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Randomized Controlled Trial
. 2024 Jul:104:1-9.
doi: 10.1016/j.avsg.2023.06.019. Epub 2023 Jun 24.

Effect of Doxycycline on Progression of Arterial Calcification in the Noninvasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT)

Tanner I Kim  1 , Valentyna Kostiuk  2 , Sydney L Olson  3 , John A Curci  4 , Jon S Matsumura  5 , Bernard T Baxter  6 , William C Blackwelder  7 , Michael L Terrin  7 , Raul J Guzman  8
Affiliations
Randomized Controlled Trial

Effect of Doxycycline on Progression of Arterial Calcification in the Noninvasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT)

Tanner I Kim et al. Ann Vasc Surg. 2024 Jul.

Abstract

Background: Doxycycline has been shown to prevent arterial calcification via attenuation of matrix metalloproteinases (MMP) in preclinical models. We assessed the effects of doxycycline on progression of arterial calcification in patients enrolled in the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT).

Methods: Two hundred and sixty-one patients were randomized to 100 mg doxycycline twice daily or placebo. Arterial calcification was measured in abdominal vessels on noncontrast computed tomography scans. Patients with baseline computed tomography scan and 1 or more follow-up scans within the 2-year study were included for analysis. For individual arteries, mean change in iliofemoral artery calcification over time was calculated via linear regression. Serum MMP-3 and MMP-9 levels were measured at baseline and 6 months.

Results: Sixty-five patients in the doxycycline and 66 in the placebo arm were included in this analysis. Baseline characteristics between the groups were similar. The unadjusted mean change in iliofemoral calcium score per year trended toward higher values in patients treated with doxycycline compared with placebo (322 ± 399 units/year vs. 217 ± 307 units/year, P = 0.09). After 6 months, changes in serum MMP-3 and MMP-9 levels were not significantly different between study arms.

Conclusions: In patients with small aortic aneurysm, treatment with doxycycline 100 mg twice daily did not decrease circulating levels of the matrix degrading enzymes MMP-3 and 9 or alter the progression of arterial calcification.

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Figures

Figure 1.
Figure 1.
Baseline iliofemoral calcium score, mass, and volume by treatment assignment. Tukey plots display group data, diamonds display outliers defined as 1.5x inter-quartile range, open circles display group means.
Figure 2.
Figure 2.
Representative examples of limited (A) and heavy (B) baseline calcification of iliofemoral arteries. (A) iliofemoral calcification score of 164, (B) iliofemoral calcification score of 5771.
Figure 3.
Figure 3.
Calcium progression in iliofemoral calcium score, mass, and volume by treatment assignment. Calcium progression is estimated using linear regressions completed for each subject for calcium vs. time; slopes are plotted below. Tukey plots display group data, diamonds display outliers defined as 1.5x inter-quartile range, open circles display group means.
Figure 4.
Figure 4.
Percent progression from baseline in iliofemoral calcium score, mass, and volume by treatment assignment. Calcium progression is estimated using linear regressions completed for each subject for calcium vs. time; percent progression (progression slope/baseline calcium x 100%) is plotted below. Tukey plots display group data, diamonds display outliers defined as 1.5x inter-quartile range, open circles display group means.
Figure 5.
Figure 5.
Mean change in iliofemoral calcium score over time based on baseline iliofemoral calcium score.
See this image and copyright information in PMC

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