CHICAGO -- Type 2 diabetes patients with chronic kidney disease may get at least some moderate cardiovascular risk reduction from pioglitazone (Actos), researchers found.
CHICAGO, June 25 -- Type 2 diabetes patients with chronic kidney disease may get at least somee moderate cardiovascular risk reduction from pioglitazone (Actos, researchers found.
Compared with placebo in a large trial, diabetic chronic kidney disease patients given pioglitazone had 6.8% less all-cause mortality, myocardial infarction, or stroke events, versus a nonsignificant 1.3% reduction for those without chronic kidney disease, reported Erland Erdmann, M.D., and Christian A. Schneider, M.D., both of the University of Cologne in Germany, and colleagues.
Their subanalyses of the PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) study were presented at the American Diabetes Association meeting here. The primary analysis of the PROactive study was negative, as reported in 2005 at the European Association for the Study of Diabetes meeting and in The Lancet.
The composite primary endpoint included all-cause mortality, non-fatal myocardial infarction, acute coronary syndrome, stroke, coronary or carotid artery intervention, leg revascularization, and foot amputation. It was not significantly different between pioglitazone and placebo (P=0.095).
To explore benefits for subpopulations, the researchers looked at the 597 type 2 diabetes patients with chronic kidney disease (defined as glomerular filtration rate less than 60 mL/min/1.73 m2) compared with the 4,557 without kidney dysfunction.
All had been randomized to 10 to 15 mg/day of pioglitazone or placebo on top of their existing glucose-lowering and cardiovascular medications. They also were required to have a history of cardiovascular disease.
The patients with kidney disease were older, had a longer duration of diabetes, and were more likely to have hypertension than those without kidney dysfunction.
Unsurprisingly, the kidney disease patients had a higher primary composite endpoint rate (27.5% versus 19.6%, hazard ratio 1.51, 95% confidence interval 1.28 to 1.78, P
Primary endpoint occurrence rates were 7.0% lower among chronic kidney disease patients on pioglitazone versus placebo but the difference was not statistically significant (23.7% versus 30.7%, P=NS). The reduction was only 1.2% among patients without chronic kidney disease with pioglitazone versus placebo and was also not significant (19.0% versus 20.2%, P=NS).
Secondary endpoint occurrence rates for pioglitazone versus placebo were 6.8% lower among chronic kidney disease patients on pioglitazone versus placebo (14.6% versus 21.4%, hazard ratio=0.66; 95%CI=0.45-0.98). Among patients without chronic kidney disease, the difference was only 1.3% and was not significant (10.9% versus 12.2%, hazard ratio=0.89; 95%CI=0.75-1.05P=NS).
The effect of pioglitazone compared with placebo was similar regardless of patients' glomerular filtration rates. The interaction between kidney function and cardiovascular event rates was not significant for either the primary endpoint (P=0.1923) or the secondary endpoint (P=0.1781).