Institute of Clinical Pharmacology, Medical Faculty of the University of Technology, Dresden, Germany.
Clin Drug Investig. 2005;25(2):89-97. doi: 10.2165/00044011-200525020-00001.
In this prospective, double-blind, placebo-controlled study we observed the influence of treatment with candesartan 8mg on restenosis rates after stent implantation into the femoral artery 6 months after percutaneous transluminal angioplasty (PTA). We hypothesised that angiotensin II type 1 (AT1)-receptor blockade with candesartan would reduce restenosis rates by reducing angiotensin II-mediated intima hyperproliferation within the stented vessel segment in patients with peripheral occlusive disease.
Eighty-seven patients with peripheral occlusive arterial disease stage IIb who had been successfully treated with PTA and stent implantation were randomised to receive orally either candesartan 8mg (n = 44) or placebo (n = 43). Follow-up included evaluation of the degree of stenosis and thickness of the intima-media complex (primary endpoint). In addition, thickness of the interventricular septum, crurobrachial pressure ratios, and pain-free walking distance were determined (secondary endpoints).
The degree of stenosis after 6 months was not significantly different between the groups studied (35.9 +/- 39.6% for candesartan vs 36.0 +/- 38.4% for placebo). Relevant restenosis including stent occlusions was found in nine patients (20.5%) in the candesartan group and in ten patients (23.3%) in the placebo group. The thickness of the intima-media complex 6 months after stent implantation was 1.60 +/- 0.32mm in the candesartan group and 1.64 +/- 0.32mm in the placebo group (not significant). There were no differences in secondary endpoints between the treatment groups. Controls after 3 months (20.9 +/- 33.6% for candesartan vs 27.6 +/- 38.3% for placebo; p = 0.39) and 9 months (44.1 +/- 40.8% for candesartan vs 47.7 +/- 37.2% for placebo; p = 0.67) of therapy revealed a lower degree of stenosis in patients treated with candesartan.
Although not significant, candesartan treatment tended to improve the prognostic benefits after stent implantation, suggesting that an antiproliferative effect after stenting may need higher doses than an antihypertensive effect of the drug. This hypothesis requires confirmation in further prospective studies with higher daily doses of candesartan, which are already in progress.
在这项前瞻性、双盲、安慰剂对照的研究中，我们观察了血管紧张素Ⅱ 1 型（AT1）受体拮抗剂坎地沙坦治疗对经皮腔内血管成形术后 6 个月股动脉支架植入后再狭窄率的影响。我们假设，坎地沙坦通过减少支架血管段内血管紧张素Ⅱ介导的内膜过度增殖，可降低外周闭塞性疾病患者的再狭窄率。
87 例外周闭塞性动脉疾病Ⅱ b 期患者成功接受经皮腔内血管成形术和支架植入术治疗，随机口服坎地沙坦 8mg（n = 44）或安慰剂（n = 43）。随访包括评估狭窄程度和内膜中层复合体厚度（主要终点）。此外，还测定了室间隔厚度、肱股压力比和无痛步行距离（次要终点）。
6 个月后两组的狭窄程度无显著差异（坎地沙坦组为 35.9 ± 39.6%，安慰剂组为 36.0 ± 38.4%）。坎地沙坦组 9 例（20.5%）和安慰剂组 10 例（23.3%）出现相关再狭窄，包括支架闭塞。支架植入后 6 个月内膜中层复合体厚度为坎地沙坦组 1.60 ± 0.32mm，安慰剂组 1.64 ± 0.32mm（无显著性差异）。两组间次要终点无差异。治疗 3 个月（坎地沙坦组 20.9 ± 33.6%，安慰剂组 27.6 ± 38.3%；p = 0.39）和 9 个月（坎地沙坦组 44.1 ± 40.8%，安慰剂组 47.7 ± 37.2%；p = 0.67）的对照组显示，坎地沙坦治疗组狭窄程度较低。
尽管无统计学意义，但坎地沙坦治疗倾向于改善支架植入后的预后获益，提示支架置入后的抗增殖作用可能需要比药物的降压作用更高的剂量。这一假设需要在正在进行的更高剂量坎地沙坦的前瞻性研究中进一步证实。
