Effect of simvastatin on kidney function loss in patients with coronary heart disease: findings from the Scandinavian Simvastatin Survival Study (4S)

Atherosclerosis. 2009 Jul;205(1):202-6. doi: 10.1016/j.atherosclerosis.2008.11.010. Epub 2008 Nov 18.


Objective: Statins have been hypothesized to slow loss of kidney function, however, data is conflicting. This study assessed whether simvastatin reduces rates of kidney function loss in participants with coronary heart disease (CHD).

Methods: We performed a post hoc analysis from the Scandinavian Simvastatin Survival Study, a randomized trial of simvastatin vs. placebo in 4444 men and women with CHD. Kidney disease progression defined as the occurrence of a >or=25% reduction in estimated glomerular filtration rate (GFR) from baseline or development of chronic kidney disease (CKD), defined as estimated GFR <60 mL/min/1.73 m(2). The annual rate of change in estimated GFR was also evaluated. Estimated GFR was determined by the Modified Diet and Renal Disease Study equation.

Results: Change in kidney function could be calculated in 3842 subjects, of whom 409 had CKD at baseline. In the whole population, simvastatin significantly reduced the frequency of a >or=25% decline in kidney function [adjusted odds ratio (OR) 0.68, 95% confidence interval (CI), 0.50-0.92; p=0.01] during 5.5 years of follow-up. The adjusted annualized least-square mean decline in estimated GFR in the simvastatin group was lower than that in the placebo group (0.34 mL/min/1.73 m(2)/year vs. 0.41 mL/min/1.73 m(2)/year, respectively; p=0.02). There was no significant effect of simvastatin on kidney function in the subgroup of participants (n=363), who developed incident CKD at the end of follow-up [adjusted OR: 0.89 (95% CI 0.70-1.14; p=0.36)].

Conclusion: Simvastatin was associated with a moderate protective effect on the rate of kidney function loss in participants with CHD.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Coronary Disease / drug therapy*
  • Diet
  • Disease Progression
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney / drug effects*
  • Male
  • Middle Aged
  • Placebos
  • Scandinavian and Nordic Countries
  • Simvastatin / pharmacology*
  • Treatment Outcome


  • Placebos
  • Simvastatin