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Am J Kidney Dis. 2009 Nov;54(5):810-9. doi: 10.1053/j.ajkd.2009.03.022. Epub 2009 Jun 21.

Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS).

Collaborators (162)

Broom J, Tang K, Butt S, Lennox B, Collier A, Hampton J, Harris TJ, Tilley PJ, Reckless J, Widdowson EJ, Orpen LM, Fetherstone M, Hayes JR, McCance R, Allin DM, Dodson P, Martin U, Salman M, Dean J, Garrod GD, Jarvis C, Kerr D, Nelemans I, Heffer JS, Parfitt VJ, Brown MJ, Godfrey C, Newcombe GL, Barron J, Blagden M, Gaunt RM, Cowie A, Hillhouse E, Cooper AL, Jackson NW, Donnelly R, Kemp T, Rajeswaren C, Nolan J, Lawrence JR, McKenna MJ, Kilgallon B, Morris AD, Leese GP, Cohen HN, Benbow SJ, Walker JD, McKnight JA, Ambepitiya GB, Speirs C, Seaman A, Middleton A, Cahill TE, Weaver J, Razvi SS, Syed A, Scobie I, Small M, Paterson KR, Gallacher SJ, Fraser L, Kesson CM, Hammond P, MacLeod J, Thompson RW, Jowett N, Wheatley T, Johnston C, Baldasera M, Goozee P, MacRury S, Doig MF, McKeith DD, Gregory R, Burden AC, Meakin LC, Robinson J, Vora JP, Gray RS, Seed M, Leroux C, Dornhorst A, Tindall H, Press M, Symons RC, Young R, Wiles P, Parry HS, Dev D, Stephens WP, Lennon CH, Marshall S, Fisken R, Mansell PI, Patel V, Oelbaum RS, Horsley J, Bhatnagar D, Matthews D, Hinnie J, Ryan JF, Ellery A, Hall T, Gillespie K, Fletcher CP, White C, Howell J, Page MD, Shaw KM, Thomson M, Horne M, Shaw H, Gray NI, O'Hare JP, Hughes EJ, Cecil JR, O'Connell N, Cook RC, Beer S, King B, Hardy P, Patel NH, MacLeod A, Gunawardena KA, MacMahon M, Palmer P, Tayler TM, Leatherdale B, Sills D, Borthwick LJ, Kelly CJ, Reith SB, Ulliott E, Smith P, Lloyd-Mostyn R, Sands K, Davies PJ, Cummings P, Edwards PA, Ferry M, Jones AH, Evans PW, Rowlands SC, Duckworth MJ, Fleming S, Charlwood GJ, Nagi D, Bullen KR, Clements M, Robertson DA, Edwards R, Dayan C, Winocour P, Fraser J, O'Brien IA, Singh BM, Fulton JA, Millar L, Warner S, Harvey JN, Jennings P, Thow J.

Author information

1
Biomedical Research Institute, University of Dundee, Dundee, Scotland, UK. h.colhoun@cpse.dundee.ac.uk

Abstract

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 m(2). Atorvastatin treatment was associated with a modest improvement in annual change in eGFR (net, 0.18 mL/min/1.73 m(2)/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 m(2)/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 m(2), 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00327418.

PMID:
19540640
DOI:
10.1053/j.ajkd.2009.03.022
[Indexed for MEDLINE]
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