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中华临床医师杂志(电子版) ›› 2023, Vol. 17 ›› Issue (12) : 1277 -1284. doi: 10.3877/cma.j.issn.1674-0785.2023.12.011

临床药学

腹主动脉瘤的药物治疗进展:一项系统综述和网状荟萃分析
李瑞华, 周炜, 刘洋()   
  1. 250012 济南,山东大学齐鲁医院普外科血管外科
    250012 济南,山东大学齐鲁医院超声科
  • 收稿日期:2023-09-27 出版日期:2023-12-15
  • 通信作者: 刘洋
  • 基金资助:
    国家自然科学基金青年基金(82000451)

Pharmacological treatment of abdominal aortic aneurysm: a systematic review and network Meta-analysis

Ruihua Li, Wei Zhou, Yang Liu()   

  1. Department of General Surgery, Vascular Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
    Department of Ultrasound, Qilu Hospital of Shandong University, Jinan 250012, China
  • Received:2023-09-27 Published:2023-12-15
  • Corresponding author: Yang Liu
引用本文:

李瑞华, 周炜, 刘洋. 腹主动脉瘤的药物治疗进展:一项系统综述和网状荟萃分析[J]. 中华临床医师杂志(电子版), 2023, 17(12): 1277-1284.

Ruihua Li, Wei Zhou, Yang Liu. Pharmacological treatment of abdominal aortic aneurysm: a systematic review and network Meta-analysis[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(12): 1277-1284.

目的

利用网状荟萃分析寻找可以预防腹主动脉瘤扩张和破裂的药物,并对最新的研究进展进行综述。

方法

检索PubMed、Embase、Web of Science和Cochrane数据库,纳入截至2023年6月30日的针对腹主动脉瘤患者的药物治疗的随机对照试验,主要结局为腹主动脉瘤相关事件,即动脉瘤扩张或破裂。使用累积排序(SUCRA)曲线下的面积对干预药物进行排序,网状荟萃分析(NMA)在贝叶斯框架下进行,旨在探索可用于预防腹主动脉瘤扩张和破裂的药物。

结果

共纳入了10项随机对照研究,包括2 234例腹主动脉瘤患者。接受药物治疗的患者与接受安慰剂治疗的患者在腹主动脉瘤相关事件的发生率上无明显差异,汇总的相对危险度(RR)分别为:氨氯地平0.85 (95%CI: 0.28~2.58),阿奇霉素1.24 (95%CI: 0.51~3.07),多西环素0.98 (95%CI: 0.55~1.72),吡嘧司特2.39 (95%CI: 0.57~18.45),培哚普利1.21 (95%CI: 0.43~3.39),普萘洛尔1.22 (95%CI: 0.69~2.11),罗红霉素0.80(95%CI: 0.22~2.66),替米沙坦1.32 (95%CI: 0.47~3.83)。其中5项研究(共包括1 284例患者)报道了与药物治疗相关的不良事件,与安慰剂对比,多西环素、吡嘧司特和替米沙坦在不良事件的发生风险方面并无明显差异,汇总的RR值分别为1.06(95%CI:0.95~1.18)、1.01(95%CI:0.88~1.17)和1.07(95%CI:0.85~1.37)。

结论

网状荟萃分析结果表明,目前没有可有效治疗腹主动脉瘤的药物,仍需进一步的前瞻性随机对照试验研究。

Objective

To identify potential therapeutic agents for abdominal aortic aneurysm (AAA) patients by conducting a network Meta-analysis (NMA) and systematic review.

Methods

A literature search was conducted in PubMed, Embase, Web of Science, and Cochrane to identify randomized controlled trials (RCTs) on patients with AAA for further analysis. The primary outcome was AAA events, which were defined as AAA dilation or rupture. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the drugs. The Bayesian framework was used in an NMA to investigate drugs that could prevent dilatation and rupture of AAA.

Results

A total of 10 RCTs including 2234 patients with AAA were included. Patients under pharmacological therapies exhibited a comparable incidence of AAA events to those treated with placebo, with a pooled relative risk (RR) of 0.85 (95% confidence interval [CI]: 0.28-2.58), 1.24 (95%CI: 0.51-3.07), 0.98 (95%CI: 0.55-1.72), 2.39 (95%CI: 0.57-18.45), 1.21 (95%CI: 0.43-3.39), 1.22 (95%CI: 0.69-2.11), 0.80 (95%CI: 0.22-2.66), and 1.32 (95%CI: 0.47-3.83) for amlodipine, azithromycin, doxycycline, pemirolast, perindopril, propranolol, roxithromycin, and telmisartan, respectively. A total of 5 studies (1284 patients) reported adverse events associated with drug therapy. There was no significant difference in the risk of adverse events with doxycycline, pimirolast, and telmisartan compared with placebo, and the pooled RR values were 1.06 (95%CI: 0.95-1.18), 1.01 (95%CI: 0.88-1.17), and 1.07 (95%CI: 0.85-1.37), respectively.

Conclusion

This NMA demonstrated that no drugs have a definitive therapeutic effect on AAA, and further prospective RCTs are still required.

图1 本研究文献检索、纳入和排除的流程图
图2 本研究文献Cochrane偏倚风险评估工具结果
图3 腹主动脉瘤相关事件的漏斗图 注:A为安慰剂;B为多西环素;C为吡嘧司特;D为罗红霉素;E为普萘洛尔;F为替米沙坦;G为培哚普利;H为氨氯地平;I为阿奇霉素
表1 纳入网络荟萃分析的腹主动脉瘤药物治疗研究的基线特征
研究 地区 干预措施 例(男/女) 年龄(岁)a 腹主动脉瘤直径(mm)a 吸烟/不吸烟(例) 平均舒张压(mmHg)a 腹主动脉瘤事件(例) 所有预期不良事件(例)
Baxter[18] 美国 安慰剂 125(108/17) 70.9±7.3 44.0(40.0~47.0) 43/82 NR 9 111
多西环素 129(111/18) 71.0±7.5 43.0(40.0~46.0) 44/85 NR 13 121
Mosorin[19] 芬兰 安慰剂 15(13/2) 68.1 (64.1~73.0) 35.0(31.0~40.0) NR NR 3 NR
多西环素 17(16/1) 68.6 (64.4~71.3) 31.0(27.5~38.5) NR NR 2 NR
Meijer[20] 荷兰 安慰剂 142(114/28) 70.0±8.0 43.1±5.5 52/90 85.0±10.0 24 21
多西环素 144(120/24) 70.0±7.0 43.0±5.5 48/96 83.0±9.0 21 28
Vammen[21] 丹麦 安慰剂 49(NR) 73.0±3.7 36.9±5.1 29/20 85.5±12.8 7 NR
罗红霉素 43(NR) 72.0±3.7 38.1±5.7 26/17 86.5±13.1 5 NR
Karlsson[22] 加拿大 安慰剂 107(79/28) 71.0(67.0~76.0) 40.0(36.0~44.0) 40/65 NR 13 8
阿奇霉素 106(84/22) 71.0(67.0~74.0) 40.0(37.0~44.0) 40/66 NR 16 13
Sillesen[23] 欧洲 安慰剂 84(77/7) 70.7±5.7 44.0±2.8 34/50 NR 2 68
吡嘧司特 242(210/32) 70.8±6.3 44.2±2.8 96/146 NR 12 196
Lindholt[24] 丹麦 安慰剂 24(NR) 69.6±4.7 34.7±5.3 15/9 93.3±10.4 5 NR
普萘洛尔 30(NR) 68.7±6.4 34.6±5.6 21/9 98.0±10.6 7 NR
Investigators[25] 加拿大 安慰剂 282(233/49) 68.7(61.1~76.3) 39.0(34.0~45.0) NR 82.0(63.0~101.0) 58 NR
普萘洛尔 266(227/39) 69.1(61.0~77.2) 39.0(34.0~45.0) NR 83.0(73.0~93.0) 73 NR
Golledge[26] 澳大利亚 安慰剂 101(91/10) 73.8±7.8 43.1±5.2 27/74 78.0±9.0 8 58
替米沙坦 106(92/14) 73.2±8.1 43.3±5.8 23/83 80.0±10.0 11 65
Bicknell[27] 英国 安慰剂 79(74/5) 70.7±7.5 41.0±7.0 17/62 77.9±7.6 9 NR
培哚普利 73(71/2) 71.6±6.9 41.0±7.0 21/52 76.7±8.0 10 NR
氨氯地平 72(66/6) 71.5±6.7 40.0±7.0 18/54 78.0±7.0 7 NR
图4 8种药物关于腹主动脉瘤相关事件的比较的网络图。 注:不同的圆圈代表着不同的治疗药物,连线代表两个节点之间存在直接比较,连线的粗细表示直接比较的次数的多少,越多越粗
表2 药物治疗与腹主动脉瘤相关事件的网状荟萃分析结果 [RR(95%Cl)]
图5 腹主动脉瘤不同治疗药物的累积排序图与累积排序曲线下面积(SUCRA)X轴表示排名,Y轴表示累积概率,累积排序曲线下面积越大,药物治疗效果越好,8种药物和安慰剂的累积概率一致,其治疗效果无明显差异
图6 腹主动脉瘤不同治疗药物的排名概率图 在横轴上是九个可能的等级,在纵轴上是药物治疗效果达到每个等级的概率,8种药物和安慰剂可达到的治疗效果无明显差异
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