Arguments for more extensive use of cholesterol-lowering statins to protect against coronary heart disease have been bolstered by long-term data from a landmark clinical trial with Bristol-Myers Squibb’s Pravachol (pravastatin).
Long-term follow-up of the West of Scotland Coronary Prevention Study showed that, for the 10-year period after the trial had ended, the risk of death from coronary heart disease (CHD) or non-fatal myocardial infarction (MI) was 8.6% in participants originally assigned to pravastatin and 10.3% in the original placebo group. Over the entire follow-up period of 15 years, the risk of death from CHD or non-fatal myocardial infarction was 11.8% in the pravastatin group and 15.5% in the placebo group.
Similar percentage reductions were seen in the combined rate of death from CHD and hospitalisation for coronary events in both the 10- and 15-year periods. This was despite the bulk of the study participants no longer being on statin therapy. Five years after the original trial ended, 38.7% of the original statin group and 35.2% of the placebo group were being treated with a statin.
The long-term follow-up also assuaged concerns that statins may push up the risk of cancer or other non-cardiovascular conditions. After 15 years there were no excess deaths from non-cardiovascular causes, nor any fatal or incident cancers, the researchers reported.
Results from the long-term follow-up of the West of Scotland Coronary Prevention Study were published in the New England Journal of Medicine. The original trial, published in 1995, was pivotal in expanding the benefits of statins from treatment to prevention. It enrolled 6,595 mean aged 45-64 years with no prior history of myocardial infarction and with low-density lipoprotein (LDL) cholesterol in the range of 4-6 mmol/l. Participants were randomised to pravastatin 40mg/day or placebo and were followed up for an average of 4.9 years. Over this period, pravastatin was found to cut the combined risk of fatal and non-fatal myocardial infarction by 31%, while the risk of cardiovascular death overall on pravastatin fell by 32%.
In the long-term follow-up, the researchers tracked rates of all deaths, hospitalisations and deaths due to coronary events and stroke, as well as incident cancers and deaths from cancers, in those trial participants who had survived beyond the original five-year period.
Given that pravastatin is now extensively genericised (the first generic version of Pravachol was approved in the key US market in April 2006), the long-term preventive benefits seen in the West of Scotland study clearly have implications for the use of statins as a low-cost public health strategy to ward off coronary heart disease.
In an editorial accompanying the study results, Dr Michaeil Domanski of the US National Heart, Lung and Blood Institute said the outcomes proved the benefits of statins were “durable over the long term”, although he was less certain how early people with elevated cholesterol should start on statin therapy.