Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: A Systematic Review and Meta-Analysis

Author(s): Prashanth Rawla*, Marie Line El Helou, Anantha R. Vellipuram.

Journal Name: Cardiovascular & Hematological Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents)

Volume 17 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Objectives: We performed a systematic review and meta-analysis to explore the risk of an aortic aneurysm or aortic dissection following fluoroquinolone administration.

Methods: PubMed, Cochrane library, ClinicalTrials.gov, Embase and Google Scholar were systematically reviewed for controlled studies including adult patients exposed to fluoroquinolones with a primary outcome of aortic aneurysm or aortic dissection.

Results: The meta-analysis was conducted by pooling the effect estimates of four controlled observational studies (one case-control, one case-crossover and two cohort studies). Fluoroquinolone administration more than doubled the risk to develop aortic aneurysm or aortic dissection within 60 days following fluoroquinolone exposure (adjusted Relative Risk [RR] (95% confidence interval [CI]) = 2.14 (1.93 - 2.36); I2 = 15.8%). The quality of the finding was rated as moderate.

The risk increase for aortic aneurysm alone was found to be significant (adjusted RR (95% CI) = 2.23 (2.01 - 2.45); I2 = 0%) while the risk increase for aortic dissection alone was not found to be significant (adjusted RR = 1.88 (0.11 - 3.65); I2 = 74%).

In subgroup analysis, the risk increase for aortic aneurysm or aortic dissection appeared to be higher in females compared to males (RR = 1.87 (1.24 - 2.51); I2 = 0% versus RR = 1.58 (1.25 - 1.92); I2 = 0%, respectively) and higher in older patients compared to younger patients (RR = 1.72 (1.37 - 2.07); I2 = 0% versus RR = 1.47 (0.91 - 2.04); I2 = 0%, respectively).

Subgroup analysis of two studies which measured the duration-response analysis found that as the duration of fluoroquinolone therapy increased from 3 to 14 days to greater than 14 days, there was an increased risk of aortic aneurysm or dissection.

Conclusion: The findings of this meta-analysis confirm the positive association between fluoroquinolones and the development of aortic aneurysm or dissection. The data tend to show that this association may be majorly driven by aortic aneurysm. Additionally, some risk factors appear to prevail including prolonged fluoroquinolone treatment and older age.

Keywords: Adverse reactions, aortic aneurysm, aortic dissection, drug safety, fluoroquinolone, pharmacovigilance.

[1]
Kabbani, S.; Hersh, A.L.; Shapiro, D.J.; Fleming-Dutra, K.E.; Pavia, A.T.; Hicks, L.A. Opportunities to improve fluoroquinolone prescribing in the United States for adult ambulatory care visits. Clin. Infect. Dis., 2018, 67(1), 134-136.
[2]
Stephenson, A.L.; Wu, W.; Cortes, D.; Rochon, P.A. Tendon injury and fluoroquinolone use: A systematic review. Drug Saf., 2013, 36(9), 709-721.
[3]
Kuo, S.C.; Chen, Y.T.; Lee, Y.T.; Fan, N.W.; Chen, S.J.; Li, S.Y.; Liu, C.J.; Chen, T.L.; Chen, T.J.; Fung, C.P. Association between recent use of fluoroquinolones and rhegmatogenous retinal detachment: A population-based cohort study. Clin. Infect. Dis., 2014, 58(2), 197-203.
[4]
Singh, S.; Nautiyal, A. Aortic dissection and aortic aneurysms associated with fluoroquinolones: A systematic review and meta-analysis. Am. J. Med., 2017, 130(12), 1449-1457.
[5]
Michalak, K.; Sobolewska-Wlodarczyk, A.; Wlodarczyk, M.; Sobolewska, J.; Wozniak, P.; Sobolewski, B. Treatment of the fluoroquinolone-associated disability: The pathobiochemical implications. Oxid. Med. Cell. Longev., 2017, 20178023935
[6]
Kaleagasioglu, F.; Olcay, E. Fluoroquinolone-induced tendinopathy: Etiology and preventive measures. Tohoku J. Exp. Med., 2012, 226(4), 251-258.
[7]
Meszaros, I.; Morocz, J.; Szlavi, J.; Schmidt, J.; Tornoci, L.; Nagy, L.; Szep, L. Epidemiology and clinicopathology of aortic dissection. Chest, 2000, 117(5), 1271-1278.
[8]
Nordon, I.M.; Hinchliffe, R.J.; Loftus, I.M.; Thompson, M.M. Pathophysiology and epidemiology of abdominal aortic aneurysms. Nat. Rev. Cardiol., 2011, 8(2), 92-102.
[9]
Kuivaniemi, H.; Ryer, E.J.; Elmore, J.R.; Tromp, G. Understanding the pathogenesis of abdominal aortic aneurysms. Expert Rev. Cardiovasc. Ther., 2015, 13(9), 975-987.
[10]
Johnston, K.W.; Rutherford, R.B.; Tilson, M.D.; Shah, D.M.; Hollier, L.; Stanley, J.C. Suggested standards for reporting on arterial aneurysms. J. Vasc. Surg., 1991, 13(3), 452-458.
[11]
Ashley, E.A.; Niebauer, J. In: . Cardiology Explained; London, 2004.
[12]
Melvinsdottir, I.H.; Lund, S.H.; Agnarsson, B.A.; Sigvaldason, K.; Gudbjartsson, T.; Geirsson, A. The incidence and mortality of acute thoracic aortic dissection: Results from a whole nation study. Eur. J. Cardiothorac. Surg., 2016, 50(6), 1111-1117.
[13]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; Group, P. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med., 2009, 6(7)e1000097
[14]
Wells, G.A.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa:; Ottawa Hospital Research Institute, 2011.
[15]
Neyeloff, J.L.; Fuchs, S.C.; Moreira, L.B. Meta-analyses and forest plots using a microsoft excel spreadsheet: Step-by-step guide focusing on descriptive data analysis. BMC Res. Notes, 2012, 5, 52.
[16]
Ryan, R.H.S. How to GRADE the quality of the evidence., Cochrane Consumers and Communication Group. . (15 June).
[17]
Daneman, N.; Lu, H.; Redelmeier, D.A. Fluoroquinolones and collagen associated severe adverse events: A longitudinal cohort study. BMJ Open, 2015, 5(11)e010077
[18]
Pasternak, B.; Inghammar, M.; Svanstrom, H. Fluoroquinolone use and risk of aortic aneurysm and dissection: Nationwide cohort study. BMJ, 2018, 360, k678.
[19]
Lee, C.C.; Lee, M.T.; Chen, Y.S.; Lee, S.H.; Chen, Y.S.; Chen, S.C.; Chang, S.C. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern. Med., 2015, 175(11), 1839-1847.
[20]
Lee, C.C.; Lee, M.G.; Hsieh, R.; Porta, L.; Lee, W.C.; Lee, S.H.; Chang, S.S. Oral fluoroquinolone and the risk of aortic dissection. J. Am. Coll. Cardiol., 2018, 72(12), 1369-1378.
[21]
Braverman, A.C. Acute aortic dissection clinician update. Circulation, 2010, 122, 184-188.
[22]
Kuivaniemi, H.; Ryer, E.J.; Elmore, J.R.; Tromp, G. Understanding the pathogenesis of abdominal aortic aneurysms. Expert Rev. Cardiovasc. Ther., 2015, 13(9), 975-987.
[23]
Qin, P.; Liu, R. Oxidative stress response of two fluoroquinolones with catalase and erythrocytes: A combined molecular and cellular study. J. Hazard. Mater., 2013, 252-253, 321-329.
[24]
Tsai, W.C.; Hsu, C.C.; Chen, C.P.; Chang, H.N.; Wong, A.M.; Lin, M.S.; Pang, J.H. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J. Orthop. Res., 2011, 29(1), 67-73.
[25]
Badal, S.; Her, Y.F.; Maher, L.J. Nonantibiotic effects of fluoroquinolones in mammalian cells. J. Biol. Chem., 2015, 290(36), 22287-22297.
[26]
Fan, L.M.; Douglas, G.; Bendall, J.K.; McNeill, E.; Crabtree, M.J.; Hale, A.B.; Mai, A.; Li, J.M.; McAteer, M.A.; Schneider, J.E.; Choudhury, R.P.; Channon, K.M. Endothelial cell-specific reactive oxygen species production increases susceptibility to aortic dissection. Circulation, 2014, 129(25), 2661-2672.
[27]
Shen, M.; Lee, J.; Basu, R.; Sakamuri, S.S.; Wang, X.; Fan, D.; Kassiri, Z. Divergent roles of matrix metalloproteinase 2 in pathogenesis of thoracic aortic aneurysm. Arteriosc. Thromb. Vasc. Biol., 2015, 35(4), 888-898.
[28]
LeMaire, S.A.; Zhang, L.; Luo, W.; Ren, P.; Azares, A.R.; Wang, Y.; Zhang, C.; Coselli, J.S.; Shen, Y.H. Effect of ciprofloxacin on susceptibility to aortic dissection and rupture in mice. JAMA Surg., 2018, 153(9)e181804
[29]
Guzzardi, D.G.; Teng, G.; Kang, S.; Geeraert, P.J.; Pattar, S.S.; Svystonyuk, D.A.; Belke, D.D.; Fedak, P.W.M. Induction of human aortic myofibroblast-mediated extracellular matrix dysregulation: A potential mechanism of fluoroquinolone associated aortopathy. J. Thorac. Cardiovasc. Surg., 2019, 157(1), 109-119.
[30]
Guo, Y.; Bai, Y.; Yang, C.; Wang, P.; Gu, L. Mycotic aneurysm due to Salmonella species: Clinical experiences and review of the literature. Braz. J. Med. Biol. Res., 2018, 51(9)e6864
[31]
Yaguea, M.; Tempranoa, I.; Losab, J.; De Benitoc, L.; De La Cruzd, R.; Cheynee, N.; Henriquez, C. Staphylococcus aureus aortitis and retroperitoneal fibrosis: A case report and literature review. IDCases, 2016, 5, 60-62.
[32]
Gardiner, B.J.; Wong, J.; Yii, M.; Buckenham, T.; Korman, T.M. Streptococcus pyogenes aortic aneurysm infection: Forgotten but not gone. Infect. Dis. Rep., 2013, 5(11), 37-39.
[33]
Hinterseher, I.; Gabel, G.; Corvinus, F.; Saeger, H.D.; Bergert, H.; Tromp, G.; Kuivaniemi, H. Presence of Borrelia burgdorferi sensu lato antibodies in the serum of patients with abdominal aortic aneurysms. Eur. J. Clin. Microbiol. Infect. Dis., 2012, 31(5), 781-789.
[34]
Morales, D.R.; Slattery, J.; Pacurariu, A.; Pinhiro, L.; McGettigan, P.; Kurz, X. Relative and absolute risk of tendon rupture with fluoroquinolone and concomitant fluoroquinolone/corticosteroid therapy: Population-based nested case-control study. Clin. Drug Investig., 2019, 39, 205-213.
[35]
Khaliq, Y.; Zhanel, G.G. Fluoroquinolone-associated tendinopathy: A critical review of the literature. Clin. Infect. Dis., 2003, 36(11), 1404-1410.
[36]
Persson, R.; Jick, S. Clinical implications of the association between fluoroquinolones and tendon rupture: The magnitude of the effect with and without corticosteroids. Br. J. Clin. Pharmacol., 2019.
[http://dx.doi.org/10.1111/bcp.13879]
[37]
Nyyssönen, T.; Lantto, I.; Lüthje, P.; Selander, T.; Kröger, H. Drug treatments associated with Achilles tendon rupture. A casecontrol study involving 1118 Achilles tendon ruptures. Scand. J. Med. Sci. Sports, 2018, 28(12), 2625-2629.
[38]
Wise, B.L.; Peloquin, C.; Choi, H.; Lane, N.E.; Zhang, Y. Impact of age, sex, obesity, and steroid use on quinolone-associated tendon disorders. Am. J. Med., 2012, 125(12), 23-28.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 1
Year: 2019
Page: [3 - 10]
Pages: 8
DOI: 10.2174/1871525717666190402121958

Article Metrics

PDF: 50
HTML: 7
EPUB: 2
PRC: 1