Document Detail


Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.
MedLine Citation:
PMID:  16214598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes.
METHODS: We did a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. We recruited patients from primary-care practices and hospitals. We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), to be taken in addition to their glucose-lowering drugs and other medications. Our primary endpoint was the composite of all-cause mortality, non fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN NCT00174993.
FINDINGS: Two patients were lost to follow-up, but were included in analyses. The average time of observation was 34.5 months. 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, and stroke. 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint (0.84, 0.72-0.98, p=0.027). Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified. 6% (149 of 2065) and 4% (108 of 2633) of those in the pioglitazone and placebo groups, respectively, were admitted to hospital with heart failure; mortality rates from heart failure did not differ between groups.
INTERPRETATION: Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events.
Authors:
John A Dormandy; Bernard Charbonnel; David J A Eckland; Erland Erdmann; Massimo Massi-Benedetti; Ian K Moules; Allan M Skene; Meng H Tan; Pierre J Lefèbvre; Gordon D Murray; Eberhard Standl; Robert G Wilcox; Lars Wilhelmsen; John Betteridge; Kåre Birkeland; Alain Golay; Robert J Heine; László Korányi; Markku Laakso; Marián Mokán; Antanas Norkus; Valdis Pirags; Toomas Podar; André Scheen; Werner Scherbaum; Guntram Schernthaner; Ole Schmitz; Jan Skrha; Ulf Smith; Jan Taton;
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  366     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-10-21     Revised Date:  2011-10-31    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1279-89     Citation Subset:  AIM; IM    
Affiliation:
Department of Clinical Vascular Research, Ingelby House, St Georges Hospital, Blackshaw Road, London SW17 0QT, UK. john.dormandy@btinternet.com
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00174993
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Coronary Disease / etiology,  prevention & control*
Diabetes Mellitus, Type 2 / complications,  drug therapy*
Female
Humans
Hypoglycemic Agents / therapeutic use*
Male
Middle Aged
Myocardial Infarction / etiology,  prevention & control*
PPAR gamma / agonists*
Risk Factors
Stroke / etiology,  prevention & control*
Thiazolidinediones / therapeutic use*
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 111025-46-8/pioglitazone
Comments/Corrections
Comment In:
Lancet. 2011 Oct 29;378(9802):1544; author reply 1544-5   [PMID:  22035551 ]
Lancet. 2011 Oct 29;378(9802):1543-4; author reply 1544-5   [PMID:  22035550 ]
Lancet. 2005 Oct 8;366(9493):1241-2   [PMID:  16214581 ]
Lancet. 2006 Jan 7;367(9504):23; author reply 26-7   [PMID:  16399141 ]
Lancet. 2006 Jan 7;367(9504):23; author reply 26-7   [PMID:  16399140 ]
Lancet. 2006 Jan 7;367(9504):23-4; author reply 26-7   [PMID:  16399142 ]
Lancet. 2006 Jan 7;367(9504):24-5; author reply 26-7   [PMID:  16399143 ]
Lancet. 2006 Jan 7;367(9504):25-6; author reply 26-7   [PMID:  16399144 ]
Lancet. 2006 Mar 25;367(9515):982   [PMID:  16564353 ]
ACP J Club. 2006 Mar-Apr;144(2):34   [PMID:  16539349 ]
Evid Based Med. 2006 Apr;11(2):47   [PMID:  17213077 ]
Curr Atheroscler Rep. 2007 Jan;9(1):45   [PMID:  17169244 ]

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