ACE inhibition and endothelial function: main findings of PERFECT, a sub-study of the EUROPA trial.
BACKGROUND
ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction.


METHODS
PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months.


RESULTS
In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval -0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07).


CONCLUSIONS
Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD.
Julius Center for Health Sciences and Primary Care, HP Str 6.131, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. m.l.bots@umcutrecht.nl
M L
ML
Bots
W J
WJ
Remme
T F
TF
Lüscher
K M
KM
Fox
M
M
Bertrand
R
R
Ferrari
M L
ML
Simoons
D E
DE
Grobbee
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D020913:Perindopril / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril