Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial.
BACKGROUND
Doxycycline inhibits formation and progression of abdominal aortic aneurysms (AAAs) in preclinical models of the disease, but it is unclear whether and how this observation translates to humans.


OBJECTIVE
To test whether doxycycline inhibits AAA progression in humans.


METHODS
Randomized, placebo-controlled, double-blind trial. (Dutch Trial Registry: NTR 1345) SETTING: 14 Dutch hospitals.


METHODS
286 patients with small AAAs between October 2008 and June 2011.


METHODS
Daily dose of 100 mg of doxycycline (n = 144) or placebo (n = 142) for 18 months.


METHODS
The primary outcome measure was aneurysm growth at 18 months, as estimated by repeated single-observer ultrasonography. Secondary outcomes included growth at 6 and 12 months and the need for elective surgery.


RESULTS
Mean aneurysm diameter (approximately 43 mm) and other baseline characteristics were similar in both groups. Doxycycline treatment was associated with increased aneurysm growth (4.1 mm in the doxycycline group vs. 3.3 mm in the placebo group at 18 months; difference, 0.8 mm [95% CI, 0.1 to 1.4 mm]; P = 0.016 mm). Twenty-one patients receiving doxycycline and 22 patients receiving placebo had elective surgical repair (Kaplan–Meier estimates were 16.1% for those receiving doxycycline and 16.5% for those receiving placebo; difference, -0.4% [CI, -9.3% to 8.5%]; P = 0.83). Time to repair was similar in the groups (P = 0.92).


CONCLUSIONS
This study focuses on patients with small AAAs. As such, whether the data can be extrapolated to larger AAAs (>55 mm) is unclear. The high number of elective repairs (n = 43) was unanticipated. Moreover, the study did not follow patients who withdrew because of an adverse effect.


CONCLUSIONS
This trial found that 18 months of doxycycline therapy did not reduce aneurysm growth and did not influence the need for AAA repair or time to repair.


BACKGROUND
The Netherlands Organisation for Health Research and Development, and the NutsOhra Fund.
C Arnoud
CA
Meijer
Theo
T
Stijnen
Martin N J M
MN
Wasser
Jaap F
JF
Hamming
J Hajo
JH
van Bockel
Jan H N
JH
Lindeman
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D001019:Aortic Rupture / Q000601:surgery; D018450:Disease Progression; D004311:Double-Blind Method; D004318:Doxycycline / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D014463:Ultrasonography
D000893:Anti-Inflammatory Agents; D061965:Matrix Metalloproteinase Inhibitors; D004318:Doxycycline