Long-term efficacy and safety of statin treatment beyond six years: a meta-analysis of randomized controlled trials with extended follow-up

Pharmacol Res. 2014 Mar;81:64-73. doi: 10.1016/j.phrs.2014.02.006. Epub 2014 Mar 3.


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.

Keywords: Atorvastatin (PubChem CID: 60823); Cancer; Cholesterol (PubChem CID: 5997); Fluvastatin (PubChem CID: 446155); Meta-analysis; Mortality; Pravastatin (PubChem CID: 54687); Safety; Simvastatin (PubChem CID: 54454); Statin.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / epidemiology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / epidemiology
  • Incidence
  • Mortality
  • Neoplasms / epidemiology*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors