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Effect of pravastatin in people with diabetes and chronic kidney disease.
J Am Soc Nephrol. 2005 Dec; 16(12):3748-54.JA

Abstract

Although diabetes is a major cause of chronic kidney disease (CKD), limited data describe the cardiovascular benefit of hydroxymethyl glutaryl CoA reductase inhibitors (statins) in people with both of these conditions. This study sought to determine whether pravastatin reduced the incidence of first or recurrent cardiovascular events in people with non-dialysis-dependent CKD and concomitant diabetes, using data from three randomized trials of pravastatin 40 mg daily versus placebo. CKD was defined by estimated GFR <60 or 60 to 89.9 ml/min per 1.73 m2 with proteinuria. Of 19,737 patients, 4099 (20.8%) had CKD but not diabetes at baseline, 873 (4.4%) had diabetes but not CKD, and 571 (2.9%) had both conditions. The primary composite outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Median follow-up was 64 mo. After adjustment for trial and random treatment assignment, the incidence of the primary outcome was lowest in individuals with neither CKD nor diabetes (15.2%), intermediate in individuals with only CKD (18.6%) or only diabetes (21.3%), and highest in individuals with both characteristics (27.0%). Pravastatin reduced the relative likelihood of the primary outcome to a similar extent in subgroups defined by the presence or absence of CKD and diabetes. For example, pravastatin was associated with a significant reduction in the relative risk of the primary outcome by 25% in patients with CKD and concomitant diabetes and by 24% in individuals with neither characteristic. However, the absolute reduction in the risk of the primary outcome as a result of pravastatin use was highest in patients with both CKD and diabetes (6.4%) and lowest in individuals with neither characteristic (3.5%). In conclusion, stage 2 or early stage 3 CKD and diabetes both are associated with higher cardiovascular risk, and pravastatin reduces cardiovascular event rates in people with neither, one, or both characteristics. Given the high absolute benefit of pravastatin in patient with diabetes and stage 2 or early stage 3 CKD, this population in particular should be targeted for widespread use of statins. Additional studies are needed to determine whether these benefits apply to patients with more severe CKD, and recruitment to such studies should be given high priority.

Authors+Show Affiliations

Tonelli M
Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada. mtonelli@ualberta.ca
Keech A
No affiliation info available
Shepherd J
No affiliation info available
Sacks F
No affiliation info available
Tonkin A
No affiliation info available
Packard C
No affiliation info available
Pfeffer M
No affiliation info available
Simes J
No affiliation info available
Isles C
No affiliation info available
Furberg C
No affiliation info available
West M
No affiliation info available
Craven T
No affiliation info available
Curhan G
No affiliation info available

MeSH

AdultAge DistributionAgedCardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiddle AgedPravastatinPrevalenceProbabilityPrognosisRenal Insufficiency, ChronicRisk AssessmentSex DistributionTreatment Outcome

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16251235

Citation

Tonelli, Marcello, et al. "Effect of Pravastatin in People With Diabetes and Chronic Kidney Disease." Journal of the American Society of Nephrology : JASN, vol. 16, no. 12, 2005, pp. 3748-54.
Tonelli M, Keech A, Shepherd J, et al. Effect of pravastatin in people with diabetes and chronic kidney disease. J Am Soc Nephrol. 2005;16(12):3748-54.
Tonelli, M., Keech, A., Shepherd, J., Sacks, F., Tonkin, A., Packard, C., Pfeffer, M., Simes, J., Isles, C., Furberg, C., West, M., Craven, T., & Curhan, G. (2005). Effect of pravastatin in people with diabetes and chronic kidney disease. Journal of the American Society of Nephrology : JASN, 16(12), 3748-54.
Tonelli M, et al. Effect of Pravastatin in People With Diabetes and Chronic Kidney Disease. J Am Soc Nephrol. 2005;16(12):3748-54. PubMed PMID: 16251235.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of pravastatin in people with diabetes and chronic kidney disease. AU - Tonelli,Marcello, AU - Keech,Anthony, AU - Shepherd,Jim, AU - Sacks,Frank, AU - Tonkin,Andrew, AU - Packard,Chris, AU - Pfeffer,Marc, AU - Simes,John, AU - Isles,Chris, AU - Furberg,Curt, AU - West,Malcolm, AU - Craven,Tim, AU - Curhan,Gary, Y1 - 2005/10/26/ PY - 2005/10/28/pubmed PY - 2006/4/28/medline PY - 2005/10/28/entrez SP - 3748 EP - 54 JF - Journal of the American Society of Nephrology : JASN JO - J Am Soc Nephrol VL - 16 IS - 12 N2 - Although diabetes is a major cause of chronic kidney disease (CKD), limited data describe the cardiovascular benefit of hydroxymethyl glutaryl CoA reductase inhibitors (statins) in people with both of these conditions. This study sought to determine whether pravastatin reduced the incidence of first or recurrent cardiovascular events in people with non-dialysis-dependent CKD and concomitant diabetes, using data from three randomized trials of pravastatin 40 mg daily versus placebo. CKD was defined by estimated GFR <60 or 60 to 89.9 ml/min per 1.73 m2 with proteinuria. Of 19,737 patients, 4099 (20.8%) had CKD but not diabetes at baseline, 873 (4.4%) had diabetes but not CKD, and 571 (2.9%) had both conditions. The primary composite outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Median follow-up was 64 mo. After adjustment for trial and random treatment assignment, the incidence of the primary outcome was lowest in individuals with neither CKD nor diabetes (15.2%), intermediate in individuals with only CKD (18.6%) or only diabetes (21.3%), and highest in individuals with both characteristics (27.0%). Pravastatin reduced the relative likelihood of the primary outcome to a similar extent in subgroups defined by the presence or absence of CKD and diabetes. For example, pravastatin was associated with a significant reduction in the relative risk of the primary outcome by 25% in patients with CKD and concomitant diabetes and by 24% in individuals with neither characteristic. However, the absolute reduction in the risk of the primary outcome as a result of pravastatin use was highest in patients with both CKD and diabetes (6.4%) and lowest in individuals with neither characteristic (3.5%). In conclusion, stage 2 or early stage 3 CKD and diabetes both are associated with higher cardiovascular risk, and pravastatin reduces cardiovascular event rates in people with neither, one, or both characteristics. Given the high absolute benefit of pravastatin in patient with diabetes and stage 2 or early stage 3 CKD, this population in particular should be targeted for widespread use of statins. Additional studies are needed to determine whether these benefits apply to patients with more severe CKD, and recruitment to such studies should be given high priority. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/16251235/Effect_of_pravastatin_in_people_with_diabetes_and_chronic_kidney_disease_ DB - PRIME DP - Unbound Medicine ER -