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

Baigent, Colin, Landray, Martin J., Reith, Christina, Emberson, Jonathan, Wheeler, David C., Tomson, Charles, Wanner, Christoph, Krane, Vera, Cass, Alan, Craig, Jonathan, Neal, Bruce, Jiang, Neal, Lixin, Hooi, Lai Seong, Levin, Adeera, Agodoa, Lawrence, Gaziano, Mike, Kasiske, Bertram, Walker, Robert, Massy, Ziad A., Feldt-Rasmussen, Bo, Krairittichai, Udon, Ophascharoensuk, Vuddidhej, Fellstrom, Bengt, Holdaas, Hallvard, Tesar, Viadimir, Wiecek, Andrzej, Grobbee, Diederick, de Zeeuw, Dick, Gronhagen-Riska, Carola, Dasgupta, Tanaji, Lewis, David, Herrington, William, Mafham, Marion, Majoni, William, Wallendszus, Karl, Grimm, Richard, Pedersen, Terje, Tobert, Jonathan, Armitage, Jane, Baxter, Alex, Bray, Christopher, Chen, Yiping, Chen, Zhengming, Hill, Michael, Knott, Carol, Parish, Sarah, Simpson, David, Sleight, Peter, Young, Alan, Collins, Roy, on behalf of the SHARP Investigators and Mudge, D. (2011) 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. Lancet, 377 9784: 2181-2192. doi:10.1016/S0140-6736(11)60739-3

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Author Baigent, Colin
Landray, Martin J.
Reith, Christina
Emberson, Jonathan
Wheeler, David C.
Tomson, Charles
Wanner, Christoph
Krane, Vera
Cass, Alan
Craig, Jonathan
Neal, Bruce
Jiang, Neal, Lixin
Hooi, Lai Seong
Levin, Adeera
Agodoa, Lawrence
Gaziano, Mike
Kasiske, Bertram
Walker, Robert
Massy, Ziad A.
Feldt-Rasmussen, Bo
Krairittichai, Udon
Ophascharoensuk, Vuddidhej
Fellstrom, Bengt
Holdaas, Hallvard
Tesar, Viadimir
Wiecek, Andrzej
Grobbee, Diederick
de Zeeuw, Dick
Gronhagen-Riska, Carola
Dasgupta, Tanaji
Lewis, David
Herrington, William
Mafham, Marion
Majoni, William
Wallendszus, Karl
Grimm, Richard
Pedersen, Terje
Tobert, Jonathan
Armitage, Jane
Baxter, Alex
Bray, Christopher
Chen, Yiping
Chen, Zhengming
Hill, Michael
Knott, Carol
Parish, Sarah
Simpson, David
Sleight, Peter
Young, Alan
Collins, Roy
on behalf of the SHARP Investigators
Mudge, D.
Total Author Count Override 50
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
Journal name Lancet   Check publisher's open access policy
ISSN 0140-6736
Publication date 2011-06
Sub-type Article (original research)
DOI 10.1016/S0140-6736(11)60739-3
Open Access Status
Volume 377
Issue 9784
Start page 2181
End page 2192
Total pages 12
Place of publication London, U.K.
Publisher The Lancet Publishing Group
Collection year 2012
Language eng
Formatted abstract
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 eff ects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the effi cacy and safety of the combination of simvastatin plus ezetimibe in such patients.


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 prespecifi ed 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, NCT00125593, and ISRCTN54137607.


4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol diff erence 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-signifi cantly 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 signifi cant 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-specifi c reductions in LDL cholesterol, there was no good evidence that the proportional eff ects on major
atherosclerotic events diff ered 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 signifi cant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13).


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.
Keyword Requiring Prolonged Observation
United-Kingdom Heart
Cardiovascular Events
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published Online 9 June 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
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Created: Mon, 20 Feb 2012, 13:09:38 EST by Dr David Mudge on behalf of School of Medicine