Lack of an effective drug therapy for abdominal aortic aneurysm

被引:107
作者
Golledge, J. [1 ,2 ,3 ]
Moxon, J. V. [1 ,3 ]
Singh, T. P. [1 ,2 ]
Bown, M. J. [4 ,5 ]
Mani, K. [6 ]
Wanhainen, A. [6 ]
机构
[1] James Cook Univ, Queensland Res Ctr Peripheral Vasc Dis, Coll Med & Dent, Townsville, Qld 4811, Australia
[2] Townsville Hosp, Dept Vasc & Endovasc Surg, Townsville, Qld, Australia
[3] James Cook Univ, Ctr Mol Therapeut, Australian Inst Trop Hlth & Med, Townsville, Qld, Australia
[4] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England
[5] Univ Leicester, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England
[6] Uppsala Univ, Dept Surg Sci, Vasc Surg, Uppsala, Sweden
基金
英国医学研究理事会;
关键词
aneurysm; aortic; medication; meta-analysis; systematic review; RANDOMIZED CLINICAL-TRIAL; DOUBLE-BLIND; GROWTH-RATE; CHLAMYDIA-PNEUMONIAE; DOXYCYCLINE; ASSOCIATION; PREVALENCE; PLACEBO; SURVEILLANCE; METAANALYSIS;
D O I
10.1111/joim.12958
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. CurrentAAAtreatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing smallAAA. This review summarizes priorAAApathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo-controlled drug trials in patients with smallAAAs. Eleven previously published randomized-controlled clinical trials testing different drug therapies aimed at slowingAAAprogression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta-analyses of these trials suggested that neither of these approaches limitAAAgrowth. Allocation to blood pressure-lowering medication was associated with a small reduction inAAArupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00,P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect onAAAgrowth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow-up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy forAAAis to be identified.
引用
收藏
页码:6 / 22
页数:17
相关论文
共 69 条
[1]   Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content [J].
Abdul-Hussien, Hazem ;
Hanemaaijer, Roeland ;
Verheijen, Jan H. ;
van Bockel, J. Hajo ;
Geelkerken, Robert H. ;
Lindeman, Jan H. N. .
JOURNAL OF VASCULAR SURGERY, 2009, 49 (03) :741-749
[2]   Risk Factors for Abdominal Aortic Aneurysm in Population-Based Studies: A Systematic Review and Meta-Analysis [J].
Altobelli, Emma ;
Rapacchietta, Leonardo ;
Profeta, Valerio F. ;
Fagnano, Roberto .
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 2018, 15 (12)
[3]   Non-invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT): Design of a Phase IIb, placebo-controlled, double-blind, randomized clinical trial of doxycycline for the reduction of growth of small abdominal aortic aneurysm [J].
Baxter, B. Timothy ;
Matsumura, Jon ;
Curci, John ;
McBride, Ruth ;
Blackwelder, William C. ;
Liu, Xinggang ;
Larson, LuAnn ;
Terrin, Michael L. .
CONTEMPORARY CLINICAL TRIALS, 2016, 48 :91-98
[4]   An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK) [J].
Bicknell, Colin D. ;
Kiru, Gaia ;
Falaschetti, Emanuela ;
Powell, Janet T. ;
Poulter, Neil R. .
EUROPEAN HEART JOURNAL, 2016, 37 (42) :3213-3221
[5]   Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair [J].
Brittenden, Julie ;
Houston, Graeme ;
Lambie, Robert ;
Norrie, John ;
McBride, Olivia ;
Forsythe, Rachael ;
Newby, David ;
McKillop, Graham ;
Semple, Scott ;
Burns, Paul ;
Berry, Colin ;
Murray, Gordon ;
Wee, Fiona .
CIRCULATION, 2017, 136 (09) :787-797
[6]   Comparison of Surveillance Versus Aortic Endografting for Small Aneurysm Repair (CAESAR): Results from a Randomised Trial [J].
Cao, P. ;
De Rango, P. ;
Verzini, F. ;
Parlani, G. ;
Romano, L. ;
Cieri, E. .
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, 2011, 41 (01) :13-25
[7]   The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm [J].
Chaikof, Elliot L. ;
Dalman, Ronald L. ;
Eskandari, Mark K. ;
Jackson, Benjamin M. ;
Lee, W. Anthony ;
Mansour, M. Ashraf ;
Mastracci, Tara M. ;
Mell, Matthew ;
Murad, M. Hassan ;
Nguyen, Louis L. ;
Oderich, Gustavo S. ;
Patel, Madhukar S. ;
Schermerhorn, Marc L. ;
Starnes, Benjamin W. .
JOURNAL OF VASCULAR SURGERY, 2018, 67 (01) :2-+
[8]   A Targeting Nanotherapy for Abdominal Aortic Aneurysms [J].
Cheng, Juan ;
Zhang, Runjun ;
Li, Chenwen ;
Tao, Hui ;
Dou, Yin ;
Wang, Yuquan ;
Hu, Houyuan ;
Zhang, Jianxiang .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2018, 72 (21) :2591-2605
[9]   Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians [J].
Davies, Neil M. ;
Holmes, Michael V. ;
Smith, George Davey .
BMJ-BRITISH MEDICAL JOURNAL, 2018, 362
[10]  
Dodd BR, 2011, CURR VASC PHARMACOL, V9, P471