Effect of High-Dose Atorvastatin on Renal Function in Subjects With Stroke or Transient Ischemic Attack in the SPARCL Trial

AmarencoP, Callahan A, Campese VM 3rd, et al.
Stroke. 2014 Aug 21. pii: STROKEAHA.114.005832. [Epub ahead of print]

Background

To reduce the cardiovascular disease (CVD) risk associated with chronic kidney disease (CKD) and to prevent progressive impairment of renal function, aggressive treatment of comorbid conditions is recommended [1-3]. It has been shown that higher LDL-c levels are associated with a more rapid decrease in estimated glomerular filtration rate (eGFR) [4,5] and lowering LDL-c with statins may be renoprotective in subjects with CVD [6,7]. Several trials have shown improvements in eGFR with statin treatment, both in subjects with or without CKD [8-12].
In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, patients with recent noncardioembolic stroke or transient ischaemic attack (TIA) without known coronary heart disease (CHD) were randomised to atorvastatin 80 mg/d or placebo. Treatment was associated with lower stroke risk and major coronary events [13]. This paper describes a post hoc analysis of SPARCL data that explored the effect of atorvastatin 80 mg/d vs. placebo on changes in renal function from baseline (eGFR) in those with (n=1600) and without (eGFR >60 mL/min per 1.73m², n=3119) CKD at baseline. Subjects with CKD had a baseline eGFR of 52.3±7.0 mL/min per 1.73 m² compared with an eGFR of 72.3±8.9 mL/min per 1.73 m² in those without CKD (P<0.001).

Main results

• After 60 months of treatment with atorvastatin, eGFR increased with 3.46+0.33 as compared with 1.42+0.34 mL/min per 1.73m² in the placebo group. Improvements with atorvastatin vs. placebo were seen after 12, 24, 36, 48 and 60 months of therapy. No significant treatment by time interaction was seen.
• The improvement of eGFR with statin treatment did not depend on baseline renal function: at 60 months, atorvastatin-treated subjects with CKD showed a least squares mean rise in eGFR of 4.24+0.60 mL/min per 1.73m², whereas those without CKD had a 3.27+0.40 mL/min per 1.73m² increase. An improvement of eGFR was also seen in patients with placebo, but the rise was significantly larger in patients on atorvastatin.
• In subjects without CKD at baseline, fewer individuals on atorvastatin had a decline in kidney function to eGFR<60 mL/min during the trial than those assigned to placebo (10.6% vs. 14.1%, P=0.005). A greater proportion of atorvastatin-treated individuals had better kidney function at the end of the study as compared with placebo (34.1% vs. 29.3%, P=0.050).
• In patients with diabetes mellitus at randomisation, patients on placebo showed a decline in eGFR during the study (-1.69+0.92 mL/min per 1.73m²), while patients on atorvastatin showed a 1.12+0.92 mL/min per 1.73 m² increase (P=0.016).
• Persistent elevations in hepatic transaminase levels occurred more often in atorvastatin-treated subjects than in placebo, but overall rates were low, and similar between those with (2.4%) and without (2.0%) CKD. Persistent elevations in creatine phosphokinase levels were also similar between subjects with and without CKD.

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Conclusion

This posthoc analysis suggests that treatment with atorvastatin 80 mg/d improves eGFR as compared with placebo, in a population of subjects with prior stroke or TIA. The decline in renal function seen in subjects who had diabetes at baseline, was largely halted in subjects randomised to atorvastatin. The renoprotective effects of atorvastatin 80 mg/d were seen within 1 year, and maintained for 60 months, and were seen in patient with and without CKD at baseline.

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