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Titolo The eff ects 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
Autore Colin Baigent, Martin J Landray, Christina Reith, Jonathan Emberson, David C Wheeler, Charles Tomson, Christoph Wanner, Vera Krane, Alan Cass, Jonathan Craig, Bruce Neal, Lixin Jiang, Lai Seong Hooi, Adeera Levin, Lawrence Agodoa, Mike Gaziano, Bertram Kasiske, Robert Walker, Ziad A Massy, Bo Feldt-Rasmussen, Udom Krairittichai, Vuddidhej Ophascharoensuk, Bengt Fellström, Hallvard Holdaas, Vladimir Tesar, Andrzej Wiecek, Diederick Grobbee, Dick de Zeeuw, Carola Grönhagen-Riska, Tanaji Dasgupta, David Lewis, William Herrington, Marion Ma_ am, William Majoni, Karl Wallendszus, Richard Grimm, Terje Pedersen, Jonathan Tobert, Jane Armitage, Alex Baxter, Christopher Bray, Yiping Chen, Zhengming Chen, Michael Hill, Carol Knott, Sarah Parish, David Simpson, Peter Sleight, Alan Young, Rory Collins, on behalf of the SHARP Investigators*
Referenza Lancet 2011; 377: 2181-92
Contenuto 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 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. Methods 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 fi rst 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 ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. Findings 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). Interpretation 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.
Data 14.07.2011
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