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).

Abstract

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.

• Authors: Erland Erdmann, Robert Spanheimer, Bernard Charbonnel, PROactive Study Investigators
• Journal: Journal of diabetes (J Diabetes) Vol. 2 Issue 3 Pg. 212-20 (Sep 2010) ISSN: 1753-0407 [Electronic] Australia
• PMID: 20923486 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Hypoglycemic Agents
• Insulin
• Nitrates
• Thiazolidinediones
• Pioglitazone

Topics

• Age of Onset
• Aged
• Angiotensin-Converting Enzyme Inhibitors (adverse effects, therapeutic use)
• Diabetes Mellitus, Type 2 (complications, drug therapy, mortality)
• Diabetic Angiopathies (drug therapy, epidemiology, mortality)
• Edema (drug therapy, epidemiology)
• Female
• Heart Failure (drug therapy, epidemiology)
• Humans
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Insulin (adverse effects, therapeutic use)
• Male
• Middle Aged
• Multicenter Studies as Topic
• Myocardial Ischemia (chemically induced, epidemiology)
• Nitrates (adverse effects, therapeutic use)
• Pioglitazone
• Thiazolidinediones (adverse effects, therapeutic use)