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The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial

Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial... Full description

Journal Title: Lancet 2011, Vol.377 (9784), p.2181-2192
Main Author: Baigent, Colin, Prof
Other Authors: Landray, Martin J, FRCP , Reith, Christina, MRCP , Emberson, Jonathan, PhD , Wheeler, David C, FRCP , Tomson, Charles, DM , Wanner, Christoph, Prof , Krane, Vera, MD , Cass, Alan, Prof , Craig, Jonathan, Prof , Neal, Bruce, Prof , Jiang, Lixin, MD , Hooi, Lai Seong, FRCP , Levin, Adeera, Prof , Agodoa, Lawrence, Prof , Gaziano, Mike, Prof , Kasiske, Bertram, Prof , Walker, Robert, Prof , Massy, Ziad A, Prof , Feldt-Rasmussen, Bo, Prof , Krairittichai, Udom, MD , Ophascharoensuk, Vuddidhej, MD , Fellström, Bengt, Prof , Holdaas, Hallvard, MD , Tesar, Vladimir, Prof , Wiecek, Andrzej, Prof , Grobbee, Diederick, Prof , de Zeeuw, Dick, Prof , Grönhagen-Riska, Carola, Prof , Dasgupta, Tanaji, MRCP , Lewis, David, MRCP , Herrington, William, MRCP , Mafham, Marion, MD , Majoni, William, FRACP , Wallendszus, Karl, MSc , Grimm, Richard, Prof , Pedersen, Terje, Prof , Tobert, Jonathan, PhD , Armitage, Jane, Prof , Baxter, Alex, BA , Bray, Christopher, PhD , Chen, Yiping, DPhil , Chen, Zhengming, Prof , Hill, Michael, DPhil , Knott, Carol, MSc , Parish, Sarah, DPhil , Simpson, David , Sleight, Peter, Prof , Young, Alan, DPhil , Collins, Rory, Prof
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Kidlington: Elsevier Ltd
ID: ISSN: 0140-6736
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title: The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
format: Article
creator:
  • Baigent, Colin, Prof
  • Landray, Martin J, FRCP
  • Reith, Christina, MRCP
  • Emberson, Jonathan, PhD
  • Wheeler, David C, FRCP
  • Tomson, Charles, DM
  • Wanner, Christoph, Prof
  • Krane, Vera, MD
  • Cass, Alan, Prof
  • Craig, Jonathan, Prof
  • Neal, Bruce, Prof
  • Jiang, Lixin, MD
  • Hooi, Lai Seong, FRCP
  • Levin, Adeera, Prof
  • Agodoa, Lawrence, Prof
  • Gaziano, Mike, Prof
  • Kasiske, Bertram, Prof
  • Walker, Robert, Prof
  • Massy, Ziad A, Prof
  • Feldt-Rasmussen, Bo, Prof
  • Krairittichai, Udom, MD
  • Ophascharoensuk, Vuddidhej, MD
  • Fellström, Bengt, Prof
  • Holdaas, Hallvard, MD
  • Tesar, Vladimir, Prof
  • Wiecek, Andrzej, Prof
  • Grobbee, Diederick, Prof
  • de Zeeuw, Dick, Prof
  • Grönhagen-Riska, Carola, Prof
  • Dasgupta, Tanaji, MRCP
  • Lewis, David, MRCP
  • Herrington, William, MRCP
  • Mafham, Marion, MD
  • Majoni, William, FRACP
  • Wallendszus, Karl, MSc
  • Grimm, Richard, Prof
  • Pedersen, Terje, Prof
  • Tobert, Jonathan, PhD
  • Armitage, Jane, Prof
  • Baxter, Alex, BA
  • Bray, Christopher, PhD
  • Chen, Yiping, DPhil
  • Chen, Zhengming, Prof
  • Hill, Michael, DPhil
  • Knott, Carol, MSc
  • Parish, Sarah, DPhil
  • Simpson, David
  • Sleight, Peter, Prof
  • Young, Alan, DPhil
  • Collins, Rory, Prof
subjects:
  • Adult
  • Aged
  • Azetidines
  • Azetidines - administration & dosage
  • Basic Medicine
  • Biological and medical sciences
  • Blind Method
  • Blood pressure
  • Cancer
  • Cardiac arrhythmia
  • Cardiovascular disease
  • Cardiovascular Diseases
  • Cardiovascular Diseases - prevention & control
  • CARDIOVASCULAR EVENTS
  • Cholesterol
  • Cholesterol, LDL - analysis
  • Cholesterol, LDL - drug effects
  • Chronic
  • Combination
  • Compliance
  • Confidence Intervals
  • councils
  • DESIGN
  • Diagnosis
  • Dialysis
  • Dose
  • Dose-Response Relationship, Drug
  • Double
  • Double-Blind Method
  • Drug
  • Drug Administration Schedule
  • Drug Therapy
  • Drug Therapy, Combination
  • EFFICACY
  • Ezetimibe
  • Family medical history
  • Farmaceutiska vetenskaper
  • FARMACI
  • Fast track
  • Fast track — Articles
  • Female
  • Follow
  • Follow-Up Studies
  • General aspects
  • Health aspects
  • Heart failure
  • HEMODIALYSIS
  • Hospitals
  • Humans
  • Hypolipidemic Agents
  • Hypolipidemic Agents - administration & dosage
  • Hypolipidemic Agents - adverse effects
  • Internal Medicine
  • Kidney
  • Kidney diseases
  • Kidney Function Tests
  • Kidneys
  • Low density lipoproteins
  • Male
  • Medical and Health Sciences
  • Medical imaging
  • medical research
  • Medical sciences
  • Medicin och hälsovetenskap
  • Medicinska och farmaceutiska grundvetenskaper
  • METAANALYSIS
  • Middle Aged
  • Mortality
  • myocardial infarction
  • Nephrology. Urinary tract diseases
  • Nephropathies. Renovascular diseases. Renal failure
  • OUTCOMES
  • PARTICIPANTS
  • Pharmaceutical Sciences
  • PHARMACY
  • Physiological aspects
  • Reference Values
  • Renal Dialysis
  • Renal Dialysis - methods
  • Renal Dialysis - mortality
  • Renal failure
  • Renal Insufficiency
  • Renal Insufficiency, Chronic - diagnosis
  • Renal Insufficiency, Chronic - drug therapy
  • Renal Insufficiency, Chronic - mortality
  • Renal Insufficiency, Chronic - therapy
  • REQUIRING PROLONGED OBSERVATION
  • Response Relationship
  • Risk Assessment
  • SAFETY
  • Severity of Illness Index
  • Simvastatin
  • Simvastatin - administration & dosage
  • Simvastatin - adverse effects
  • stroke
  • Studies
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • UMCG Approved
  • UNITED-KINGDOM HEART
  • Up Studies
  • Urinary system involvement in other diseases. Miscellaneous
ispartof: Lancet, 2011, Vol.377 (9784), p.2181-2192
description: Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
  • 1474-547X
url: Link


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titleThe effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
sourceAlma/SFX Local Collection
creatorBaigent, Colin, Prof ; Landray, Martin J, FRCP ; Reith, Christina, MRCP ; Emberson, Jonathan, PhD ; Wheeler, David C, FRCP ; Tomson, Charles, DM ; Wanner, Christoph, Prof ; Krane, Vera, MD ; Cass, Alan, Prof ; Craig, Jonathan, Prof ; Neal, Bruce, Prof ; Jiang, Lixin, MD ; Hooi, Lai Seong, FRCP ; Levin, Adeera, Prof ; Agodoa, Lawrence, Prof ; Gaziano, Mike, Prof ; Kasiske, Bertram, Prof ; Walker, Robert, Prof ; Massy, Ziad A, Prof ; Feldt-Rasmussen, Bo, Prof ; Krairittichai, Udom, MD ; Ophascharoensuk, Vuddidhej, MD ; Fellström, Bengt, Prof ; Holdaas, Hallvard, MD ; Tesar, Vladimir, Prof ; Wiecek, Andrzej, Prof ; Grobbee, Diederick, Prof ; de Zeeuw, Dick, Prof ; Grönhagen-Riska, Carola, Prof ; Dasgupta, Tanaji, MRCP ; Lewis, David, MRCP ; Herrington, William, MRCP ; Mafham, Marion, MD ; Majoni, William, FRACP ; Wallendszus, Karl, MSc ; Grimm, Richard, Prof ; Pedersen, Terje, Prof ; Tobert, Jonathan, PhD ; Armitage, Jane, Prof ; Baxter, Alex, BA ; Bray, Christopher, PhD ; Chen, Yiping, DPhil ; Chen, Zhengming, Prof ; Hill, Michael, DPhil ; Knott, Carol, MSc ; Parish, Sarah, DPhil ; Simpson, David ; Sleight, Peter, Prof ; Young, Alan, DPhil ; Collins, Rory, Prof
creatorcontribBaigent, Colin, Prof ; Landray, Martin J, FRCP ; Reith, Christina, MRCP ; Emberson, Jonathan, PhD ; Wheeler, David C, FRCP ; Tomson, Charles, DM ; Wanner, Christoph, Prof ; Krane, Vera, MD ; Cass, Alan, Prof ; Craig, Jonathan, Prof ; Neal, Bruce, Prof ; Jiang, Lixin, MD ; Hooi, Lai Seong, FRCP ; Levin, Adeera, Prof ; Agodoa, Lawrence, Prof ; Gaziano, Mike, Prof ; Kasiske, Bertram, Prof ; Walker, Robert, Prof ; Massy, Ziad A, Prof ; Feldt-Rasmussen, Bo, Prof ; Krairittichai, Udom, MD ; Ophascharoensuk, Vuddidhej, MD ; Fellström, Bengt, Prof ; Holdaas, Hallvard, MD ; Tesar, Vladimir, Prof ; Wiecek, Andrzej, Prof ; Grobbee, Diederick, Prof ; de Zeeuw, Dick, Prof ; Grönhagen-Riska, Carola, Prof ; Dasgupta, Tanaji, MRCP ; Lewis, David, MRCP ; Herrington, William, MRCP ; Mafham, Marion, MD ; Majoni, William, FRACP ; Wallendszus, Karl, MSc ; Grimm, Richard, Prof ; Pedersen, Terje, Prof ; Tobert, Jonathan, PhD ; Armitage, Jane, Prof ; Baxter, Alex, BA ; Bray, Christopher, PhD ; Chen, Yiping, DPhil ; Chen, Zhengming, Prof ; Hill, Michael, DPhil ; Knott, Carol, MSc ; Parish, Sarah, DPhil ; Simpson, David ; Sleight, Peter, Prof ; Young, Alan, DPhil ; Collins, Rory, Prof ; on behalf of the SHARP Investigators ; SHARP Investigators
descriptionSummary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
identifier
0ISSN: 0140-6736
1ISSN: 1474-547X
2EISSN: 1474-547X
3DOI: 10.1016/S0140-6736(11)60739-3
4PMID: 21663949
5CODEN: LANCAO
languageeng
publisherKidlington: Elsevier Ltd
subjectAdult ; Aged ; Azetidines ; Azetidines - administration & dosage ; Basic Medicine ; Biological and medical sciences ; Blind Method ; Blood pressure ; Cancer ; Cardiac arrhythmia ; Cardiovascular disease ; Cardiovascular Diseases ; Cardiovascular Diseases - prevention & control ; CARDIOVASCULAR EVENTS ; Cholesterol ; Cholesterol, LDL - analysis ; Cholesterol, LDL - drug effects ; Chronic ; Combination ; Compliance ; Confidence Intervals ; councils ; DESIGN ; Diagnosis ; Dialysis ; Dose ; Dose-Response Relationship, Drug ; Double ; Double-Blind Method ; Drug ; Drug Administration Schedule ; Drug Therapy ; Drug Therapy, Combination ; EFFICACY ; Ezetimibe ; Family medical history ; Farmaceutiska vetenskaper ; FARMACI ; Fast track ; Fast track — Articles ; Female ; Follow ; Follow-Up Studies ; General aspects ; Health aspects ; Heart failure ; HEMODIALYSIS ; Hospitals ; Humans ; Hypolipidemic Agents ; Hypolipidemic Agents - administration & dosage ; Hypolipidemic Agents - adverse effects ; Internal Medicine ; Kidney ; Kidney diseases ; Kidney Function Tests ; Kidneys ; Low density lipoproteins ; Male ; Medical and Health Sciences ; Medical imaging ; medical research ; Medical sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; METAANALYSIS ; Middle Aged ; Mortality ; myocardial infarction ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; OUTCOMES ; PARTICIPANTS ; Pharmaceutical Sciences ; PHARMACY ; Physiological aspects ; Reference Values ; Renal Dialysis ; Renal Dialysis - methods ; Renal Dialysis - mortality ; Renal failure ; Renal Insufficiency ; Renal Insufficiency, Chronic - diagnosis ; Renal Insufficiency, Chronic - drug therapy ; Renal Insufficiency, Chronic - mortality ; Renal Insufficiency, Chronic - therapy ; REQUIRING PROLONGED OBSERVATION ; Response Relationship ; Risk Assessment ; SAFETY ; Severity of Illness Index ; Simvastatin ; Simvastatin - administration & dosage ; Simvastatin - adverse effects ; stroke ; Studies ; Survival Analysis ; Time Factors ; Treatment Outcome ; UMCG Approved ; UNITED-KINGDOM HEART ; Up Studies ; Urinary system involvement in other diseases. Miscellaneous
ispartofLancet, 2011, Vol.377 (9784), p.2181-2192
rights
0Elsevier Ltd
12011 Elsevier Ltd
2info:eu-repo/semantics/restrictedAccess
32015 INIST-CNRS
4Copyright © 2011 Elsevier Ltd. All rights reserved.
5COPYRIGHT 2011 Elsevier B.V.
6Copyright Elsevier Limited Jun 25-Jul 1, 2011
72011 Elsevier Ltd. All rights reserved. 2011 Elsevier Ltd
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1939t-60bb22b76b8a50ead2493b23caeb20c89773a5d2e5ce865052ca29a872169a583
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creatorcontrib
0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
27de Zeeuw, Dick, Prof
28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
50on behalf of the SHARP Investigators
51SHARP Investigators
title
0The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
1Lancet
addtitleLancet
descriptionSummary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
subject
0Adult
1Aged
2Azetidines
3Azetidines - administration & dosage
4Basic Medicine
5Biological and medical sciences
6Blind Method
7Blood pressure
8Cancer
9Cardiac arrhythmia
10Cardiovascular disease
11Cardiovascular Diseases
12Cardiovascular Diseases - prevention & control
13CARDIOVASCULAR EVENTS
14Cholesterol
15Cholesterol, LDL - analysis
16Cholesterol, LDL - drug effects
17Chronic
18Combination
19Compliance
20Confidence Intervals
21councils
22DESIGN
23Diagnosis
24Dialysis
25Dose
26Dose-Response Relationship, Drug
27Double
28Double-Blind Method
29Drug
30Drug Administration Schedule
31Drug Therapy
32Drug Therapy, Combination
33EFFICACY
34Ezetimibe
35Family medical history
36Farmaceutiska vetenskaper
37FARMACI
38Fast track
39Fast track — Articles
40Female
41Follow
42Follow-Up Studies
43General aspects
44Health aspects
45Heart failure
46HEMODIALYSIS
47Hospitals
48Humans
49Hypolipidemic Agents
50Hypolipidemic Agents - administration & dosage
51Hypolipidemic Agents - adverse effects
52Internal Medicine
53Kidney
54Kidney diseases
55Kidney Function Tests
56Kidneys
57Low density lipoproteins
58Male
59Medical and Health Sciences
60Medical imaging
61medical research
62Medical sciences
63Medicin och hälsovetenskap
64Medicinska och farmaceutiska grundvetenskaper
65METAANALYSIS
66Middle Aged
67Mortality
68myocardial infarction
69Nephrology. Urinary tract diseases
70Nephropathies. Renovascular diseases. Renal failure
71OUTCOMES
72PARTICIPANTS
73Pharmaceutical Sciences
74PHARMACY
75Physiological aspects
76Reference Values
77Renal Dialysis
78Renal Dialysis - methods
79Renal Dialysis - mortality
80Renal failure
81Renal Insufficiency
82Renal Insufficiency, Chronic - diagnosis
83Renal Insufficiency, Chronic - drug therapy
84Renal Insufficiency, Chronic - mortality
85Renal Insufficiency, Chronic - therapy
86REQUIRING PROLONGED OBSERVATION
87Response Relationship
88Risk Assessment
89SAFETY
90Severity of Illness Index
91Simvastatin
92Simvastatin - administration & dosage
93Simvastatin - adverse effects
94stroke
95Studies
96Survival Analysis
97Time Factors
98Treatment Outcome
99UMCG Approved
100UNITED-KINGDOM HEART
101Up Studies
102Urinary system involvement in other diseases. Miscellaneous
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startdate2011
enddate2011
creator
0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
27de Zeeuw, Dick, Prof
28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
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titleThe effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
authorBaigent, Colin, Prof ; Landray, Martin J, FRCP ; Reith, Christina, MRCP ; Emberson, Jonathan, PhD ; Wheeler, David C, FRCP ; Tomson, Charles, DM ; Wanner, Christoph, Prof ; Krane, Vera, MD ; Cass, Alan, Prof ; Craig, Jonathan, Prof ; Neal, Bruce, Prof ; Jiang, Lixin, MD ; Hooi, Lai Seong, FRCP ; Levin, Adeera, Prof ; Agodoa, Lawrence, Prof ; Gaziano, Mike, Prof ; Kasiske, Bertram, Prof ; Walker, Robert, Prof ; Massy, Ziad A, Prof ; Feldt-Rasmussen, Bo, Prof ; Krairittichai, Udom, MD ; Ophascharoensuk, Vuddidhej, MD ; Fellström, Bengt, Prof ; Holdaas, Hallvard, MD ; Tesar, Vladimir, Prof ; Wiecek, Andrzej, Prof ; Grobbee, Diederick, Prof ; de Zeeuw, Dick, Prof ; Grönhagen-Riska, Carola, Prof ; Dasgupta, Tanaji, MRCP ; Lewis, David, MRCP ; Herrington, William, MRCP ; Mafham, Marion, MD ; Majoni, William, FRACP ; Wallendszus, Karl, MSc ; Grimm, Richard, Prof ; Pedersen, Terje, Prof ; Tobert, Jonathan, PhD ; Armitage, Jane, Prof ; Baxter, Alex, BA ; Bray, Christopher, PhD ; Chen, Yiping, DPhil ; Chen, Zhengming, Prof ; Hill, Michael, DPhil ; Knott, Carol, MSc ; Parish, Sarah, DPhil ; Simpson, David ; Sleight, Peter, Prof ; Young, Alan, DPhil ; Collins, Rory, Prof
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languageeng
creationdate2011
topic
0Adult
1Aged
2Azetidines
3Azetidines - administration & dosage
4Basic Medicine
5Biological and medical sciences
6Blind Method
7Blood pressure
8Cancer
9Cardiac arrhythmia
10Cardiovascular disease
11Cardiovascular Diseases
12Cardiovascular Diseases - prevention & control
13CARDIOVASCULAR EVENTS
14Cholesterol
15Cholesterol, LDL - analysis
16Cholesterol, LDL - drug effects
17Chronic
18Combination
19Compliance
20Confidence Intervals
21councils
22DESIGN
23Diagnosis
24Dialysis
25Dose
26Dose-Response Relationship, Drug
27Double
28Double-Blind Method
29Drug
30Drug Administration Schedule
31Drug Therapy
32Drug Therapy, Combination
33EFFICACY
34Ezetimibe
35Family medical history
36Farmaceutiska vetenskaper
37FARMACI
38Fast track
39Fast track — Articles
40Female
41Follow
42Follow-Up Studies
43General aspects
44Health aspects
45Heart failure
46HEMODIALYSIS
47Hospitals
48Humans
49Hypolipidemic Agents
50Hypolipidemic Agents - administration & dosage
51Hypolipidemic Agents - adverse effects
52Internal Medicine
53Kidney
54Kidney diseases
55Kidney Function Tests
56Kidneys
57Low density lipoproteins
58Male
59Medical and Health Sciences
60Medical imaging
61medical research
62Medical sciences
63Medicin och hälsovetenskap
64Medicinska och farmaceutiska grundvetenskaper
65METAANALYSIS
66Middle Aged
67Mortality
68myocardial infarction
69Nephrology. Urinary tract diseases
70Nephropathies. Renovascular diseases. Renal failure
71OUTCOMES
72PARTICIPANTS
73Pharmaceutical Sciences
74PHARMACY
75Physiological aspects
76Reference Values
77Renal Dialysis
78Renal Dialysis - methods
79Renal Dialysis - mortality
80Renal failure
81Renal Insufficiency
82Renal Insufficiency, Chronic - diagnosis
83Renal Insufficiency, Chronic - drug therapy
84Renal Insufficiency, Chronic - mortality
85Renal Insufficiency, Chronic - therapy
86REQUIRING PROLONGED OBSERVATION
87Response Relationship
88Risk Assessment
89SAFETY
90Severity of Illness Index
91Simvastatin
92Simvastatin - administration & dosage
93Simvastatin - adverse effects
94stroke
95Studies
96Survival Analysis
97Time Factors
98Treatment Outcome
99UMCG Approved
100UNITED-KINGDOM HEART
101Up Studies
102Urinary system involvement in other diseases. Miscellaneous
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0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
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28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
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51SHARP Investigators
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au
0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
27de Zeeuw, Dick, Prof
28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
aucorp
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formatjournal
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ristypeJOUR
atitleThe effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
jtitleLancet
addtitleLancet
date2011
risdate2011
volume377
issue9784
spage2181
epage2192
pages2181-2192
issn
00140-6736
11474-547X
eissn1474-547X
codenLANCAO
notesCollaborators listed in the online webappendix
abstractSummary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
copKidlington
pubElsevier Ltd
pmid21663949
doi10.1016/S0140-6736(11)60739-3
oafree_for_read