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
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, Fellström B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Grönhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R, SHARP Investigators
Lancet (London, England) · 1,746 citas
Etiquetas de revisión
Financiado por la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Organización sin fines de lucro
- British Heart Foundation
- Gobierno
- Medical Research Council
- Gobierno
- National Health and Medical Research Council
- Gobierno
- National Medical Research Council
- Subvenciones
- British Heart Foundation (RE/08/04); Medical Research Council (MC_EX_G0801669)
Según 4 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2011-06-01 · Lancet · vol. 377 · número 9784 · págs. 2181–2192
- Editorial
- Elsevier BV
- Citado
- 2,477 citas · más que el 100% de estudios similares · 249.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 28 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Chronic Kidney Disease and Diabetes · Blood Pressure and Hypertension Studies
- Palabras clave
- simvastatin, ezetimibe, LDL cholesterol lowering, chronic kidney disease, dialysis, myocardial infarction, stroke, coronary artery disease, cardiovascular risk reduction, SHARP trial, cardiovascular mortality, cardiovascular risk stratification
- MeSH
- humans, cardiovascular diseases, azetidines, simvastatin, kidney function tests, treatment outcome, drug therapy, combination, renal dialysis, drug administration schedule, severity of illness index, confidence intervals, risk assessment, survival analysis, follow-up studies, double-blind method, dose-response relationship, drug, time factors, reference values, adult, aged, middle aged, female, male, renal insufficiency, chronic, cholesterol, ldl, hypolipidemic agents, ezetimibe
50 autores
- Colin Baigent🇬🇧 · autor de correspondenciaUniversity of Oxford
- Martin Landray🇬🇧University of Oxford
- Christina A. Reith🇬🇧University of Oxford
- Jonathan Emberson🇬🇧University of Oxford
- David Collins. Wheeler🇬🇧University College London
- Charles Tomson🇬🇧North Bristol NHS Trust
- Christoph Wanner🇩🇪University of Würzburg
- Vera Krane🇩🇪University of Würzburg
- Alan Cass🇦🇺The University of Sydney; The George Institute for Global Health
- Jonathan C. Craig🇦🇺The University of Sydney; Children's Hospital at Westmead
- Bruce Charles Neal🇦🇺The University of Sydney; The George Institute for Global Health
- Lixin Jiang🇨🇳Chinese Academy of Medical Sciences & Peking Union Medical College; Fu Wai Hospital
- Lai Seong Hooi🇲🇾Sultanah Aminah Hospital
- Adeera Levin🇨🇦University of British Columbia
- Lawrence Y C Agodoa🇺🇸National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
- Mike Gaziano🇺🇸Brigham and Women's Hospital; Harvard University
- B.L. Kasiske🇺🇸University of Minnesota
- Robert James Walker🇳🇿University of Otago
- Ziad A. Massy🇫🇷Inserm; Centre Hospitalier Universitaire Amiens-Picardie; Université de Picardie Jules Verne
- Bo Feldt‐Rasmussen🇩🇰University of Copenhagen; Rigshospitalet
- Udom Krairittichai🇹🇭Rajavithi Hospital
- Vuddhidej Ophascharoensuk🇹🇭Chiang Mai University
- Bengt Fellström🇸🇪Uppsala University Hospital
- Hallvard Holdaas🇳🇴Oslo University Hospital
- Vladimı́r Tesař🇨🇿Charles University; General University Hospital in Prague
- Andrzej Więcek🇵🇱Medical University of Silesia
- Diederick E. Grobbee🇳🇱Utrecht University; University Medical Center Utrecht
- Dick de Zeeuw🇳🇱University Medical Center Groningen
- Carola Grönhagen‐Riska🇫🇮Helsinki University Hospital
- Tanaji Dasgupta🇬🇧John Radcliffe Hospital
- David Lewis🇬🇧University of Oxford
- William Guy Herrington🇬🇧University of Oxford
- Marion Mafham🇬🇧University of Oxford
- William Majoni🇦🇺Royal Darwin Hospital
- Karl Wallendszus🇬🇧University of Oxford
- Richard H. Grimm🇺🇸University of Minnesota; Hennepin County Medical Center; Berman Center for Outcomes and Clinical Research
- Terje Pedersen🇳🇴Oslo University Hospital; University of Oslo
- Jonathan A. Tobert🇺🇸American Metal Processing (United States)
- Jane Armitage🇬🇧University of Oxford
- Alex Baxter🇬🇧University of Oxford
- Christopher Bray🇬🇧University of Oxford
- Yiping Chen🇬🇧University of Oxford
- Zhengming Chen🇬🇧University of Oxford
- Michael Hill🇬🇧University of Oxford
- Carol Knott🇬🇧University of Oxford
- Sarah Parish🇬🇧University of Oxford
- David Simpson🇬🇧University of Oxford
- Peter Sleight🇬🇧John Radcliffe Hospital; University of Oxford
- Alan Young🇬🇧University of Oxford
- Rory Collins🇬🇧University of Oxford
Resumen
El texto original del estudio, en el idioma en que se publicó.
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. The SHARP trial aimed to assess the efficacy 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 prespecified outcome was first 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 difference 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-significantly 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 significant 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-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed 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 significant 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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.