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A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair
Amy E Hackmann1, Brian G Rubin, Luis A Sanchez
1Department of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St. Louis, Mo.
Background:
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.
Methods:
Patients undergoing EVAR were randomized to doxycycline (100 mg twice daily) or placebo for 6 months following the procedure. Clinical data, blood samples, and computed tomography (CT) scans were obtained preoperatively, postoperatively (blood only), and at 1- and 6-month follow-up. Forty-four subjects were analyzed based on intention-to-treat.
Results:
Plasma MMP-9 decreased significantly below baseline in the doxycycline (N = 20) treated patients at 6 months (-16.4% +/- 20.7%, P < .05) while there was a nonsignificant increase in the placebo (N = 24) group (128.1% +/- 73.5%). This was primarily related to changes between 1 and 6 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 6 months in Excluder treated patients.
Conclusion:
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.
Insights
Doxycycline therapy inhibited matrix metalloproteinase-9 (MMP-9) levels after endovascular aneurysm repair (EVAR), improving aortic dimensional stability. This suggests doxycycline may enhance long-term EVAR success, particularly in specific patient subgroups.
Area of Science:
- Cardiovascular Surgery
- Endovascular Interventions
- Pharmacological Adjuncts
Background:
- Endovascular aneurysm repair (EVAR) durability is limited by progressive aortic degeneration.
- Matrix metalloproteinases (MMPs) are implicated in this post-EVAR aortic degradation.
- Investigating MMP inhibitors like doxycycline is crucial for improving EVAR outcomes.
Purpose of the Study:
- To evaluate the efficacy of doxycycline, an MMP inhibitor, in mitigating aortic degeneration after EVAR.
- To assess the impact of doxycycline on plasma MMP-9 levels and aortic dimensions post-EVAR.
Main Methods:
- Randomized controlled trial comparing doxycycline (100 mg twice daily) versus placebo for 6 months post-EVAR.
- Collection of clinical data, blood samples for MMP-9 analysis, and CT scans for aortic measurements.
- Intention-to-treat analysis of 44 subjects with pre-operative, post-operative, and 1- and 6-month follow-up.
Main Results:
- Doxycycline significantly reduced plasma MMP-9 levels at 6 months compared to placebo.
- Doxycycline mitigated MMP-9 increases in patients with endoleaks.
- Doxycycline treatment led to greater reduction in maximum aortic diameter and aortic neck dilatation in specific endograft types.
Conclusions:
- Doxycycline therapy effectively inhibits MMP release and promotes aortic dimensional stability after EVAR.
- These findings suggest doxycycline as a potential adjuvant treatment to improve long-term EVAR success.
- Larger studies are warranted to confirm these encouraging results and explore specific patient subgroups.
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