A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair
Received 19 December 2007; accepted 31 March 2008. published online 16 July 2008.
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.
aDepartment of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St. Louis, Mo
bDepartment of Radiology, Washington University School of Medicine, St. Louis, Mo
cCell Biology and Physiology, Washington University School of Medicine, St. Louis, Mo
Correspondence: John A. Curci, MD, Department of Surgery, Section of Vascular Surgery, Washington University in Saint Louis, 660 S Euclid Ave, Campus Box 8109, Saint Louis, MO 63110
Supported by grants from the Barnes-Jewish Hospital Foundation (J.A.C.), National Institutes for Health (5K08HL084004-02, J.A.C.), Department of Veteran's Affairs (J.A.C.), Flight Attendants Medical Research Institute (J.A.C.), and the American Heart Association (0765432Z, J.A.C.).
Competition of interest: Dr Geraghty has received consulting fees from W. L. Gore and Associates. Dr Sanchez has received consulting fees from W. L. Gore and Associates, Cook, and Medtronic.
ABSTRACT