Rizwan Kalani, MD

Amarenco P, Callahan A, Campese III VM, Goldstein LB, Hennerici MG, Messig M, et al. Effect of High-Dose Atorvastatin on Renal Function in Subjects With Stroke or Transient Ischemic Attack in the SPARCL Trial. Stroke. 2014

Chronic kidney disease (CKD) shares many risk factors with cerebrovascular disease – principally hypertension, diabetes, and dyslipidemia. Lowering low-density lipoprotein (LDL) cholesterol in patients with dyslipidemia and coronary artery disease or diabetes has been shown to be renoprotective in addition to reducing cardiovascular events. CKD has several implications for patients with cerebrovascular disease including conferring an increased risk for stroke and being an independent predictor of mortality and outcomes after stroke. Thus, CKD, which is also a global public health problem, should also be of interest to neurologists.

In this study, Amarenco et al conducted a post-hoc analysis of data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. The effect of atorvastatin 80mg per day (vs. placebo) on change in renal function, measured by estimated glomerular filtration rate (GFR), in patients with and without baseline CKD was assessed. Those with GFR<60 ml/min/1.73m2 were defined as having CKD. Secondary analysis by baseline glycemic/metabolic status (presence or absence of type 2 diabetes and metabolic syndrome) was also conducted given its effects on renal function.
Of the 4731 SPARCL patients, 4393 had available serial renal function data (66% had GFR>60 at baseline, and 34% had CKD – majority of which had stage 3 CKD [GFR of 30-59]). Baseline GFR was similar between the statin and placebo groups. There was significant improvement in GFR in the atorvastatin-treated group (vs placebo) after 1, 2, 3, 4, and 5 years of treatment. The GFR increase (from baseline) at 5 years in the statin group averaged 3.46 vs 1.42 in the placebo group (p<0.001). This improvement was independent of initial renal function – in those with CKD, the atorvastatin-treated patients had a mean 4.24 rise in GFR at 5 years whereas those without CKD had an average 3.27 increase. This was seen in the setting of a 40% reduction in LDL in patients with CKD and a 37% reduction in those without CKD. In those with a history of diabetes at baseline, an average GFR increase of 1.12 was seen in the statin group vs a decrease of 1.69 in the placebo group (at 5 years) (p=0.016).

This study is consistent with prior reports suggestive of the idea that statin treatment is nephroprotective in high-risk patients with vascular disease. In the SPARCL patient population, an effect was seen within a year and is maintained for the 5 years of follow-up. Its important to note that the study cohort also had adequate blood pressure control and appropriate management of other vascular risk factors. Also, a small number of patients in this study had stage 4 or 5 CKD, so it is difficult to assess if 80mg atorvastatin treatment could benefit those with more severe renal dysfunction. Though the degree of improvement in GFR may seem modest, this is just another reason to use high intensity statin (atorvastatin) after non-cardioembolic stroke/TIA.