updated October 2007
crabsallover highlights, key points, comments / links.
In the 1970s, scientists suspected that cholesterol was important in heart disease and that the higher the level of blood cholesterol, the higher the risk of heart disease. This led to the suggestion that, if cholesterol was lowered, the risk may be reduced. When cholesterol-lowering statin drugs became available in the next couple of decades, researchers decided that large studies, involving several thousands of patients, were needed to test them properly.
The biggest of these was the MRC-funded Heart Protection Study (HPS), a randomised and double-blind eight-year trial that was designed, coordinated and analysed by the Clinical Trial Service Unit in Oxford1. It began in 1987. As well as being the largest ever trial of cholesterol-lowering drugs, the HPS was the first to include a substantial number of women, elderly people, people with diabetes, and those with lower than average cholesterol. The trial used simvastatin (Zocor®), which was the first statin to become available in the UK; Merck & Co Inc helped fund the trial along with the MRC, the British Heart Foundation and Roche Vitamins Ltd.
Statins benefit everyone
To examine the effects of such drugs in detail, the investigators of all trials formed a group called the Cholesterol Treatment Trialists (CTT) Collaboration, also supported by the MRC. The group published a protocol in 1995 and agreed to look at all the results in a standard way. The first report from this group was published in 2005 in The Lancet, combining data from more than 90,000 participants2. It showed that, among people at increased risk, statins work quickly to reduce the risk of heart disease and stroke and the need for operations to restore blood flow in the arteries surrounding the heart. These benefits were similar, irrespective of a person’s initial cholesterol level.
For example, if someone has a cholesterol level of 6 millimoles per litre, which is high but not uncommon for a middle-aged person, a moderate dose of statin would lower it to 4.5 within weeks, with a maximum effect at between four and six weeks. For every one millimolar decrease in blood cholesterol concentration, the risk of heart disease and stroke decreases by about a quarter. About five years of statin treatment typically prevents major vascular events in 100 of every 1,000 people who have previously had a heart attack. Over the longer term, statins become even more effective. Serious side effects are extremely rare.
Treating people with statins leads to large savings – 22 per cent – in hospitalisation costs for all vascular events among a wide range of high-risk individuals. The drugs have substantially reduced in price after their patents expired in 2003 and now cost pence rather than pounds per day, which markedly increases their cost-effectiveness.
The HPS showed that a daily dose of statins is cost-effective for a wider range of people with vascular disease than was previously thought, but the analysis estimated cost-effectiveness during the study treatment period only3. The HPS team published a new model in the British Medical Journal in 2006, which extrapolated the HPS results to a wider spectrum of people and beyond the five-year treatment period4. They concluded that statin therapy should be considered routinely for more people at a lower risk of vascular events than previously thought.
The MRC team used the data from the 20,536 participants of the HPS and found that, at current generic prices, lifetime treatment with statins is cost-effective (costs less than £2,500 per life year gained) for people aged between 35 and 85 with risks of major heart attacks or strokes at one per cent a year.
The National Institute for Health and Clinical Excellence (Nice) published guidance at the beginning of 2006 saying that adults who have a 20 per cent or greater risk of developing heart disease over the next decade should be offered statins. Draft guidance in June 2007 stated that millions of people should be assessed to find out how many more would benefit from taking statins. A month later, Roger Boyle, the National Director for Heart Disease and Stroke, said that a ‘blanket approach’ to give everyone above a certain age a daily dose of statins would save lives, NHS funding and doctors’ time.
Based on the numbers of people with coronary heart disease, stroke and diabetes, the World Health Organization has estimated that if an extra 10 million high-risk people were to start statin treatment, this would save about 50,000 lives each year and would prevent similar numbers from suffering non-fatal heart attacks or strokes. Statins can benefit people even after they stop taking them – five years of treatment was associated with a significant reduction in coronary events for a subsequent ten years in men with high cholesterol who did not have a history of suffering from heart attacks5.
1. Heart Protection Study Collaborative Group (2002). MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial. The Lancet, 360, 7.
2. CTT collaborators (2005). Efficacy and safety of cholesterol-lowering treatment: prospective meta-analyis of data from 90 056 participants in 14 randomised trials of statins. The Lancet, DOI:10.1016/S0140-6736(05)67394-1.
3. Heart Protection Study Collaborative Group (2005). Cost-effectiveness of simvastain in people at different levels of vascular disease risk: economic analysis of a randomised trial in 20 536 individuals. The Lancet,365, 1779.
4. Heart Protection Study Collaborative Group (2006). Lifetime cost effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20 536 people. BMJ,DOI:10.1136/bmj.38993.731725.BE.
5. Ford et al. (2007). Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med, 357, 1543.
MRC, December 2006, updated October 2007