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Effect of high-dose atorvastatin on renal function in subjects with stroke or transient ischemic attack in the SPARCL
Pierre Amarenco1, Alfred Callahan2, Vito M Campese2
1Department 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.
Insights
Atorvastatin may improve kidney function in patients with a history of stroke or TIA, regardless of chronic kidney disease status. This statin treatment also appears to prevent estimated glomerular filtration rate decline in stroke patients with diabetes.
Area of Science:
- Nephrology
- Cardiology
- Neurology
Background:
- Elevated low-density lipoprotein cholesterol (LDL-C) is linked to faster chronic kidney disease (CKD) progression.
- Statins, through cholesterol reduction and pleiotropic effects like anti-inflammation, may offer renoprotection.
- The SPARCL trial investigated atorvastatin's effect on stroke risk in patients with specific risk factors.
Purpose of the Study:
- To evaluate the impact of atorvastatin on estimated glomerular filtration rate (eGFR) changes in SPARCL participants.
- To analyze these effects in patients with and without pre-existing chronic kidney disease.
- To assess the influence of glycemic status on atorvastatin's renal effects.
Main Methods:
- A post hoc analysis of the SPARCL trial (n=4731) was conducted.
- Participants were randomized to atorvastatin 80 mg/day or placebo.
- Changes in eGFR, calculated using the MDRD equation, were analyzed over 60 months, stratified by baseline renal function and diabetes status.
Main Results:
- Atorvastatin treatment led to a significant increase in eGFR over 60 months compared to placebo (3.46 vs 1.42 mL/min per 1.73 m2, P<0.001), irrespective of baseline renal function.
- In patients with diabetes, atorvastatin increased eGFR (1.12 mL/min per 1.73 m2), while placebo showed a decrease (-1.69 mL/min per 1.73 m2) over 60 months (P=0.016).
- Baseline eGFR and prevalence of CKD were similar between atorvastatin and placebo groups.
Conclusions:
- Atorvastatin treatment may enhance renal function in patients with prior stroke or TIA, with or without CKD.
- Atorvastatin demonstrated a potential to prevent eGFR decline in stroke patients who also have diabetes mellitus.
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.
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