PERindopril-Function of the Endothelium in Coronary Artery Disease Trial: the PERFECT study--sub study of EUROPA: rationale and design.

BACKGROUND

ACE inhibition reduces morbidity and mortality among a variety of patients. Among mechanisms explaining these beneficial effects are the effects on the sympathetic system and on local vasodilating substances such as nitric oxide and bradykinins at the level of the endothelium. The PERFECT study was designed to verify the above mentioned pathophysiological concepts.

METHODS

The PERFECT study is a study nested within the EUROPA trial, a three year double-blind, multi-centre, placebo-controlled randomised study that aims at studying the effect of the ACE-inhibitor Perindopril on morbidity and mortality in over 12,000 patients with stable coronary artery disease without clinical heart failure. The PERFECT study is designed as a parallel group randomised placebo controlled trial to determine the effect of Perindopril (8 mg) on brachial artery endothelial function in patients with stable coronary artery disease without clinical heart failure. In the PERFECT study, B-mode ultrasonography of the brachial artery is used as a model for changes in the coronary arteries. Endothelial function in response to ischaemia (reactive hyperaemia) and to vasoconstriction (cold pressor test) is assessed. The ischemia test is used a model to assess the effects of ACE inhibition on nitric oxide/bradykinine mediated vasodilatatory response to ischaemia, whereas the cold pressor test is applied to assess the effect of ACE inhibition on the neurohormonal response. The recruitment for the PERFECT study started in May 1998 en was completed in June 1999. 345 patients were recruited in 20 European centers. The Vascular Imaging Center Utrecht, an ultrasound core laboratory, is performing the endothelial function measurements. The primary study outcomes are (1) percentage change in flow-mediated vasodilatation of the brachial artery between the 36 month measurement and the baseline measurement and (2) percentage change in neurohormonal mediated vasoconstriction of the brachial artery between the 36 month measurement and the baseline measurement. The size of the study allows detection of an absolute difference in FMD of 2.0% with a 90% power and a two-sided alpha of 5%.

CONCLUSION

The findings of the PERFECT study may help to understand and explain the effects of ACE inhibition, in particular Perindopril, on cardiovascular morbidity and mortality.