Renal safety of intensive cholesterol-lowering treatment with rosuvastatin: a retrospective analysis of renal adverse events among 40,600 participants in the rosuvastatin clinical development program

Atherosclerosis. 2012 Apr;221(2):471-7. doi: 10.1016/j.atherosclerosis.2011.12.011. Epub 2012 Jan 3.

Abstract

Objective: Intensive lowering of low-density lipoprotein cholesterol (LDL-C) with statins reduces cardiovascular risk but can cause liver-, muscle-, and possibly renal-related adverse events (AEs). We assessed the effects of rosuvastatin on the risk of developing renal impairment or renal failure among participants in the rosuvastatin clinical development program.

Methods: The analysis was based on AE data reported by investigators from 36 studies that included 40,600 participants who did not have advanced, pre-existing renal disease. Rates of renal AEs were determined based on time to first occurrence of renal impairment or renal failure.

Results: Renal impairment or renal failure was reported in 536 study participants during 72,488 patient-years of follow-up. Renal event rates were higher in patients with history of heart failure (n = 5011), hypertension (n = 21,864), diabetes (n = 5165), or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) (n = 9507) at baseline but did not differ with rosuvastatin compared with placebo or with rosuvastatin 40 mg compared with rosuvastatin 10mg. Relative risk (RR) estimates obtained from pooled analysis of placebo-controlled trials were RR: 1.03 (95% CI: 0.86-1.23, p = 0.777) for any reported renal impairment or renal failure event, RR: 1.02 (95% CI: 0.76-1.37, p = 0.894) for serious renal AEs, and RR: 0.70 (95% CI: 0.36-1.35, p = 0.282) for renal AEs leading to death.

Conclusion: These findings suggest that intensive LDL-C-lowering treatment with rosuvastatin does not affect the risk of developing renal insufficiency or renal failure in patients who do not have advanced, pre-existing renal disease.

Trial registration: ClinicalTrials.gov NCT00206310 NCT00225589 NCT00239681.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cholesterol, LDL / blood
  • Clinical Trials as Topic
  • Evidence-Based Medicine
  • Female
  • Fluorobenzenes / adverse effects*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Pyrimidines / adverse effects*
  • Renal Insufficiency / chemically induced*
  • Renal Insufficiency / physiopathology
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Rosuvastatin Calcium
  • Sulfonamides / adverse effects*
  • Time Factors

Substances

  • Biomarkers
  • Cholesterol, LDL
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium

Associated data

  • ClinicalTrials.gov/NCT00206310
  • ClinicalTrials.gov/NCT00225589
  • ClinicalTrials.gov/NCT00239681