A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair.
A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair.
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DOI：
10.1016/j.jvs.2008.03.064
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发表时间：
2008-09
影响因子：
4.3
通讯作者：
Curci, John A.
中科院分区：
文献类型：
--
作者：
Hackmann, Amy E.;Rubin, Brian G.;Sanchez, Luis A.;Geraghty, Patrick A.;Thompson, Robert W.;Curci, John A.
血管内动脉瘤修复术(EVAR)的晚期持久性一直受到进行性主动脉退变的限制，这种退行性病变被认为是由基质金属蛋白(MMPs)介导的。本研究的目的是评估基质金属蛋白酶抑制剂多西环素对EVAR的影响。接受EVAR的患者被随机分为多西环素(每天两次，100毫克)或安慰剂，为期6个月。分别于术前、术后(仅采血)、术后1个月和6个月进行临床资料、血样和CT扫描。对44名受试者进行了意向治疗分析。6个月时，多西环素治疗组(N=20)患者血浆基质金属蛋白酶-9显著低于基线水平(−16.4±20.7%，P<；0.05)，而安慰剂组(N=24)则无显著升高(128.1±73.5%)。这主要与一到六个月之间的变化有关。在6个月发生内漏的患者中，安慰剂组有83%的患者血浆基质金属蛋白酶-9升高，而多西环素组只有14%(P<；.03)。在接受AneuRx或排除器内移植物的无内渗漏患者中，多西环素治疗导致的最大主动脉内径比安慰剂治疗组更大(−13.3±3.3%对−3.8±3.0%，P<；0.05)。此外，在排除治疗的患者中，多西环素治疗显著减少了6个月后的主动脉颈扩张。有证据表明内皮移植后持续释放的基质金属蛋白酶代表了正在进行的主动脉退化，这种退化可以被多西环素治疗所抑制。在基于所使用的血管内移植物的分析中，多西环素的治疗也证明了主动脉内径稳定性的增加，这是EVAR长期成功的替代标记物。虽然令人鼓舞，但这些结果需要在更大的患者群体中得到证实。作为一种潜在的辅助治疗，多西环素应该进行更彻底的评估，以改善EVAR的结果，特别是在某些亚组中。
The late durability of endovascular aneurysm repair (EVAR) has been limited by progressive aortic degeneration believed to be mediated by matrix metalloproteases (MMP). The goal of this study was to evaluate the effect of a MMP inhibitor, doxycycline, on EVAR. Patients undergoing EVAR were randomized to doxycycline (100mg twice daily) or placebo for 6 months following the procedure. Clinical data, blood samples and CT scans were obtained pre-operatively, post-operatively (blood only), and at 1 and 6 month follow-up. Forty-four subjects were analyzed based on intention-to-treat. Plasma MMP-9 decreased significantly below baseline in the doxycycline (N=20) treated patients at 6 months (−16.4±20.7%, P<0.05) while there was a non-significant increase in the placebo (N=24) group (128.1±73.5%). This was primarily related to changes between one and six months. In patients with endoleaks at 6 months, plasma MMP-9 increased in 83% of the placebo treated patients, but in only 14% of the doxycycline treated group (P<.03). Among endoleak-free patients with AneuRx or Excluder endografts, doxycycline treatment resulted in greater decreases in maximum aortic diameter than placebo treatment (−13.3±3.3% vs. −3.8±3.0%, P<.05). Furthermore, doxycycline treatment significantly reduced the aortic neck dilatation at six months in Excluder treated patients. There is evidence of persistent MMP release representing ongoing aortic degradation after endografting which can be inhibited by doxycycline therapy. In analyses based on the endograft used, treatment with doxycycline also demonstrated evidence of increased aortic dimensional stability, a surrogate marker for long-term success of EVAR. Although encouraging, these results require confirmation in larger patient populations. Doxycycline should undergo more thorough evaluation as a potential adjuvant treatment to improve the results of EVAR, particularly in certain subgroups.
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影响因子：
4.3
作者：
Matsumura, JS;Chaikof, EL
通讯作者：
Chaikof, EL
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4.3
作者：
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Sampran, ESK
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4.3
作者：
Tonnessen, BH;Sternbergh, WC;Money, SR
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Money, SR
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4.3
作者：
Curci, JA;Mao, DL;Thompson, RW
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Thompson, RW
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4.3
作者：
Hobo, R;Buth, J
通讯作者：
Buth, J