Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial
CA Meijer, T Stijnen, MNJM Wasser… - Annals of internal …, 2013 - acpjournals.org
CA Meijer, T Stijnen, MNJM Wasser, JF Hamming, JH van Bockel, JHN Lindeman
Annals of internal medicine, 2013•acpjournals.orgBackground: 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 …
(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 …
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.
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