CLINICAL RESEARCH: CLINICAL TRIAL
The Effect of Pioglitazone on Recurrent Myocardial Infarction in 2,445 Patients With Type 2 Diabetes and Previous Myocardial InfarctionResults From the PROactive (PROactive 05) Study
Erland Erdmann, MD, FESC, FACC*,1,*,
John A. Dormandy, FRCS, DSc ,1,
Bernard Charbonnel, MD ,1,
Massimo Massi-Benedetti, MD ,1,
Ian K. Moules, BSc (Hons)||,2,
Allan M. Skene, PhD¶,3 on behalf of the PROactive Investigators
* Medizinische Klinik III der Universität zu Köln, Köln, Germany
St. George’s Hospital, London, United Kingdom
Clinique d’Endocrinologie, Hôtel Dieu, Nantes, France
University of Perugia, Medicine and Metabolic Diseases, Perugia, Italy
|| Takeda Global Research and Development Centre (Europe) Ltd., London, United Kingdom
¶ Nottingham Clinical Research Ltd., Nottingham, United Kingdom.
Manuscript received August 25, 2006;
revised manuscript received November 2, 2006,
accepted December 4, 2006.
* Reprint requests and correspondence: Prof. Dr. Erland Erdmann, Medizinische Klinik III der Universität zu Köln, Kerpener Str. 62, D-50937 Köln, Germany. (Email: erland.erdmann{at}uni-koeln.de).
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
[ClinicalTrials.gov]
).
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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 |
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