Flesch Markus, Knipp Stephan, Kessler Gerhard, Geissler Hans-Joachim, Massoudy Parwis, Wilhelm Hans, Philipp Thomas, Erdmann Erland
Klinik III für Innere Medizin der, Universität zu Köln, Kerpener Strasse 62, 50937, Cologne, Germany.
Clin Res Cardiol. 2009 Jan;98(1):33-43. doi: 10.1007/s00392-008-0719-9. Epub 2008 Oct 13.
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.
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.
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.
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.
冠状动脉搭桥术后早期恢复过程中，肾功能和认知功能下降可能会使情况变得复杂。已证实AT(1)受体拮抗剂具有神经保护和肾脏保护作用。ARTA是一项前瞻性、双盲、随机且安慰剂对照研究，其目的是检测术前使用坎地沙坦治疗是否会影响术后认知功能和肾功能。
105例符合冠状动脉搭桥手术条件的患者（年龄65 - 85岁，均患有高血压和冠状动脉疾病，肾功能稳定）在手术前8至11天被随机分为坎地沙坦组（每日8毫克）或安慰剂组。研究前必须停用现有的ACE抑制剂/血管紧张素受体拮抗剂治疗。术前、术后1周和3个月进行经过验证的认知功能测试（连线试验、霍恩操作III和VI、注意力分散和反应变化、记忆 - 即时和延迟回忆、数字广度）。在手术前一天、术后1周和3个月通过肌酐清除率评估肾功能。
87例患者（n = 4组坎地沙坦，n = 44组安慰剂）被纳入意向性分析人群。药物治疗对围手术期血压无不良影响。仅5例患者在麻醉诱导期间出现低血压期（坎地沙坦组1/44，安慰剂组4/44）。术后1周和3个月，与手术前状态相比，相关认知功能参数无差异，与治疗无关。肌酐清除率在术后1周明显下降，术后3个月进一步略有下降，但坎地沙坦组和安慰剂组患者之间无差异。两组之间，不良事件数量、发生不良事件的患者数量、连续性透析和脑卒中等肾衰竭发生率以及可能与药物相关的严重不良事件方面均无显著差异（坎地沙坦组2例，安慰剂组5例）。
这项针对老年患者的随机安慰剂对照前瞻性研究不支持先前关于冠状动脉搭桥手术后认知功能严重受损的报道。认知功能和肾功能的保留与术前给予坎地沙坦无关。
