Clinical Research
Clinical Trial
The Effect of Pioglitazone on Recurrent Myocardial Infarction in 2,445 Patients With Type 2 Diabetes and Previous Myocardial Infarction: Results From the PROactive (PROactive 05) Study

https://doi.org/10.1016/j.jacc.2006.12.048Get rights and content
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Objectives

This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI).

Background

People with type 2 diabetes have an increased incidence of MI compared with the general population. Those with diabetes and MI have a worse prognosis than nondiabetic patients with cardiovascular disease.

Methods

The PROactive study was a prospective, multicenter, double-blind, placebo-controlled trial of 5,238 patients with type 2 diabetes and macrovascular disease. Patients were randomized to either pioglitazone or placebo in addition to their other glucose-lowering and cardiovascular medication. Treatment of diabetes, dyslipidemia, and hypertension was encouraged according to the International Diabetes Federation guidelines. Patients were followed for a mean of 2.85 years. The primary end point was the time to first occurrence of macrovascular events or death. Of the total cohort, the subgroup of patients who had a previous MI (n = 2,445 [46.7%]; n = 1,230 in the pioglitazone group and n = 1,215 in the placebo group) was evaluated using prespecified and post-hoc analyses.

Results

Pioglitazone had a statistically significant beneficial effect on the prespecified end point of fatal and nonfatal MI (28% risk reduction [RR]; p = 0.045) and acute coronary syndrome (ACS) (37% RR; p = 0.035). There was a 19% RR in the cardiac composite end point of nonfatal MI (excluding silent MI), coronary revascularization, ACS, and cardiac death (p = 0.033). The difference in the primary end point defined in the main PROactive study did not reach significance in the MI population (12% RR; p = 0.135). The rates of heart failure requiring hospitalization were 7.5% (92 of 1,230) with pioglitazone and 5.2% (63 of 1,215) with placebo. Fatal heart failure rates were similar (1.4% [17 of the 92] with pioglitazone versus 0.9% [11 of the 63] with placebo).

Conclusions

In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS. (PROspective pioglitAzone Clinical Trial In macroVascular Events; http://www.clinicaltrials.gov/ct/show/NCT00174993?order = 1; ISRCTN NCT00174993).

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
ACS
acute coronary syndrome
CABG
coronary artery bypass graft
ECG
electrocardiogram
HDL
high-density lipoprotein
HF
heart failure
IDF
International Diabetes Federation
LDL
low-density lipoprotein
MI
myocardial infarction
PCI
percutaneous coronary intervention

Cited by (0)

This study was funded by Takeda Europe R&D Centre Ltd., London, United Kingdom, and Eli Lilly and Company, Indianapolis, Indiana.

1

Drs. Erdmann, Dormandy, Charbonnel, and Massi-Benedetti have served as consultants to, and/or received travel expenses and payments for speaking at meetings from, Takeda.

2

Mr. Moules is an employee of Takeda Pharmaceuticals.

3

Dr. Skene is the managing director of Nottingham Clinical Research Limited, which was contracted by Takeda.