The main results of PROactive were presented at the plenary session of the 41st Annual Meeting of the European Association for the Study for Diabetes (EASD) on 12th September 2005.

We showed that there was a non-significant 10% risk reduction in the primary end point of all-cause mortality, non-fatal MI (including silent MI), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries and amputation above the ankle with pioglitazone relative to placebo (HR 0.90, 95% CI 0.80–1.02, p=0.095). There was a significant 16% risk reduction in the main secondary end point of all-cause mortality, non-fatal MI and stroke with pioglitazone relative to placebo (HR 0.84, 95% CI 0.72–0.98, p=0.027). These key data were published in the Lancet 2005. A copy of the paper can be downloaded by clicking here.

The webcast of the EASD plenary presentations can be viewed in its entirety or by speaker. Please click on the relevant link on the right. The full PowerPoint presentation can be viewed or downloaded in English, German, Italian or Spanish. Please click the link on the right.

At the World Congress of Cardiology (WCC) in Barcelona on 3rd September 2006, Professor Robert Wilcox presented a prespecified subgroup analysis of the 984 patients who all had previous stroke. We showed that pioglitazone significantly reduced the risk of recurrent stroke by 47% relative to placebo in this high-risk population with type 2 diabetes and previous stroke. The PowerPoint presentation can be viewed by clicking the link on the right. These data have been published in Stroke. Please click here to download the publication.

Major Adverse Cardiovascular Events (MACE)

At the American Diabetes Association (ADA) in Washington on 12th June 2006, Dr Stuart Kupfer presented a subgroup analysis of the prespecified MACE end point of cardiovascular death, non-fatal MI, or non-fatal stroke (MACE1) and on six post-hoc MACE composites (various combinations of: all-cause, cardiovascular, or cardiac mortality, plus non-fatal MI, plus non-fatal stroke, and/or acute coronary syndrome in patients with type 2 diabetes. It was shown that that pioglitazone treatment resulted in significant risk reductions in these MACE composite end points to 3 years. The PowerPoint presentation can be viewed by clicking the link on the right. These data have been published in American Heart Journal.

Heart Failure

In 2007, an analysis of the heart failure cases in PROactive was published in Diabetes Care. This analysis was performed to assess the effects of treatment on morbidity and mortality following reports of serious heart failure. Although the incidence of serious heart failure was increased with pioglitazone compared with placebo in the total PROactive population of patients with type 2 diabetes and macrovascular disease, subsequent mortality or morbidity was not increased in pioglitazone-treated patients who had a serious heart failure event during the study. The associated PowerPoint presentation can be viewed by clicking the link on the right.

Chronic Kidney Disease

Most recently, we published results from a post-hoc analysis of an important subgroup of 597 patients with chronic kidney disease in the Journal of the American Society of Nephrology.  This is the first report of the effects of drug intervention on secondary cardiovascular prevention in patients with chronic kidney disease, type 2 diabetes and macrovascular disease. We tested two hypotheses: (1) that GFR is a strong independent prognostic marker in high cardiovascular risk patients with diabetes and (2) that pioglitazone is most effective in patients with moderate to severe renal insufficiency (GFR < 60 ml/min/1.73 m²). The data confirmed that chronic kidney disease (as measured by GFR < 60 ml/min/1.73 m²) is an independent risk factor for major adverse cardiovascular events and death, even amongst a very high-risk population of patients with diabetes and pre-existing macrovascular disease. In these patients with moderate to severe renal disease (GFR < 60 ml/min/1.73 m²), pioglitazone reduced all-cause death, MI and stroke independently of renal function. The associated PowerPoint presentation can be viewed by clicking the link on the right.