A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair.
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.


CONCLUSIONS
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.
Hackmann
Amy E
AE
Department of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St. Louis, Mo.
Rubin
Brian G
BG
Sanchez
Luis A
LA
Geraghty
Patrick A
PA
Thompson
Robert W
RW
Curci
John A
JA
D000368:Aged; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D001027:Aortography / Q000379:methods; D015415:Biomarkers / Q000097:blood; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D004108:Dilatation, Pathologic; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D005548:Foreign-Body Migration / Q000201:enzymology / Q000209:etiology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D061965:Matrix Metalloproteinase Inhibitors; D011475:Prosthesis Failure; D011480:Protease Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D015415:Biomarkers; D018836:Inflammation Mediators; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline