar to a heart attack but without the typical features on blood tests and ECG – suggests that a cardiac artery was blocked but has cleared by itself and that the person may be at risk of full heart attack)
- arterial revascularisation (surgery to unblock an artery)
- death resulting from a cardiovascular cause
Other outcomes of interest were doctors' diagnosis of diabetes, or venous thromboembolism (blood clot in the veins).
The trial was double blind, meaning that neither participants nor researchers knew whether statin or placebo had been taken.
After exclusion of those who were found to have diabetes at study start or who had missing data, 17,603 (99%) were included in the analyses. People with one or more major risk factor for diabetes (11,508) and those without (6,095) were analysed separately.
What were the basic results?
Overall, in all participants of the trial there were 270 reports of diabetes in people randomised to take rosuvastatin compared to 216 in the placebo group – a risk increase of 25% (hazard ratio [HR] 1.25, 95% confidence interval (CI) 1.05 to 1.49). The average time from randomisation to diagnosis of diabetes was 84.3 weeks in the rosuvastatin group vs. 89.7 weeks in the placebo group: an acceleration of 5.4 weeks.
When analysed separately by group, for people with one or more risk factor for diabetes, statin treatment gave:
- a 39% reduced risk of any of the major cardiovascular outcomes of trial (HR 0.61, 95% CI 0.47 to 0.79)
- a 28% increased risk of diabetes (HR 1.28, 95% CI 1.07 to 1.54)
- no significant effect on risk of venous thromboembolism or all-cause death
People without diabetes risk factors had:
- a 52% reduced risk of any of the major cardiovascular outcomes of trial (HR 0.48, 95% CI 0.33 to 0.68)
- no significant effect on risk of diabetes, venous thromboembolism or all-cause death
The researchers calculated that if the number of people in this trial who had diabetes risk factors take a statin, then 134 cardiovascular events or deaths would be avoided for every 54 new cases of diabetes diagnosed. If the number of people in this trial without diabetes risk factors take a statin, 86 cardiovascular events or deaths would be avoided with no new cases of diabetes diagnosed.
How did the researchers interpret the results?
The researchers conclude from their trial that the cardiovascular benefits of taking a statin outweigh the risk of diabetes, even in people at high risk of diabetes.
This is a well conducted trial intending to weigh up the cardiovascular benefit against the diabetes risk of taking a statin. The large trial benefits from being double blind (neither participants nor researchers aware of study treatment) and including a reasonable length of follow-up.
Overall, the researchers find that amongst roughly 11,000 people with diabetes risk factors (such as metabolic syndrome or raised fasting glucose levels in the blood) 134 cardiovascular events or deaths would be avoided for every 54 extra cases of diabetes caused by taking a statin. Amongst roughly 6,000 people without diabetes risk factors who take a statin, 86 cardiovascular events or deaths would be avoided with no new cases of diabetes diagnosed.
These are important findings which add to the evidence on the benefit of statins for reducing cardiovascular events, and to the risk increase for diabetes.
It must be noted that the trial was examining the use of one statin for ‘primary prevention’ – that is, in people who have not suffered a cardiovascular event such as heart attack or stroke. It has not examined use of statins for secondary prevention in people who have already had a cardiovascular event, although the researchers say that in this group the diabetes risk is considered to be low compared with the reduced risk of having another cardiovascular event.
Also, the study has only examined one statin – rosuvastatin – though previous research has suggested that all statin drugs are associated with a similar small increased risk. The study has also only examined the medium dose of 20mg, and other research suggests that the risks may be dose-dependent and higher doses may be associated with higher risk.
When prescribing any drug its benefits and potential risks need to be taken into account. The findings of this trial will need to be evaluated alongside other evidence of the risks and benefits of statins at different doses and in different treatment groups. However, overall the findings confirm the net benefits of statins.
Analysis by NHS Choices. Follow Behind the Headlines on twitter.