23967
document
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 . 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 .
23968
Intervention_Pharmacological
pioglitazone
23969
Intervention_Pharmacological
oral pioglitazone titrated from 15 mg to 45 mg
23970
Intervention_Control
matching placebo
23971
Intervention_Pharmacological
glucose-lowering drugs
23972
Outcome_Physical
macrovascular events
23973
Outcome_Physical
myocardial infarction
23974
Outcome_Physical
stroke
23975
Outcome_Physical
macrovascular complications
23976
Outcome_Physical
macrovascular morbidity
23977
Outcome_Mortality
mortality
23978
Outcome_Physical
macrovascular disease
23979
Outcome_Mortality
composite of all-cause mortality
23980
Outcome_Physical
non fatal myocardial infarction
23981
Outcome_Physical
silent myocardial infarction
23982
Outcome_Physical
stroke
23983
Outcome_Physical
acute coronary syndrome
23984
Outcome_Physical
endovascular or surgical intervention in the coronary or leg arteries
23985
Outcome_Physical
amputation above the ankle
23986
Outcome_Physical
primary composite endpoint
23987
Outcome_Mortality
composite of all-cause mortality
23988
Outcome_Physical
, non-fatal myocardial infarction , and stroke
23989
Outcome_Physical
endpoint
23990
Outcome_Other
Overall safety
23991
Outcome_Other
tolerability
23992
Outcome_Other
safety
23993
Outcome_Physical
heart failure
23994
Outcome_Mortality
mortality rates from heart failure
23995
Outcome_Mortality
mortality
23996
Outcome_Physical
non-fatal myocardial infarction
23997
Outcome_Physical
stroke
23998
Participant_Condition
type 2 diabetes
23999
Participant_Condition
type 2 diabetes
24000
Participant_Condition
type 2 diabetes
24001
Participant_Sample-size
5238
24002
Participant_Condition
type 2 diabetes
24003
Participant_Condition
macrovascular disease
24004
Participant_Sample-size
514
24005
Participant_Sample-size
2605
24006
Participant_Condition
type 2 diabetes
24007
Participant_Condition
macrovascular events