EFFECTS OF ATORVASTATIN AND ROSUVASTATIN ON RENAL FUNCTION IN PATIENTS AT HIGH CARDIOVASCULAR RISK: A META-ANALYSIS OF 23 RANDOMIZED TRIALS

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1 EFFECTS OF ATORVASTATIN AND ROSUVASTATIN ON RENAL FUNCTION IN PATIENTS AT HIGH CARDIOVASCULAR RISK: A META-ANALYSIS OF 23 RANDOMIZED TRIALS Gianluigi Savarese, MD 1, Massimo Volpe, MD, PhD 2, Francesca Musella, MD 1, Laura Casaretti, MD 1, Pasquale Perrone Filardi, MD, PhD 1 1 Department of Internal Medicine, Cardiovascular and Immunological Sciences, Federico II University, Naples, Italy 2 Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy Declaration of conflict of interest: none to declare

2 Background and Purpose Atorvastatin and Rosuvastatin are highly effective and widely used statins. Conflicting results have been reported regarding their renal effects. Purpose of the study was to evaluate the effects of atorvastatin and rosuvastatin on glomerular filtration rate (GFR) and new proteinuria onset in patients at high cardiovascular risk.

3 Methods

4 Methods Inclusion Criteria: report of GFR at baseline and at end of follow-up or report of change of GFR from baseline to end of follow-up; report of new proteinuria onset (defined as dipstick >++); randomized protocol design; comparison of atorvastatin or rosuvastatin versus placebo for GFR evaluation; comparison of atorvastatin versus rosuvastatin for GFR and new proteinuria onset evaluation.

5 Methods Statistical Analysis: Meta-analysis was performed to assess the influence of treatments on GFR and new proteinuria onset. Statistical homogeneity was assessed using Q statistic and further quantified with the I2 statistic. Meta-regression was performed to test the influence of potential effect modifiers on results. Publication bias was assessed using linear regression test by Egger and Macaskill s modified test.

6 GFR changes from baseline to end of follow-up evaluation in statin versus placebo study groups. p<0.001

7 SMD estimate of GFR changes from baseline to end of follow-up evaluation in atorvastatin versus placebo study groups. P=0.031

8 SMD estimate of GFR changes from baseline to end of follow-up evaluation in rosuvastatin versus placebo study groups. P=0.001

9 SMD estimate of GFR changes from baseline to end of followup evaluation in atorvastatin versus rosuvastatin study groups. P=0.319 SMD estimate of GFR changes from baseline to end of followup evaluation in atorvastatin 80 mg/daily versus rosuvastatin 40 mg/daily study groups. P=0.050

10 OR estimate of new proteinuria onset in atorvastatin versus rosuvastatin study groups. P=0.181 Favour Atorvastatin Favour Rosuvastatin

11 SMD estimate of GFR changes from baseline to end of follow-up evaluation in statins versus placebo groups in studies enrolling patients with chronic kidney disease P<0.01

12 SMD estimate of GFR changes from baseline to end of follow-up evaluation in atorvastatin versus placebo groups in studies enrolling patients with chronic kidney disease

13 SMD estimate of GFR changes from baseline to end of follow-up evaluation in rosuvastatin versus placebo groups in studies enrolling patients with chronic kidney disease

14 Statins improved GFR compared to placebo. Both atorvastatin and rosuvastatin improved GFR compared to placebo. In head-to-head studies comparing atorvastatin to rosuvastatin, no significant difference in GFR was detected. Rosuvastatin significantly increased the risk of proteinuria onset when compared to atorvastatin, but this effect was no longer significant when studies using rosuvastatin 40 mg/daily were excluded from analysis, abolishing significant heterogeneity. In trials enrolling only patients with chronic kidney disease, statins led to a significant improvement in GFR compared to placebo. However, GFR was improved by atorvastatin, but it was not significantly changed by rosuvastatin.

15 Conclusions Atorvastatin and rosuvastatin comparably reduce the decline of renal function in patients at high cardiovascular risk without chronic kidney disease Atorvastatin improves renal function in high-risk patients with chronic kidney disease. These favourable effects may contribute to the cardiovascular protection granted by these drugs in randomized clinical trials.