PMID- 20923486
OWN - NLM
STAT- MEDLINE
DCOM- 20110202
LR  - 20181201
IS  - 1753-0407 (Electronic)
IS  - 1753-0407 (Linking)
VI  - 2
IP  - 3
DP  - 2010 Sep
TI  - Pioglitazone and the risk of cardiovascular events in patients with Type 2 
      diabetes receiving concomitant treatment with nitrates, renin-angiotensin system 
      blockers, or insulin: results from the PROactive study (PROactive 20).
PG  - 212-20
LID - 10.1111/j.1753-0407.2010.00082.x [doi]
AB  - BACKGROUND: Patients with Type 2 diabetes mellitus (T2DM) are often treated with 
      multiple glucose-lowering and cardiovascular agents. The concomitant use of 
      nitrates, renin-angiotensin system (RAS) blockers, or insulin has been linked to 
      a potential increase in myocardial ischemic risk with rosiglitazone. The 
      PROactive database provides an opportunity to investigate the effects of these 
      medications on the potential macrovascular benefits reported with pioglitazone. 
      METHODS: The PROactive study was a randomized double-blind prospective trial that 
      evaluated mortality and cardiovascular morbidity in 5238 patients with T2DM and 
      macrovascular disease. Patients received pioglitazone or placebo in addition to 
      their baseline glucose-lowering and cardiovascular medications. The effect of 
      pioglitazone on composite endpoints was evaluated, including all-cause death, 
      myocardial infarction (MI), and stroke, as well as safety events of edema and 
      serious heart failure, in subgroups using nitrates, RAS blockers, or insulin at 
      baseline. RESULTS: The risk of all-cause death, MI, and stroke for pioglitazone 
      versus placebo was similar regardless of the baseline use of nitrates, RAS 
      blockers, or insulin, with hazard ratios ranging from 0.81 to 0.87. Similar 
      results were obtained for the other composite endpoints analyzed. There were no 
      significant interactions between baseline medication subgroups and treatment. The 
      increased risk of edema and serious heart failure was consistent across the 
      baseline medication subgroups. CONCLUSIONS: This post hoc analysis did not reveal 
      an increased risk of macrovascular events with pioglitazone in patients receiving 
      nitrates, RAS blockers, or insulin. Rather, all patients realized the same trend 
      towards benefit with pioglitazone, and adverse events of edema and heart failure 
      were predictable.
CI  - (c) 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and 
      Blackwell Publishing Asia Pty Ltd.
FAU - Erdmann, Erland
AU  - Erdmann E
AD  - Medizinische Klinik III der Universitat zu Koln, Koln, Germany. 
      erland.erdmann@uni-koeln.de
FAU - Spanheimer, Robert
AU  - Spanheimer R
FAU - Charbonnel, Bernard
AU  - Charbonnel B
CN  - PROactive Study Investigators
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Australia
TA  - J Diabetes
JT  - Journal of diabetes
JID - 101504326
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Nitrates)
RN  - 0 (Thiazolidinediones)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Age of Onset
MH  - Aged
MH  - Angiotensin-Converting Enzyme Inhibitors/adverse effects/therapeutic use
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy/mortality
MH  - Diabetic Angiopathies/drug therapy/*epidemiology/mortality
MH  - Edema/drug therapy/epidemiology
MH  - Female
MH  - Heart Failure/drug therapy/epidemiology
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/*therapeutic use
MH  - Insulin/adverse effects/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Multicenter Studies as Topic
MH  - Myocardial Ischemia/*chemically induced/epidemiology
MH  - Nitrates/adverse effects/therapeutic use
MH  - Pioglitazone
MH  - Thiazolidinediones/adverse effects/*therapeutic use
EDAT- 2010/10/07 06:00
MHDA- 2011/02/03 06:00
CRDT- 2010/10/07 06:00
PHST- 2010/10/07 06:00 [entrez]
PHST- 2010/10/07 06:00 [pubmed]
PHST- 2011/02/03 06:00 [medline]
AID - 10.1111/j.1753-0407.2010.00082.x [doi]
PST - ppublish
SO  - J Diabetes. 2010 Sep;2(3):212-20. doi: 10.1111/j.1753-0407.2010.00082.x.