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. J.; Durrington, Paul N.; Hitman, G. A.; Neil, H. A. W.; Livingstone, Shona; Charlton-Menys, Valentine; DeMicco, David A.; Fuller, John

doi:10.1053/j.ajkd.2009.03.022

Cited by 229 publications

(147 citation statements)

References 23 publications

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“…17 Although a causal link remains to be established, recent findings in statin trials have demonstrated clear improvements in pre-ESRD mortality rates as well as the incidence of ESRD. 18,19 In this cohort, it is clear that statins have been underutilized and cholesterol lowering presents a potential means to prevent pre-ESRD death as well as ESRD itself.…”

Section: Clinical Epidemiology Wwwjasnorgmentioning

confidence: 97%

Competing-Risk Analysis of ESRD and Death among Patients with Type 1 Diabetes and Macroalbuminuria

Forsblom

Harjutsalo

Thorn

et al. 2011

Journal of the American Society of Nephrology

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Patients with both type 1 diabetes and CKD have an increased risk of adverse outcomes. The competing risks of death and ESRD may confound the estimates of risk for each outcome. Here, we sought to determine the major predictors of the cumulative incidence of ESRD and pre-ESRD mortality in patients with type 1 diabetes and macroalbuminuria while incorporating the competing risk for the alternate outcome into a Fine-Gray competing-risks analysis. We followed 592 patients with macroalbuminuria for a median of 9.9 years. During this time, 56 (9.5%) patients died and 210 (35.5%) patients developed ESRD. Predictors of incident ESRD, taking baseline renal function and the competing risk for death into account, included an elevated HbA 1c , elevated LDL cholesterol, male sex, weight-adjusted insulin dose, and a shorter duration of diabetes. By contrast, predictors of pre-ESRD death, taking baseline renal function and the competing risk for ESRD into account, included only age, the presence of established macrovascular disease, and elevated cholesterol levels. This competing-risks approach has potential to highlight the appropriate targets and strategies for preventing premature mortality in patients with type 1 diabetes. 22: 537-544, 201122: 537-544, . doi: 10.1681 The presence of overt nephropathy in patients with type 1 diabetes from Finland is associated with an increased risk of premature mortality that is over nine times that observed in the age-gender matched general population. 1 A number of different factors potentially contribute to this risk, including poor glycemic control and dyslipidemia. Epidemiologic understanding of the role different factors may play in these adverse outcomes has potentially been limited by cause-specific analyses that fail to take into account competing risks. 2 In particular, in individuals with macroalbuminuria, the outcomes of death and ESRD have important competing effects. For example, analysis of the predictors of ESRD needs to take into account the risk of dying before ESRD. Equally, the consequence of analyzing the predictors of death while taking into account the (proximal) risk of ESRD effectively limits exposure time to the pre-ESRD milieu and "hastens" exposure to the different risks associated with renal replacement therapy. This kind of analysis may be best performed within the paradigm of a formal competing-risks (Fine-Gray) proportional-hazards regression model, which estimates the cumulative incidence of an outcome while accounting for the competing risks of an J Am Soc Nephrol

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Section: Clinical Epidemiology Wwwjasnorgmentioning

confidence: 97%

Competing-Risk Analysis of ESRD and Death among Patients with Type 1 Diabetes and Macroalbuminuria

Forsblom

Harjutsalo

Thorn

et al. 2011

Journal of the American Society of Nephrology

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“…The effect of statins on diabetic nephropathy was examined in the Collaborative Atorvastatin Diabetes Study (CARDS) [32]. Treatment with atorvastatin was compared with a placebo in this study, and was associated with an improvement in annual changes in eGFR (0.18 mL/min/ 1.73 m 2 /year).…”

Section: Treatment Of Dyslipidemia and Diabetic Nephropathymentioning

confidence: 99%

Treatment and impact of dyslipidemia in diabetic nephropathy

et al. 2013

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Recent epidemiological research revealed that dyslipidemia is a risk factor for development and progression of diabetic nephropathy. Results from interventional studies revealed the possibility that antihyperlipidemic agents have a better effect on diabetic nephropathy through improvement of albuminuria and loss of renal function. In addition, dyslipidemia may be a consequence of albuminuria and renal dysfunction, thereby perpetuating kidney damage. Today, the proportion of diabetic patients receiving statins is increasing due to their beneficial effect on cardiovascular mortality. However, treatment for patients should be determined based on consideration of the risk and benefit of the treatment. More insight into the pathogenesis of diabetic nephropathy and the effects of life-style changes is required.

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“…The relative risk reductions in CKD patients were much better than in total subjects. A recent subanalysis of CARDS 70) , atrovastatin reduced the risk for MACE by 42% including a 61% reduction in stroke in type 2 diabetic patients with CKD stage 3. Although CKD was not the primary target population in the above studies, these post-hoc analyses strongly suggest that CKD is a subpopulation that may have for death from all causes, respectively.…”

Section: Lipid-lowering Treatment and Risk For Cvd In Ckd Stage 5dmentioning

confidence: 99%

“…Statin treatment is associated with increased eGFR or CCr as compared with a placebo in pot-hoc analyses of primary 69,70) and secondary prevention trials with statin 80,81) . Studies performed in Japan also provided similar results.…”

Section: Possible Reno-protective Effects Of Lipid-lowering Treatmentmentioning

confidence: 99%

Chronic Kidney Disease, Dyslipidemia, and Atherosclerosis

Shoji

Abe

Matsuo³

et al. 2012

JAT

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Patients with chronic kidney disease (CKD) are at an increased risk not only for end-stage kidney disease (ESKD) but also for cardiovascular disease (CVD). In this review article, we summarize the current evidence of CKD as a high-risk condition for CVD based on reports from Japan and other countries to draw attention to the close clinical association between CKD and CVD. Several epidemiologic studies have shown that the presence of CKD and reduced renal function are independent predictors of CVD also in Japan. According to a post-hoc analysis of CASE-J, the power of CKD as a predictor of CVD is as strong as diabetes mellitus and a previous history of ischemic heart disease. CKD worsens classical risk factors including hypertension and dyslipidemia, and dyslipidemia is associated with increased thickness and stiffness of large arteries independent of major confounders. A post-hoc analysis of MEGA indicates that lipid-lowering therapy with statins reduces the risk of CVD, and that it appears to be more efficacious in patients with than without CKD. These reports from Japan and other countries suggest that CKD should be regarded as a high-risk condition comparable to diabetes mellitus, and that strict control of dyslipidemia would be beneficial in preventing CVD, at least early stages of CKD.

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

Cited by 229 publications

References 23 publications

Competing-Risk Analysis of ESRD and Death among Patients with Type 1 Diabetes and Macroalbuminuria

Competing-Risk Analysis of ESRD and Death among Patients with Type 1 Diabetes and Macroalbuminuria

Treatment and impact of dyslipidemia in diabetic nephropathy

Chronic Kidney Disease, Dyslipidemia, and Atherosclerosis

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