See also:

SHARP study, 2010	TRC8081
[NCT00125593]	download pdf: ezetimibe+simvastatin | cholesterol lowering intervention for cardiovascular prevention

Treatments

Studied treatment	Simvastatin 20mg/Ezetimibe 10mg
Control treatment	placebo
Remarks	3 arms: Simvastatin 20 mg, Simvastatin 20mg/Ezetimibe 10mg and placebo

Patients

Patients	patients with established chronic kidney disease (dialysis or pre-dialysis)
Inclusion criteria	history of chronic kidney disease (CKD): either patients who are pre-dialysis (with a plasma or serum creatinine greater than or equal to 150 micromol/l [greater than or equal to 1.7 mg/dl] in men, or greater than or equal to 130 micromol/l [greater than or equal to 1.5 mg/dl] in women) or patients on dialysis (haemodialysis or peritoneal dialysis); men or women aged greater than or equal to 40 years
Exclusion criteria	definite history of myocardial infarction or coronary revascularisation procedure; functioning renal transplant, or living donor-related transplant planned; less than 2 months since presentation as an acute uraemic emergency; definite history of chronic liver disease, or abnormal liver function (i.e. alanine aminotransferase [ALT] > 1.5 x upper limit of normal [ULN] or, if ALT not available, aspartate aminotransferase [AST] > 1.5 x ULN); evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatinine kinase (CK) >3 x ULN; definite previous adverse reaction to a statin or to ezetimibe; concurrent treatment with a contraindicated drug (HMG-CoA reductase inhibitor ("statin"); fibric acid derivative ("fibrate"); nicotinic acid; macrolide antibiotic (erythromycin, clarithromycin); systemic use of imidazole or triazole antifungals (e.g. itraconazole, ketoconazole); protease-inhibitors (e.g. antiretroviral drugs for HIV infection); nefazodone; ciclosporin); child-bearing potential; known to be poorly compliant with clinic visits or prescribed medication; medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease, history of cancer other than non-melanoma skin cancer, or recent history of alcohol or substance misuse)

Method and design

Randomized effectives	4193 / 4191 (studied vs. control)
Design	Parallel groups
Blinding	double-blind
Follow-up duration	4.9 years
Number of centre	300
Geographic area	20 countries
Hypothesis	Superiority
Primary endpoint	vascular events: cardiac death, MI, any stroke, or any revascularization
Remarks	There is a certain incertitude concerning the primary endpoint (apparently changed by the Steering committe before the trial ended but this change was not endorsed by the sponsor) Statistical analysis plan is not clear too, with or without the inclusion of patients initially allocated to simvastatin alone and re-randomized to either combination or placebo for the remainder of the study period

Results

Endpoint Studied treat.
n/N Control treat.
n/N Graph RR [95% CI]

Coronary event

213 / 4650
230 / 4620
0,92 [0,77;1,10]

End stage renal disease

1057 / 4650
1084 / 4620
0,97 [0,90;1,04]

Fatal stroke

68 / 4650
78 / 4620
0,87 [0,63;1,20]

All cause death

1142 / 4650
1115 / 4620
1,02 [0,95;1,09]

Cancer

438 / 4650
439 / 4620
0,99 [0,87;1,12]

cardiovascular events

710 / 4650
814 / 4620
0,87 [0,79;0,95] 0 2 1.0

Relative risks
Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
	Studied treat.	Control treat.
Coronary event	213 / 4650 (4,6%)	230 / 4620 (5,0%)	0,92	[0,77;1,10]
End stage renal disease	1057 / 4650 (22,7%)	1084 / 4620 (23,5%)	0,97	[0,90;1,04]
Fatal stroke	68 / 4650 (1,5%)	78 / 4620 (1,7%)	0,87	[0,63;1,20]
All cause death	1142 / 4650 (24,6%)	1115 / 4620 (24,1%)	1,02	[0,95;1,09]
Cancer	438 / 4650 (9,4%)	439 / 4620 (9,5%)	0,99	[0,87;1,12]	Any incident cancer
cardiovascular events	710 / 4650 (15,3%)	814 / 4620 (17,6%)	0,87	[0,79;0,95]	cardiac death, MI, any stroke, or any revascularization
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction:

Endpoint	studied treat.	control treat.	mean diff

Absolute risk reduction (for a follow-up of 4.9 years)
Endpoint	Events rate		Absolute risk reduction (ARR)
	Studied treat.	Control treat.
Coronary event	4,58%	4,98%	-0,40%
End stage renal disease	22,73%	23,46%	-0,73%
Fatal stroke	1,46%	1,69%	-0,23%
All cause death	24,56%	24,13%	0,42%
Cancer	9,42%	9,50%	-0,08%
cardiovascular events	15,27%	17,62%	-2,35%

Meta-analysis of all similar trials:

cholesterol lowering intervention in cardiovascular prevention for all chronical situations

cholesterol lowering intervention in cardiovascular prevention for patients with renal insufficiency (on hemodialysis or transplant)

Reference(s)

TrialResults-center ID	TRC8081
Trials register #	NCT00125593
Study web site link	http://www.ctsu.ox.ac.uk/~sharp/

• Sharp Collaborative Group. 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.. Am Heart J 2010 Nov;160:785-794.e10 - 10.1016/j.ahj.2010.08.012
  Pubmed | Hubmed | Fulltext
• Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellstr�m B. 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 2011 Jun 25;377:2181-2192 - 10.1016/S0140-6736(11)60739-3
  Pubmed | Hubmed | Fulltext

(c) 2004-2016 TrialResults-center - All Rights Reserved