Cited 101 times since 2013 (9.7 per year) source: EuropePMC Annals of internal medicine, Volume 159, Issue 12, 1 1 2013, Pages 815-823 Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial. Meijer CA, Stijnen T, Wasser MN, Hamming JF, van Bockel JH, Lindeman JH, Pharmaceutical Aneurysm Stabilisation Trial Study Group

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.

Ann Intern Med. 2013 12;159(12):815-823