SHARP
Trial question
What is the role of simvastatin plus ezetimibe in patients with advanced CKD?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 9270
9270 patients (3470 female, 5800 male).
Inclusion criteria: patients with advanced CKD.
Key exclusion criteria: history of MI or coronary revascularization procedure, history of chronic liver disease, active inflammatory muscle disease, previous adverse reaction to a statin or to ezetimibe, concurrent treatment with a contraindicated drug, or child-bearing potential.
Interventions
N=4650 simvastatin plus ezetimibe (20 mg simvastatin and 10 mg ezetimibe daily).
N=4620 placebo (matching placebo daily).
Primary outcome
Major atherosclerotic events
11.3%
13.4%
13.4 %
10.1 %
6.7 %
3.4 %
0.0 %
Simvastatin plus
ezetimibe
Placebo
Significant
decrease ▼
NNT = 47
Significant decrease in major atherosclerotic events (11.3% vs. 13.4%; RR 0.83, 95% CI 0.74 to 0.94).
Secondary outcomes
No significant difference in nonfatal MI or death from coronary artery disease (4.6% vs. 5%; RR 0.92, 95% CI 0.76 to 1.11).
Significant decrease in non-hemorrhagic stroke (2.8% vs. 3.8%; RR 0.75, 95% CI 0.6 to 0.94).
Significant decrease in arterial revascularisation procedures (6.1% vs. 7.6%; RR 0.79, 95% CI 0.68 to 0.93).
Safety outcomes
No significant differences in excess risk of myopathy (0.2% vs. 0.1%), hepatitis (0.5% vs. 0.4%) gallstones (2.3% vs. 2.3%), or cancer (9.4% vs. 9.5%, p=0.89), or excess of death from any non-vascular cause (14.4% vs. 13.2%, p=0.13).
Conclusion
In patients with advanced CKD, simvastatin plus ezetimibe was superior to placebo with respect to major atherosclerotic events.
Reference
Baigent C, Landray MJ, Reith C et al. 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(9784):2181-92.
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