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Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial

BACKGROUND: Findings of large randomised trials have shown that lowering LDL cholesterol with statins reduces vascular morbidity and mortality rapidly, but limited evidence exists about the long-term efficacy and safety of statin treatment. The aim of the extended follow-up of the Heart Protection S...

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Autor principal: Heart Protection Study Collaborative Group
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lancet Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242163/
https://www.ncbi.nlm.nih.gov/pubmed/22115874
http://dx.doi.org/10.1016/S0140-6736(11)61125-2
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author Heart Protection Study Collaborative Group
author_facet Heart Protection Study Collaborative Group
author_sort Heart Protection Study Collaborative Group
collection PubMed
description BACKGROUND: Findings of large randomised trials have shown that lowering LDL cholesterol with statins reduces vascular morbidity and mortality rapidly, but limited evidence exists about the long-term efficacy and safety of statin treatment. The aim of the extended follow-up of the Heart Protection Study (HPS) is to assess long-term efficacy and safety of lowering LDL cholesterol with statins, and here we report cause-specific mortality and major morbidity in the in-trial and post-trial periods. METHODS: 20 536 patients at high risk of vascular and non-vascular outcomes were allocated either 40 mg simvastatin daily or placebo, using minimised randomisation. Mean in-trial follow-up was 5·3 years (SD 1·2), and post-trial follow-up of surviving patients yielded a mean total duration of 11·0 years (SD 0·6). The primary outcome of the long-term follow-up of HPS was first post-randomisation major vascular event, and analysis was by intention to treat. This trial is registered with ISRCTN, number 48489393. FINDINGS: During the in-trial period, allocation to simvastatin yielded an average reduction in LDL cholesterol of 1·0 mmol/L and a proportional decrease in major vascular events of 23% (95% CI 19–28; p<0·0001), with significant divergence each year after the first. During the post-trial period (when statin use and lipid concentrations were similar in both groups), no further significant reductions were noted in either major vascular events (risk ratio [RR] 0·95 [0·89–1·02]) or vascular mortality (0·98 [0·90–1·07]). During the combined in-trial and post-trial periods, no significant differences were recorded in cancer incidence at all sites (0·98 [0·92–1·05]) or any particular site, or in mortality attributed to cancer (1·01 [0·92–1·11]) or to non-vascular causes (0·96 [0·89–1·03]). INTERPRETATION: More prolonged LDL-lowering statin treatment produces larger absolute reductions in vascular events. Moreover, even after study treatment stopped in HPS, benefits persisted for at least 5 years without any evidence of emerging hazards. These findings provide further support for the prompt initiation and long-term continuation of statin treatment. FUNDING: UK Medical Research Council, British Heart Foundation, Merck & Co, Roche Vitamins.
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spelling pubmed-32421632011-12-28 Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial Heart Protection Study Collaborative Group Lancet Articles BACKGROUND: Findings of large randomised trials have shown that lowering LDL cholesterol with statins reduces vascular morbidity and mortality rapidly, but limited evidence exists about the long-term efficacy and safety of statin treatment. The aim of the extended follow-up of the Heart Protection Study (HPS) is to assess long-term efficacy and safety of lowering LDL cholesterol with statins, and here we report cause-specific mortality and major morbidity in the in-trial and post-trial periods. METHODS: 20 536 patients at high risk of vascular and non-vascular outcomes were allocated either 40 mg simvastatin daily or placebo, using minimised randomisation. Mean in-trial follow-up was 5·3 years (SD 1·2), and post-trial follow-up of surviving patients yielded a mean total duration of 11·0 years (SD 0·6). The primary outcome of the long-term follow-up of HPS was first post-randomisation major vascular event, and analysis was by intention to treat. This trial is registered with ISRCTN, number 48489393. FINDINGS: During the in-trial period, allocation to simvastatin yielded an average reduction in LDL cholesterol of 1·0 mmol/L and a proportional decrease in major vascular events of 23% (95% CI 19–28; p<0·0001), with significant divergence each year after the first. During the post-trial period (when statin use and lipid concentrations were similar in both groups), no further significant reductions were noted in either major vascular events (risk ratio [RR] 0·95 [0·89–1·02]) or vascular mortality (0·98 [0·90–1·07]). During the combined in-trial and post-trial periods, no significant differences were recorded in cancer incidence at all sites (0·98 [0·92–1·05]) or any particular site, or in mortality attributed to cancer (1·01 [0·92–1·11]) or to non-vascular causes (0·96 [0·89–1·03]). INTERPRETATION: More prolonged LDL-lowering statin treatment produces larger absolute reductions in vascular events. Moreover, even after study treatment stopped in HPS, benefits persisted for at least 5 years without any evidence of emerging hazards. These findings provide further support for the prompt initiation and long-term continuation of statin treatment. FUNDING: UK Medical Research Council, British Heart Foundation, Merck & Co, Roche Vitamins. Lancet Publishing Group 2011-12-10 /pmc/articles/PMC3242163/ /pubmed/22115874 http://dx.doi.org/10.1016/S0140-6736(11)61125-2 Text en © 2011 Elsevier Ltd. All rights reserved. This document may be redistributed and reused, subject to certain conditions (http://www.elsevier.com/wps/find/authorsview.authors/supplementalterms1.0) .
spellingShingle Articles
Heart Protection Study Collaborative Group
Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
title Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
title_full Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
title_fullStr Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
title_full_unstemmed Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
title_short Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
title_sort effects on 11-year mortality and morbidity of lowering ldl cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242163/
https://www.ncbi.nlm.nih.gov/pubmed/22115874
http://dx.doi.org/10.1016/S0140-6736(11)61125-2
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