Substantial uncertainty had existed about the long-term benefits of cholesterol-lowering drug therapy for particular types of patient, and the extent of its use is limited. Uncertainty as to the possible benefits, or risks, of antioxidant vitamin supplementation was even greater.
To help resolve these uncertainties, the MRC/BHF Heart Protection Study was designed to be really large, to involve a substantial reduction in blood LDL cholesterol levels and a substantial increase in antioxidant vitamin levels, and to include a wide range of patients at substantial risk of death from heart disease and other causes. It provides reliable evidence about the effects of these cholesterol-lowering treatments and antioxidant vitamin supplements on mortality and major morbidity in a wide range of circumstances.
The Heart Protection Study (HPS) was a large UK, placebo-controlled, randomized trial of cholesterol-lowering with simvastatin 40mg daily versus placebo and of anti-oxidant vitamin supplementation, using a combination of vitamin C, vitamin E and beta carotene versus matching placebo. Between 1994 and 1997, 20,536 patients at increased risk of vascular disease were randomized in 69 hospital-based clinics around the UK. These patients were followed up for an average of 5 years in the study clinics while they continued on their randomized treatment, for a further 5 years by annual postal questionnaire and follow-up is on-going via electronic health records.
The HPS has shown that:
- Reduction in LDL-cholesterol with simvastatin 40mg daily reduced the risk of death by 13% (due to a reduction in death from vascular causes by 18% with no adverse effect on non-vascular causes) and of major vascular events (MVEs i.e. heart attacks, strokes or coronary or non-coronary revascularisation) by about one quarter in a wide range of different types of patient (including women, people with diabetes, and the elderly) among whom there was uncertainty about the benefits of cholesterol-lowering
- Supplementation with anti-oxidant vitamins is safe but does not reduce the risk of major vascular events
- Cholesterol-lowering with simvastatin 40mg daily was well tolerated, with no difference in the reports muscle pain between those on statin versus placebo and a small excess of myopathy (muscle symptoms with raised blood creatine kinase) of about 1 per 10,000 per year.
- Cholesterol-lowering with simvastatin 40mg is cost-effective in a variety of settings
- The effect of cholesterol-lowering for 5 years with simvastatin 40mg has no adverse effects over 11 years on cancer or other causes of mortality, and long term follow up of HPS participants continues
- The associations of major vascular events with a variety of plasma and genetic biomarkers have been investigated in the HPS data including CRP, BNP, KIF-6 and LpPLA2, and data from HPS has contributed to a number of meta-analyses of randomized trials and observational studies
The HPS database continues to provide valuable information on other risk factors, including Lp(a) and genetic factors. On-going investigations include looking at the long-term effects (over 10 years) of cholesterol-lowering and anti-oxidant vitamins on vascular and non-vascular events and cancers using data from electronic health records
The HPS trial was funded by the UK Medical Research Council, the British Heart Foundation and by Merck, who also provided simvastatin and matching placebo, and Roche who provided the anti-oxidant vitamin capsules and matching placebo. The long-term follow-up was funded by a grant from the British Heart Foundation and epidemiological studies have been funded by core grants to CTSU from the Medical Research Council, British Heart Foundation and Cancer Research UK.
Further information: http://www.hpsinfo.org/