ARTA: AT1-receptor blocker therapy in patients undergoing coronary artery bypass grafting.
BACKGROUND
Decline in renal and cognitive function may complicate early recovery after coronary-artery bypass grafting. AT(1)-receptor antagonists have been demonstrated to be neuro- and renoprotective. Aim of ARTA, a prospective, double-blind, randomised and placebo controlled study, was to detect whether preoperative treatment with candesartan influences postoperative cognitive and renal function.


METHODS
One hundred and five patients eligible for coronary artery bypass graft surgery (65-85 years old, all suffering from hypertension and coronary artery disease, with stable kidney function) were randomized to candesartan (8 mg od) or placebo for between 8 and 11 days prior to surgery. Existing ACE-inhibitor/angiotensin receptor antagonist-therapy had to be stopped prior to the study. Validated cognitive function tests (trail making, Horn's perfomance III und VI, divided attention and change of reaction, memory - immediate and delayed recall, digit span) were performed preoperatively, 1 week and 3 months after surgery. Renal function was assessed by creatinine clearance on the day before, 1 week and 3 months after surgery.


RESULTS
Eighty-seven patients (n = 43 Candesartan, n = 44 placebo) were included in the ITT-population for analysis. Drug treatment had no adverse effect on perioperative blood pressure. Only five patients experienced a period of hypotension during introduction of anaesthesia (Candesartan 1/44, placebo 4/44). One week as well as three months after surgery, there were no differences in relevant cognitive function parameters compared to the status prior to surgery, independent from treatment. Creatinine clearance showed a clear decrease one week after surgery with a minor further reduction observed 3 months after surgery, but there was no difference between Candesartan and placebo treated patients. Between both groups, there were no significant differences in the number of adverse events and number of patients with adverse events nor in the incidence of renal failure with consecutive dialysis and cerebral strokes (candesartan 2, placebo 5) and possibly drug related severe adverse events.


CONCLUSIONS
This randomised placebo-controlled and prospective study in elderly patients does not support previous reports suggesting a substantial impairment of cognitive function after coronary artery bypass graft surgery. Preservation of cognitive and renal function was independent of pre-surgical administration of candesartan.
Flesch
Markus
M
Klinik III für Innere Medizin der, Universität zu Köln, Kerpener Strasse 62, 50937, Cologne, Germany. markus.flesch@uni-koeln.de
Knipp
Stephan
S
Kessler
Gerhard
G
Geissler
Hans-Joachim
HJ
Massoudy
Parwis
P
Wilhelm
Hans
H
Philipp
Thomas
T
Erdmann
Erland
E
D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D001026:Coronary Artery Bypass / Q000009:adverse effects; D003324:Coronary Artery Disease / Q000601:surgery; D003404:Creatinine / Q000097:blood / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control*; D011300:Preoperative Care; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000209:etiology / Q000517:prevention & control; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003404:Creatinine; C081643:candesartan