This randomized study investigated the effects of cholesterol lowering therapy and antioxidant vitamins in people at high risk of coronary heart disease (CHD). Just over 20,500 individuals who were deemed to be at high risk of CHD were recruited. Disease categories included coronary disease, other occlusive arterial disease, diabetes and hypertension. Patients with normal or even below average cholesterol levels were included in the study.
Individuals aged between 40 and 80 years were randomized to have either simvastatin 40mg daily or placebo for 5 years. In addition, half of each group received a vitamin cocktail (600mg E, 250mg C, 20mg beta-carotene) or placebo daily.
- Recruitment - patients aged 40-80 with a history of occlusive arterial disease (previous heart attack or stroke, angina, coronary or non-coronary revascularisation) or diabetes were eligible provided their own doctors did not consider statin therapy clearly indicated. Between 1994 and 1997, 63,603 potentially eligible individuals were screened and 20,536 (5,082 women) were recruited in 69 hospitals around the UK. At entry to the study, 8,510 (41%) reported a previous myocardial infarction (most of whom were elderly, female or had “low” cholesterol levels) and 4,876 some other manifestation of CHD. Among the 7,150 with no history of CHD, 1,820 reported a previous stroke or transient ischaemic attack, 2,701 some other peripheral arterial disease, and 3,982 had diabetes (with overlap between these categories, such that 2912 had diabetes without CHD or other diagnosed arterial disease). There were 4,891 aged 65-69 at entry to the study and 5,806 aged 70-80 (of whom 1263 were aged 75-80). Average total cholesterol at entry was 5.9 mmol/l with levels <5.0 mmol/l in 4,072, and LDL cholesterol <3.0 mmol/l in 6,793
- Randomisation to simvastatin and compliance with treatment - using a factorial design, participants were also randomly allocated simvastatin 40mg daily or matching placebo for 5 years. On average during the study, 15% of participants allocated simvastatin stopped taking this therapy and 17% of those allocated placebo started taking it, giving about two-thirds of full compliance. This resulted in an average LDL cholesterol difference of 1.0mmol/l between those allocated to take simvastatin and those allocated placebo (which is about two-thirds of the effect of using 40mg daily simvastatin in this population)
The major findings were as follows:
- in high-risk patients, cholesterol lowering reduced the risk of myocardial infarction and strokes by at least one-third and reduced the need for interventions such as arterial surgery, angioplasty and amputations
- reductions of at least one-third in major vascular events applied in groups where benefit had previously been uncertain such as women, people aged over 70, younger age groups, stroke patients, people with total cholesterol levels below 5 mmol/l (200mg/dl) or LDL-C below 3mmol/l (120mg/dl)
- for the first time, it has been shown that significant risk reductions occur in patients with diabetes, peripheral vascular disease or stroke with or without a prior history of coronary heart disease
- there was a significant 12% reduction (p<0.001) in all-cause mortality
- there was no evidence that treatment with the vitamin treatments could prevent deaths, strokes, myocardial infarctions, or any vascular disease outcomes
Approximately 5 years of simvastatin treatment prevents myocardial infarctions, strokes or other major vascular events in:
- 100/1000 people who have previously had a myocardial infarction
- 80/1000 people with angina or evidence of CHD
- 70/1000 patients with previous stroke or other occlusive arterial disease
- 70/1000 patients with diabetes
Cholesterol lowering with simvastatin reduced the risk of being hospitalised with unstable angina, by 30 admissions per 1000 treated over 5 years.
Note that the proportional reduction in the rate of first major vascular events with simvastatin of about a quarter was similar (and statistically significant) in each subcategory of patient studied. It was seen even in those whose pre-treatment LDL-cholesterol measurement was below 3•0 mmol/l or total cholesterol was below 5•0 mmol/l, and among those with diabetes but no previous evidence of vascular disease. Moreover, these benefits were additional to the effects of other cardioprotective treatments, such as aspirin, beta-blockers and ACE-inhibitors.
- MRC/BHF Heart Protection Study: preliminary results.Int J Clin Pract 2002, Jan-Feb 56(1), 53-6.
- British Heart Foundation (7/2003). The Medical Research Council (MRC)/British Heart Foundation (BHF) Heart Protection Study