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

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.

High-dose atorvastatin and risk of atrial fibrillation in patients with prior stroke or transient ischemic attack: analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

BACKGROUND: Observational analyses and short-term randomized trials have suggested that statins reduce occurrence or recurrence of atrial fibrillation (AF). We tested the hypothesis that long-term treatment with high-dose atorvastatin reduces occurrence of AF in patients with prior stroke or transient ischemic attack. METHODS: We examined development of new AF in the SPARCL trial that compared atorvastatin 80 mg daily with placebo in 4,731 patients with prior stroke or transient ischemic attack. Patients who had chronic or paroxysmal AF or were taking medications for treatment or prophylaxis of AF at the time of enrollment were excluded. Atrial fibrillation was identified from electrocardiograms submitted to a blinded central electrocardiographic laboratory and from investigators' adverse event reports. RESULTS: Patients were followed up for a median of 4.8 years, corresponding to >20,000 patient-years of observation with a median of 5 electrocardiograms per patient. The primary efficacy measure, the time from randomization to first occurrence of new AF, did not differ between treatment groups. By intention to treat, there were 139 cases of new AF in the atorvastatin group and 122 cases in the placebo group, corresponding to incidence rates of 1.32 and 1.14 cases per 100 patient-years observation (hazard ratio 1.15, 95% CI 0.90-1.46, P = .26). On-treatment analysis yielded similar findings, with incidence rates of 1.26 and 1.01 cases per 100 patient-years observation in the atorvastatin and placebo groups, respectively (hazard ratio 1.25, 95% CI 0.94-1.67, P = .12). CONCLUSION: High-dose atorvastatin does not prevent development of AF in patients with prior stroke or transient ischemic attack.