Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial

Abstract

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.

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

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

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

Measurements: 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).

Limitations: 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.

Conclusion: 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.

Primary funding source: The Netherlands Organisation for Health Research and Development, and the NutsOhra Fund.