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19 February 2009
Article (Scientific journals)
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
Dormandy, John A.; Charbonnel, Bernard; Eckland, David J. A. et al.
2005 • In Lancet, 366 (9493), p. 1279-1289
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Abstract :
[en] 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.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Dormandy, John A.;  St Georges Hospital (London) > Ingelby House > Department of Clinical Vascular Research
Charbonnel, Bernard;  Hôtel Dieu (Nantes) > Clinique d'Endocrinologie
Eckland, David J. A.
Erdmann, Erland;  University of Cologne > Klinik III für Innere Medizin
Massi-Benedetti, Massimo;  University of Perugia > Medicine and Metabolic Diseases
Kmoules, Ian K.;  Takeda Europe R&D Centre (London)
Skene, Allan M.;  Isaac Newton Centre > Nottingham Clinical Research Limited
Tan, Meng H.;  Lilly Corporate Center (Indianapolis, USA)
Lefèbvre, Pierre J.;  CHU SartTilman (Liège)
Murray, Gordon D.;  University of Edinburgh Medical School > Department of Public Health Sciences
Standl, Eberhard;  Munich Diabetes Research Institute
Wilcox, Robert G.;  University Hospital (Nottingham) > Department of Cardiovascular Medicine
Wihelmsen, Lars;  Göteborg University > Institute of Cardiovascular Medicine
Betteridge, John;  University College London > Department of Medicine
Birkeland, Kåre;  University of Oslo > Aker University Hospital > Research Centre
Golay, Alain;  Geneva University Hospital > Service for Therapeutic Education for Chronic Diseases
Heine, Robert J.;  University Medical Centre (Amsterdam)
Koranyi, László
Laakso, Markku;  Kuopio University Hospital (Finland) > Department of Medicine
Mokan, Marián;  Comenius University
Norkus, Antanas;  Kaunas University of Medicine (Lithuania) > Institute of Endocrinology
Pirags, Valdis;  Paula Strandina Kliniska Universitates Slimnica (Riga)
Podar, Toomas;  Endocrinology Centre (Tartu, Estonia)
Scheen, André  ;  Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Scherbaum, Werner;  University of Dusseldorf > German Diabetes Centre
Schernthaner, Guntram;  Rudolfstiftung Hospital (Vienna) > Department of Medicine
Schmitz, Ole;  University of Aarhus (Denmark) > Institute of Clinical Pharmacology
Skrha, Jan
Smith, Ulf;  University of Göteborg > Lundberg Laboratory for Diabetes Research
Taton, Jan;  Warsaw Medical University (Poland) > Department of Internal Medicine and Diabetology
More authors (20 more) Less
Language :
English
Title :
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
Publication date :
08 October 2005
Journal title :
Lancet
ISSN :
0140-6736
eISSN :
1474-547X
Publisher :
Lancet Ltd, London, United Kingdom
Volume :
366
Issue :
9493
Pages :
1279-1289
Peer reviewed :
Peer Reviewed verified by ORBi
Additional URL :
Commentary :
The Lancet, Volume 366, Issue 9493, 8 October 2005-14 October 2005, Pages 1279-1289

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