Study of Heart and Renal Protection (SHARP): Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease

SHARP Collaborative Group

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Abstract

Background: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Methods: Patients with advanced CKD (blood creatinine ≥1.7 mg/dL [≥ 150 μmol/L] in men or ≥1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. Results A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. Conclusions SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.

Original languageEnglish (US)
Pages (from-to)785-794
Number of pages10
JournalAmerican Heart Journal
Volume160
Issue number5
DOIs
StatePublished - Nov 1 2010

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Simvastatin
Chronic Renal Insufficiency
LDL Cholesterol
Kidney
Placebos
Myocardial Infarction
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Muscular Diseases
Vascular Diseases
Dialysis
Creatinine
Diabetes Mellitus
Stroke
Safety
Ezetimibe
Liver
Incidence

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{9f747481dbaa4dbf97412a1cf0a3284b,
title = "Study of Heart and Renal Protection (SHARP): Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease",
abstract = "Background: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Methods: Patients with advanced CKD (blood creatinine ≥1.7 mg/dL [≥ 150 μmol/L] in men or ≥1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. Results A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. Conclusions SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.",
author = "{SHARP Collaborative Group} and C. Baigent and M. Landray and C. Reith and T. Dasgupta and J. Emberson and W. Herrington and D. Lewis and M. Mafham and R. Collins and C. Bray and Y. Chen and A. Baxter and A. Young and M. Hill and C. Knott and A. Cass and B. Feldt-Rasmussen and B. Fellstr{\"o}m and R. Grobbee and C. Gr{\"o}nhagen-Riska and M. Haas and H. Holdaas and Hooi, {L. S.} and L. Jiang and B. Kasiske and U. Krairittichai and A. Levin and Z. Massy and V. Tesar and R. Walker and C. Wanner and D. Wheeler and A. Wiecek and W. Majoni and D. Simpson and J. Strony and T. Musliner and L. Agodoa and J. Armitage and Z. Chen and J. Craig and {De Zeeuw}, D. and M. Gaziano and R. Grimm and V. Krane and B. Neal and V. Ophascharoensuk and T. Pedersen and P. Sleight and Csaba Kovesdy",
year = "2010",
month = "11",
day = "1",
doi = "10.1016/j.ahj.2010.08.012",
language = "English (US)",
volume = "160",
pages = "785--794",
journal = "American Heart Journal",
issn = "0002-8703",
publisher = "Mosby Inc.",
number = "5",

}

TY - JOUR

T1 - Study of Heart and Renal Protection (SHARP)

T2 - Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease

AU - SHARP Collaborative Group

AU - Baigent, C.

AU - Landray, M.

AU - Reith, C.

AU - Dasgupta, T.

AU - Emberson, J.

AU - Herrington, W.

AU - Lewis, D.

AU - Mafham, M.

AU - Collins, R.

AU - Bray, C.

AU - Chen, Y.

AU - Baxter, A.

AU - Young, A.

AU - Hill, M.

AU - Knott, C.

AU - Cass, A.

AU - Feldt-Rasmussen, B.

AU - Fellström, B.

AU - Grobbee, R.

AU - Grönhagen-Riska, C.

AU - Haas, M.

AU - Holdaas, H.

AU - Hooi, L. S.

AU - Jiang, L.

AU - Kasiske, B.

AU - Krairittichai, U.

AU - Levin, A.

AU - Massy, Z.

AU - Tesar, V.

AU - Walker, R.

AU - Wanner, C.

AU - Wheeler, D.

AU - Wiecek, A.

AU - Majoni, W.

AU - Simpson, D.

AU - Strony, J.

AU - Musliner, T.

AU - Agodoa, L.

AU - Armitage, J.

AU - Chen, Z.

AU - Craig, J.

AU - De Zeeuw, D.

AU - Gaziano, M.

AU - Grimm, R.

AU - Krane, V.

AU - Neal, B.

AU - Ophascharoensuk, V.

AU - Pedersen, T.

AU - Sleight, P.

AU - Kovesdy, Csaba

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Methods: Patients with advanced CKD (blood creatinine ≥1.7 mg/dL [≥ 150 μmol/L] in men or ≥1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. Results A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. Conclusions SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.

AB - Background: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Methods: Patients with advanced CKD (blood creatinine ≥1.7 mg/dL [≥ 150 μmol/L] in men or ≥1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. Results A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. Conclusions SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.

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U2 - 10.1016/j.ahj.2010.08.012

DO - 10.1016/j.ahj.2010.08.012

M3 - Article

C2 - 21095263

AN - SCOPUS:78650184434

VL - 160

SP - 785

EP - 794

JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

IS - 5

ER -