Data from the PROactive Study, presented at the 41st meeting of the European Association for the Study of Diabetes ( EASD ) in Athens, demonstrated that Actos ( Pioglitazone ) significantly reduces the combined risk of heart attacks, strokes and death by 16% in high risk patients with type 2 diabetes.

" The PROactive study is the first in the world to prospectively show that a specific oral glucose lowering medication, namely Pioglitazone, can significantly improve cardiovascular outcomes by helping to delay or reduce heart attacks, strokes and death in high-risk patients,” said John Dormandy, at St. George's Hospital, London, UK, and chairman of the PROactive Study Steering Committee. "

PROactive ( PROspective PioglitAzone Clinical Trial In MacroVascular Events ) was a randomised, double blind, placebo-controlled outcome study to determine the effects of Pioglitazone on mortality and morbidity associated with cardiovascular disease progression in more than 5,000 high risk patients with type 2 diabetes when added to standard of care treatment.
Standard of care included the routine use of anti-hypertensives such as ACE inhibitors and beta blockers; glucose lowering agents such as Metformin, sulphonylureas and Insulin; antiplatelet drugs such as Aspirin, and lipid-modifying medicines such as statins and fibrates.

This PROactive study focused on two key endpoints: a primary combination endpoint of seven different macrovascular events of varying clinical importance; and a principal secondary combination endpoint of life-threatening events including death, heart attack and stroke.

The primary endpoint was reduced by 10% but had not reached statistical significance by study end ( p=0.095 ).
The principal secondary endpoint of life-threatening events showed that Pioglitazone significantly reduced the risk of heart attacks, strokes and death by 16% ( p=0.027 ).

According to Dormandy, these results predict that 10 heart attacks, strokes or deaths will be prevented for every 500 high-risk patients treated with Actos over three years.

Additional PROactive study results of Actos showed:

- HbA1c levels ( a measurement of long-term blood glucose control ) were significantly reduced as compared to placebo ( p<0.001 ).

- Lipid profiles significantly improved by increasing HDL cholesterol by 9% more than placebo ( p<0.001 ), and reducing triglycerides by 13% more than placebo ( p<0.001 ).

- The LDL/HDL cholesterol ratio was significantly improved ( p<0.001 ). A 2% increase in LDL cholesterol was observed compared to placebo ( p=0.003 ).

- Systolic blood pressure was significantly decreased ( p=0.03 ); median change of 3 mmHg more than produced by placebo.

The PROactive Study was also designed to further examine the safety of Pioglitazone in this high-risk patient group.
The results demonstrated that adverse events reported in this study were consistent with the established safety profile. Glycaemia and heart failure were observed more frequently compared to placebo.
There were no reports of acute liver toxicity.

Source: Takeda, 2005


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