Large-scale randomized controlled trials (RCTs) have well demonstrated the beneficial effects of
cholesterol-lowering treatment with
statins in patients at high risk of
vascular disease. However, large
statin RCTs were usually restricted to the typical 5-6 years. Moreover, non-cardiovascular events, especially the risk of
cancer, probably failed to emerge within a restricted period of 6 years. The aim of this study was to evaluate the long-term efficacy and safety of
statin treatment by performing a meta-analysis of
statin RCTs with extended follow-up beyond 6 years. Six RCTs with post-trial follow-up were eligible for inclusion, involving 47,296 patients with total follow-up ranging from 6.7 to 14.7 years. During the post-trial period, all the surviving participants were advised to take a
statin and the
cholesterol level were almost identical between the original
statin group and the original placebo group. Over the entire 6.7-14.7 years of follow-up, a significant reduction in the rates of all-cause mortality (relative risk 0.90, 95% confidence interval 0.85-0.96; P=0.0009), cardiovascular mortality (0.87, 0.81-0.93; P<0.0001) and major coronary events (0.79, 0.72-0.86; P<0.00001) was observed in favour of the original
statin group. During 2-year post-trial period, further reduction in all-cause mortality (0.83, 0.74-0.93; P=0.001), cardiovascular mortality (0.81, 0.69-0.95; P=0.01) and major coronary events (0.77, 0.63-0.95; P=0.01) was observed among initially
statin-treated patients. Over the entire follow-up period,
statin treatment did not increase the incidence of
cancers (0.99, 0.95-1.04; P=0.79), deaths from
cancers (1.00, 0.93-1.07; P=0.98) and non-cardiovascular mortality (0.95, 0.90-1.00; P=0.07). In conclusion,
statin treatment beyond 6 years is effective and safe in patients at high risk of vascular events. Moreover, earlier treatment with
statin may not only preserve the initial benefit but also have further survival benefit for additional 2 years. Further studies are called for to explore the underlying mechanisms.