Statins (HMG-CoA reductase inhibitors), are effective long term

Statins (HMG-CoA reductase inhibitors), a class of drugs that block production of cholesterol in the liver, lower total cholesterol and LDL and are also associated with cardiovascular benefits, are effective in the long term, conclude authors of a study in this week’s issue of THE LANCET.

Few data are available about the long-term effects of statins because previous trials have not extended beyond 5-6 years; however, the results of a Nordic study with a follow-up of 10 years has found that, in the long term, statins may decrease mortality rate and incidence of cancer.

The Scandinavian Simvastatin Survival Study (4S) led by Timo Strandberg (University of Helsinki, Finland) and colleagues was launched in 1989. Patients from five participating countries- Denmark, Finland, Iceland, Norway and Sweden-were randomly assigned to 5 years of statin therapy with simvastatin or allocated a placebo.

The results of the trial were published in THE LANCET 10 years ago (Lancet 1994; 344: 1383-89). 5-year follow-up showed that statins lowerd lipid fractions and cholesterol concentrations; furthermore, simvastatin treatment reduced cardiovascular mortality and coronary mortality by 36% and 43%, respectively. This trial was the first to demonstrate the advantage of lowering cholesterol in patients with coronary heart disease, and ushered in a revolution in treating heart disease more aggressively.

The long-term follow-up results compare the initial 2221 patients who have had simvastatin for 10 years, compared with the 2223 patients who initially received placebo (and only started statins 5 years ago after the 4S trial was completed and the results of statin benefit became known). Overall, there was a 17% reduction in cardiovascular mortality and a 24% decrease in coronary mortality for 10-year statin use compared with 5-year use for people given placebo in the original trial who later used statins. There was a suggestion that 10-year statin use was associated with a decreased incidence of cancer, although the 12% reduction for long-term statin users was not statistically significant.

Dr Strandberg comments: “The main finding of this 10-year follow-up study of the participants of 4S was that the survival benefit of patients allocated simvastatin compared with those allocated placebo that accrued during the double-blind trial period persisted during follow-up. The reduction in the relative risk between the two original treatment groups was not unexpected, because open-label treatment with lipid-lowering drugs (mostly statins) was given to most patients when the trial ended. After 3 years, more than 80% of patients in both groups were using these drugs. Nevertheless, the absolute differences in allcause, cardiovascular, and coronary mortality achieved during the double-blind trial changed little during the 5-year extension of the follow-up”.