Intermittent Roxithromycin for Preventing Progression of Small Abdominal Aortic Aneurysms: Long-Term Results of a Small Clinical Trial

Abstract

Background: Antibodies against Chlamydia pneumoniae are associated with an increased rate of expansion of small abdominal aortic aneurysms (AAAs). Short-term follow-up trials have shown a transient reduction AAA growth rate, in macrolide treated compared with placebo. Therefore we analysed the influence of intermittent, long-term roxithromycin treatment on AAA expansion and referral for surgery. Methods: Eighty-four patients with small AAAs were randomized to either an annual 4 weeks’ treatment with roxithromycin or placebo, and followed prospectively. Results: Intermittent, long-term Roxithromycin-treatment reduced mean annual growth rate by 36% compared with placebo after adjustment for potential confounders. Long-term roxithromycin-treated patients had a 29% lower risk of being referred for surgical evaluation, increasing to 57% after adjusting for potential confounders. Conclusion: Annual 4 week treatment with 300 mg roxithromycin daily may reduce the progression of small AAAs, and later need for surgical repair. However, more robust studies are needed for confirmation.

Keywords

abdominal aortic aneurysm macrolide prophylactic medicine long-term follow-up

Get full access to this article

View all access options for this article.

References

Ernst CB Abdominal aortic aneurysm. N Engl J Med. 1993 ;328(17):1167-1172.

Lindholt JS , Fasting H. , Henneberg EW , Ostergaard L. A review of Chlamydia pneumonia and atherosclerosis. Eur J Vasc Endovasc Surg. 1999;17:283-289.

Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med. 1999;340(2):115-126.

Libby P. , Ridker PM , Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-1143.

Lindholt JS , Ashton HA , Scott RA Indicators of infection with Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysms. J Vasc Surg. 2001;34(2):212-215.

Halme S. , Juvonen T. , Laurila A. , et al. Chlamydia pneumoniae reactive T lymphocytes in the walls of abdominal aortic aneurysms. Eur J Clin Invest. 1999;29(6):546-52.

LaBiche R. , Koziol D. , Quinn TC , et al. Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque. Stroke. 2001 ;32(4): 855-860.

Kaperonis EA , Liapis CD , Kakisis JD , Perrea D. , Kostakis AG , Karayannakos PE The association of carotid plaque inflammation and Chlamydia pneumoniae infection with cerebrovascular symptomatology. J Vasc Surg. 2006;44(6):1198-204.

Kaperonis EA , Liapis CD , Kakisis JD , et al. Inflammation and Chlamydia pneumoniae infection correlate with the severity of peripheral arterial disease. Eur J Vasc Endovasc Surg. 2006;31(5):509-515.

10.

Cannon CP , Braunwald E. , McCabe CH , et al. Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome. N Engl J Med. 2005;352(16):1646-1654.

11.

Grayston JT Antibiotic treatment of atherosclerotic cardiovascular disease. Circulation. 2003;107(9):1228-1230.

12.

Elkind MS , Lin IF , Grayston JT , Sacco RL Chlamydia pneumoniae and the risk of first ischemic stroke: The Northern Manhattan Stroke Study. Stroke. 2000;31(7): 1521-1525.

13.

Lindholt JS , Juul S. , Vammen S. , Lind I. , Fasting H. , Henneberg EW. Immunoglobulin A antibodies against Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysm. Br J Surg. 1999;86(5): 634-638.

14.

Pyo R. , Lee JK , Shipley JM , et al. Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J Clin Invest. 2000;105(11): 1641-1649.

15.

Curci JA , Petrinec D. , Liao S. , Golub LM , Thompson RW Pharmacologic suppression of experimental abdominal aortic aneurysms: a comparison of doxycycline and four chemically modified tetracyclines. J Vasc Surg. 1998;28(6):1082-1093.

16.

Kol A. , Sukhova GK , Lichtman AH , Libby P. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression . Circulation. 1998; 98(4):300-307.

17.

Thompson RW , Baxter BT MMP inhibition in abdominal aortic aneurysms. Rationale for a prospective randomized clinical trial. Ann N Y Acad Sci. 1999;878:159-178.

18.

Boyle JR , McDermott E. , Crowther M. , Wills AD , Bell PR , Thompson MM Doxycycline inhibits elastin degradation and reduces metalloproteinase activity in a model of aneurysmal disease. J Vasc Surg. 1998;27(2):354-361.

19.

Lindholt JS , Juul S. , Fasting H. , Henneberg EW Screening for abdominal aortic aneurysms: single centre randomised controlled trial. BMJ. 2005; 330(7494):750.

20.

Sterpetti AV , Cavallaro A. , Cavallari N. , et al. Factors influencing the rupture of abdominal aortic aneurysms. Surg Gynecol Obstet. 1991;173(3):175-178.

21.

Cronenwett JL , Sargent SK , Wall MH , et al. Variables that affect the expansion rate and outcome of small abdominal aortic aneurysms. J Vasc Surg. 1990;11(2): 260-268.

22.

Bengtsson H. , Nilsson P. , Bergqvist D. Natural history of abdominal aortic aneurysm detected by screening. Br J Surg. 1993;80(6):718-720.

23.

Bengtsson H. , Bergqvist D. , Ekberg O. , Ranstam J. Expansion pattern and risk of rupture of abdominal aortic aneurysms that were not operated on. Eur J Surg. 1993;159(9):461-467.

24.

Collin J. , Heather B. , Walton J. Growth rates of subclinical abdominal aortic aneurysms-implications for review and rescreening programmes. Eur J Vasc Surg. 1991; 5(2):141-144.

25.

Vammen S. , Lindholt JS , Ostergaard L. , Fasting H. , Henneberg EW Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion. Br J Surg. 2001;88(8):1066-1072.

26.

Lindholt JS , Stovring J. , Andersen PL , Henneberg EW , Ostergaard L. A review of macrolide treatment of atherosclerosis and abdominal aortic aneurysms. Curr Drug Targets Infect Disord . 2003;3(1):55-63.

27.

Baxter BT , Pearce WH , Waltke EA , et al. Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study. J Vasc Surg. 2002;36(1):1-12.

28.

Gieffers J. , Fullgraf H. , Jahn J. , et al. Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment. Circulation. 2001;103(3): 351-356.

29.

Mpiga P. , Ravaoarinoro M. Effects of sustained antibiotic bactericidal treatment on Chlamydia trachomatisinfected epithelial-like cells (HeLa) and monocyte-like cells (THP-1 and U-937). Int J Antimicrob Agents. 2006;27(4):316-324.

30.

Lindholt JS , Vammen S. , Juul S. , Henneberg EW , Fasting H. The validity of ultrasonographic scanning as screening method for abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 1999;17(6):472-475.