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.
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.


CONCLUSIONS
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.
Medpace Reference Laboratories, Inc, 4620 Wesley Avenue, Cincinnati, OH 45212, USA. ESteinMRL@aol.com
Evan A
EA
Stein
Donald G
DG
Vidt
James
J
Shepherd
Valerie A
VA
Cain
Deborah
D
Anzalone
Michael D
MD
Cressman
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D019317:Evidence-Based Medicine; D005260:Female; D005464:Fluorobenzenes / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000009:adverse effects*; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000503:physiopathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000009:adverse effects*; D013997:Time Factors
D015415:Biomarkers; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium