| Authors |
| Baigent C, Landray MJ, Reith C, et al. |
| Title |
| The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) |
| References |
| Lancet. 2011 Jun 25;377(9784):2181-92 |
| 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. |
| Purpose |
| The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in people with moderate-to-severe kidney disease. |
| Design |
- Multicenter, randomized, double-blind, controlled trial
- 9270 patients aged >40 years with chronic kidney disease (Cr >150 umol/L men; >130 umol/L women)
- 3023 on dialysis; 6247 not
|
| Exclusion Criteria |
- History of myocardial infarction or coronary revascularization
- Renal transplant
- <2 month. from uremic emergency
- Liver function tests >1.5x ULN
- CK >3x ULN
- Other serious medication condition
- Concurrent use of contraindicated medication (i.e. statin, ezetimibe, cyclosporine)
|
| Follow-Up |
| Median 4.9 years |
| Treatment Regimen |
- Simvastatin 20mg/day + ezetimibe 10mg/day, simastatin 20mg/day (for 1st year, then ezetimibe added) or placebo
- Clinical assessment at 2. 6. 12 months after randomization and then every 6 months thereafter
- Compliance and blood work assessed at each visit
|
| Results |
Placebo
n=4620 | Simva + ezetimibe
n=4650 | Hazard Ratio | p |
|---|
| Composite of cardiac death, nonfatal myocardial infarction, coronary revascularization and stroke |
|---|
| 13.4% | 11.3% | 0.83 (0.74-0.94) | 0.0021 | | Cardiac death |
|---|
| 1.9% | 2.0% | 1.01 (0.75-1.35) | 0.95 | | Non-fatal myocardial infarction |
|---|
| 3.4% | 2.9% | 0.84 (0.65-1.05) | 0.12 | | Ischemic stroke |
|---|
| 3.8% | 2.8% | 0.75 (0.60-0.94) | 0.01 | | Revascularization |
|---|
| 7.6% | 6.1% | 0.79 (0.68-0.93) | 0.0036 | |
| Summary |
| Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events (stroke and revascularization) in a wide range of patients with advanced chronic kidney disease. |