Effect of high-dose atorvastatin on renal function in subjects with stroke or transient ischemic attack in the SPARCL trial

Pierre Amarenco; Alfred Callahan 3rd; Vito M Campese; Larry B Goldstein; Michael G Hennerici; Michael Messig; Henrik Sillesen; K Michael A Welch; Daniel J Wilson; Justin A Zivin

doi:10.1161/STROKEAHA.114.005832

Effect of high-dose atorvastatin on renal function in subjects with stroke or transient ischemic attack in the SPARCL trial

Stroke. 2014 Oct;45(10):2974-82. doi: 10.1161/STROKEAHA.114.005832. Epub 2014 Aug 21.

Affiliations

¹ Department of Neurology and Stroke Center, Paris-Diderot Sorbonne University, Paris, France (P.A.); Department of Neurology, Vanderbilt University, Nashville, TN (A.C.); Division of Nephrology and Hypertension Center, USC/Keck School of Medicine, Los Angeles, CA (V.M.C.); Department of Neurology, Duke University Medical Center, Durham, NC (L.B.G.); Department of Neurology, Universitat Heidelberg, Mannheim, Germany (M.G.H.); Pfizer Inc, New York, NY (M.M., D.J.W.); Department of Vascular Surgery, University of Copenhagen, Copenhagen, Denmark (H.S.); Office of the President, Rosalind Franklin University, Chicago, IL (K.M.A.W.); and Department of Neurology, University of California, San Diego (J.A.Z.). pierre.amarenco@bch.aphp.fr.
² Department of Neurology and Stroke Center, Paris-Diderot Sorbonne University, Paris, France (P.A.); Department of Neurology, Vanderbilt University, Nashville, TN (A.C.); Division of Nephrology and Hypertension Center, USC/Keck School of Medicine, Los Angeles, CA (V.M.C.); Department of Neurology, Duke University Medical Center, Durham, NC (L.B.G.); Department of Neurology, Universitat Heidelberg, Mannheim, Germany (M.G.H.); Pfizer Inc, New York, NY (M.M., D.J.W.); Department of Vascular Surgery, University of Copenhagen, Copenhagen, Denmark (H.S.); Office of the President, Rosalind Franklin University, Chicago, IL (K.M.A.W.); and Department of Neurology, University of California, San Diego (J.A.Z.).

PMID: 25147328
DOI: 10.1161/STROKEAHA.114.005832

Abstract

Background and purpose: Higher low-density lipoprotein cholesterol is associated with more rapid chronic kidney disease progression; reduction in cholesterol with statins, in conjunction with statins' pleiotropic effects, such as decreasing inflammation, may be renoprotective. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial assessed the effect of statin treatment on the risk of nonfatal and fatal stroke in subjects with a noncardioembolic stroke or transient ischemic attack, no known coronary heart disease, and low-density lipoprotein cholesterol between 2.6 and 4.9 mmol/L (100-190 mg/dL).

Methods: We explored the effect of randomization to atorvastatin 80 mg/d or placebo on the change in estimated glomerular filtration rate (eGFR; using the 4-component Modification of Diet in Renal Disease Study equation) in SPARCL subjects (n=4731) with (eGFR, <60 mL/min per 1.73 m2; n=3119) and without (eGFR, ≥60 mL/min per 1.73 m2; n=1600) chronic kidney disease overall and by glycemic status at baseline.

Results: Mean baseline eGFR was similar between treatment groups (65.5±0.26 versus 65.6±0.26 mL/min per 1.73 m2 atorvastatin versus placebo; 33% versus 34% had chronic kidney disease, respectively; P=0.55). After 60 months, eGFR increased 3.46±0.33 mL/min per 1.73 m2 in those randomized to atorvastatin versus 1.42±0.34 mL/min per 1.73 m2 in those randomized to placebo (P<0.001) independent of baseline renal function. In the subgroup with diabetes mellitus at randomization, eGFR increased 1.12±0.92 mL/min per 1.73 m2 in the atorvastatin group and decreased 1.69±0.92 mL/min per 1.73 m2 in placebo group during a period of 60 months (P=0.016).

Conclusions: This post hoc analysis suggests that atorvastatin treatment may improve renal function in patients with prior stroke or transient ischemic attack with and without chronic kidney disease, and that atorvastatin treatment may prevent eGFR decline in patients with stroke and diabetes mellitus.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00147602.

Keywords: atorvastatin; glomerular filtration rate; ischemic attack, transient; kidney diseases; renal insufficiency, chronic; stroke.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Atorvastatin
Double-Blind Method
Female
Glomerular Filtration Rate / drug effects*
Heptanoic Acids / therapeutic use*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Ischemic Attack, Transient / drug therapy*
Kidney / drug effects
Male
Middle Aged
Pyrroles / therapeutic use*
Stroke / drug therapy*

Substances

Heptanoic Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pyrroles
Atorvastatin

Associated data

ClinicalTrials.gov/NCT00147602