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Among patients with pre-existing coronary heart
disease (CHD), large-scale randomized trials have demonstrated
that lowering LDL-cholesterol concentration by about 1 mmol/l
(40 mg/dl) for 4-5 years reduces the risk of coronary events
and of strokes by about 25%. However, it is not known if LDL-cholesterol
lowering among chronic kidney disease (CKD) patients without
CHD would also reduce risks of CVD events. |
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Vasculopathic changes distinct from atherosclerosis (including
cardiomyopathy, arterial stiffness, and calcification) are highly
prevalent in chronic kidney disease (CKD) patients, and their
etiology may not be related to blood cholesterol. Observational
studies among dialysis patients have consistently failed to demonstrate
a positive relation between blood total cholesterol and mortality.
However, since CKD patients have systematically been excluded
from randomized, controlled clinical trials of cholesterol lowering,
the effect of lowering cholesterol in these patients is unknown. |
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The Study of Heart and Renal Protection (SHARP) will enroll approximately
9,000 participants from around the world, all with chronic kidney
disease, none with known CHD, and approximately 1/3 of them are
expected to be on dialysis. Participants will be randomized to
one of three treatment arms. Arm 1 is placebo only for five years.
Arm 2 is simvastatin-20mg daily and ezetimibe-10mg daily for
five years. Arm 3 is simvastatin-20mg daily for one year, after
which half will be randomized to Arm 1 and the other half randomized
to Arm 2. Thus by the end of the study, there are only two distinct
treatments. The primary endpoint will be “major vascular
event” during the five years (defined as non-fatal myocardial
infarction or cardiac death, non-fatal or fatal stroke, or revascularisation). |
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Participants are seen at the clinic for an initial screening
visit, a randomization visit, a 2-month and 6-month follow-up
visit, and then follow-up visits at six month intervals for at
least four years. At each visit, serious adverse events will
be recorded and a blood sample will be taken for local analysis
of liver transaminase, creatine kinase and creatinine. Central
laboratory assessment of lipid profiles will be taken at randomization
and at 2.5 years follow-up for all participants and from a random
10% subsample of patients at 1 and 4 years follow-up. |
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This study is sponsored by the University of Oxford, UK and funded by Merck Schering Plough. |
