Effects of Atorvastatin on Kidney Outcomes and Cardiovascular Disease in Patients With Diabetes: An Analysis From the Collaborative Atorvastatin Diabetes Study (CARDS)

Colhoun, Helen M.; Betteridge, D. John; Durrington, Paul N.; Hitman, Graham A.; Neil, H. Andrew W.; Livingstone, Shona J.; Charlton-Menys, Valentine; DeMicco, David A.; Fuller, John H.; CARDS Investigators,

doi:10.1053/j.ajkd.2009.03.022

« Previous Next »American Journal of Kidney Diseases
Volume 54, Issue 5 , Pages 810-819, November 2009

Effects of Atorvastatin on Kidney Outcomes and Cardiovascular Disease in Patients With Diabetes: An Analysis From the Collaborative Atorvastatin Diabetes Study (CARDS)

Helen M. Colhoun, MD
- University of Dundee, Dundee, Scotland, UK
- Address correspondence to Helen M. Colhoun, MD, Biomedical Research Institute, University of Dundee, Mackenzie Bldg, Kirsty Semple Way, Dundee, DD2 4BF Scotland, UK
D. John Betteridge, PhD
- University College London Hospital, London, UK
Paul N. Durrington, MD
- Cardiovascular Research Group, School of Clinical and Laboratory Sciences, Core Technology Facility, University of Manchester, UK
Graham A. Hitman, MD
- Centre for Diabetes and Metabolic Medicine, Barts and the London School of Medicine and Dentistry, London, UK
H. Andrew W. Neil, DSc
- University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK
Shona J. Livingstone, MSc
- University of Dundee, Dundee, Scotland, UK
Valentine Charlton-Menys, PhD
- Cardiovascular Research Group, School of Clinical and Laboratory Sciences, Core Technology Facility, University of Manchester, UK
David A. DeMicco, PharmD
- Pfizer, New York, NY
John H. Fuller, FRCP
- EURODIAB, Department of Epidemiology and Public Health, Royal Free and University of London Medical School, London, UK
CARDS Investigators

Received 5 December 2008; accepted 27 March 2009. published online 22 June 2009.

Background

We examined whether atorvastatin affects diabetic kidney disease and whether the effect of atorvastatin on cardiovascular disease (CVD) varies by kidney status in patients with diabetes.

Study Design

The Collaborative Atorvastatin Diabetes Study (CARDS) randomized placebo-controlled trial.

Setting & Participants

Patients with type 2 diabetes and no prior CVD (n = 2,838).

Intervention

Random allocation to atorvastatin, 10 mg/d, or placebo, with a median follow-up of 3.9 years.

Outcomes

Estimated glomerular filtration rate (eGFR), albuminuria, CVD.

Measurements

Baseline and follow-up GFRs were estimated by using the Modification of Diet in Renal Disease Study equation. Urinary albumin-creatinine ratio was measured on spot urine samples.

Results

At baseline, 34% of patients had an eGFR of 30 to 60 mL/min/1.73 m². Atorvastatin treatment was associated with a modest improvement in annual change in eGFR (net, 0.18 mL/min/1.73 m²/y; 95% confidence interval [CI], 0.04 to 0.32; P = 0.01) that was most apparent in those with albuminuria (net improvement, 0.38 mL/min/1.73 m²/y; P = 0.03). At baseline, 21.5% of patients had albuminuria and an additional 6.8% developed albuminuria during follow-up. Atorvastatin did not influence the incidence of albuminuria (hazard ratio, 1.49; 95% CI, 0.73 to 3.04; P = 0.3) or regression to normoalbuminuria (hazard ratio, 1.19; 95% CI, 0.57 to 2.49; P = 0.6). In 970 patients with a moderately decreased eGFR of 30 to 60 mL/min/1.73 m², there was a 42% reduction in major CVD events with treatment, including a 61% reduction in stroke. This treatment effect was similar to the 37% (95% CI, 17 to 52; P < 0.001) reduction in CVD observed in the study overall (P = 0.4 for the eGFR-treatment interaction).

Limitations

Low incidence rates of albuminuria and transition to more severe kidney status limit power to detect treatment effects.

Conclusions

A modest beneficial effect of atorvastatin on eGFR, particularly in those with albuminuria, was observed. Atorvastatin did not influence albuminuria incidence. Atorvastatin was effective at decreasing CVD in those with and without a moderately decreased eGFR and achieved a high absolute benefit.

Index Words: Statin, diabetes, cardiovascular, eGFR, albuminuria