Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease ( CHD ) and other major vascular events in a wide range of individuals.
But each separate trial has limited power to assess particular outcomes or particular categories of participant.
A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done.
The meta-analysis was carried out by Colin Baigent and colleagues from the Clinical Trial Service Unit (CTSU) at Oxford University and Anthony Keech and colleagues from the NHMRC Clinical Trials Centre (CTC) in Sydney.
During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer.
Mean LDL cholesterol differences at 1 year ranged from 0·35 mmol/L to 1·77 mmol/L ( mean 1·09 ) in these trials.
There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol ( rate ratio [RR] 0·88; p<0·0001 ).
This reflected a 19% reduction in coronary mortality ( 0·81; p<0·0001 ), and non-significant reductions in non-coronary vascular mortality ( 0·93; p=0·2 ) and non-vascular mortality ( 0·95; p=0·1).
There were corresponding reductions in myocardial infarction or coronary death ( 0·77; p<0·0001 ), in the need for coronary revascularisation ( 0·76; p<0·0001 ), in fatal or non-fatal stroke ( 0·83; p<0·0001 ), and, combining these, of 21% in any such major vascular event ( 0·79; p<0·0001 ).
These benefits were significant within the first year, but were greater in subsequent years.
Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer.
Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics.
Baigent stated: “ The absolute benefits increased with continuing treatment and treatment produced a clear reduction in all-cause mortality. There was no evidence that lowering LDL cholesterol by 1 mmol/L with 5 years of statin therapy increased the risk of any specific cancer.”
“ Full compliance with available statin regimens can reduce LDL cholesterol by at least 1·5 mmol/L in many circumstances, and hence might be expected to reduce the incidence of major vascular events by about one third. Ensuring that patients at high 5-year risk of any type of occlusive major vascular event achieve and maintain a substantial reduction in LDL cholesterol would result in major clinical and public-health benefits," Keech said.
Source: The Lancet, 2005