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7. Impact of abdominal aortic aneurysm screening on quality of life

Author

Bath, M. F., Sidloff, D., Saratzis, A., Bown, M. J., Pathak, R., Brooks, M., Hayes, P., Imray, C., Quarmby, J., Choksy, S., Earnshaw, J. J., Shearman, C. P., Grocott, E., Rix, T., Chetter, I., Tennant, W., Libertiny, G., Sykes, T., Dayer, M., Pike, L., Pherwani, A., Nice, C., Browning, N., McCollum, C., Yusuf, S., Gannon, M., Barwell, J., Baker, S., Vallabhaneni, S. R., and Davies, A.

Published
2018
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14. Individual-patient meta-analysis of three randomized trials comparing endovascular versus open repair for ruptured abdominal aortic aneurysm

Author

Sweeting, M. J., Balm, R., Desgranges, P., Ulug, P., Powell, J. T., Koelemay, M. J. W., Idu, M. M., Kox, C., Legemate, D. A., Huisman, L. C., Willems, M. C. M., Reekers, J. A., van Delden, O. M., van Lienden, K. P., Hoornweg, L. L., Reimerink, J. J., van Beek, S. C., Vahl, A. C., Leijdekkers, V. J., Bosma, J., Montauban van Swijndregt, A. D., de Vries, C., van der Hulst, V. P. M., Peringa, J., Blomjous, J. G. A. M., Visser, M. J. T., van der Heijden, F. H. W. M., Wisselink, W., Hoksbergen, A. W. J., Blankensteijn, J. D., Visser, M. T. J., Coveliers, H. M. E., Nederhoed, J. H., van den Berg, F. G., van der Meijs, B. B., van den Oever, M. L. P., Lely, R. J., Meijerink, M. R., Voorwinde, A., Ultee, J. M., van Nieuwenhuizen, R. C., Dwars, B. J., Nagy, T. O. M., Tolenaar, P., Wiersema, A. M., Lawson, J. A., van Aken, P. J., Stigter, A. A., van den Broek, T. A. A., Vos, G. A., Mulder, W., Strating, R. P., Nio, D., Akkersdijk, G. J. M., van der Elst, A., van Exter, P., Becquemin, J.-P., Allaire, E., Cochennec, F., Marzelle, J., Louis, N., Schneider, J., Majewski, M., Castier, Y., Leseche, G., Francis, F., Steinmetz, E., Berne, J.-P., Favier, C., Haulon, S., Koussa, M., Azzaoui, R., Piervito, D., Alimi, Y., Boufi, M., Hartung, O., Cerquetta, P., Amabile, P., Piquet, P., Penard, J., Demasi, M., Alric, P., Canaud, L., Berthet, J.-P., Julia, P., Fabiani, J.-N., Alsac, J. M., Gouny, P., Badra, A., Braesco, J., Favre, J.-P., Albertini, J.-N., Martinez, R., Hassen-Khodja, R., Batt, M., Jean, E., Sosa, M., Declemy, S., Destrieux-Garnier, L., Lermusiaux, P., Feugier, P., Ashleigh, R., Gomes, M., Greenhalgh, R. M., Grieve, R., Hinchliffe, R., Sweeting, M., Thompson, M. M., Thompson, S. G., Cheshire, N. J., Boyle, J. R., Serracino-Inglott, F., Smyth, J. V., Hinchliffe, R. J., Bell, R., Wilson, N., Bown, M., Dennis, M., Davis, M., Howell, S., Wyatt, M. G., Valenti, D., Bachoo, P., Walker, P., MacSweeney, S., Davies, J. N., Rittoo, D., Parvin, S. D., Yusuf, W., Nice, C., Chetter, I., Howard, A., Chong, P., Bhat, R., McLain, D., Gordon, A., Lane, I., Hobbs, S., Pillay, W., Rowlands, T., El-Tahir, A., Asquith, J., Cavanagh, S., Dubois, L., and Forbes, T. L.

Published
2015
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22. Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm

Author

Golledge, J, Arnott, C, Moxon, J, Monaghan, H, Norman, R, Morris, D, Li, Q, Jones, G, Roake, J, Bown, M, Neal, B, Golledge, J, Arnott, C, Moxon, J, Monaghan, H, Norman, R, Morris, D, Li, Q, Jones, G, Roake, J, Bown, M, and Neal, B

Abstract

Background: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. Methods: MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). Discussion: Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. Trial registration: Aust

Published
2021

31. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author

BAKKER, M. K., VAN DER SPEK, R. A. A., VAN RHEENEN, W., Morel, S., Bourcier, R., HOSTETTLER, I. C., ALG, V. S., VAN EIJK, K. R., KOIDO, M., Akiyama, M., TERAO, C., Matsuda, K., WALTERS, R. G., Lin, K., Li, L., MILLWOOD, I. Y., Chen, Z., Rouleau, G. A., Zhou, S., RANNIKMAE, K., SUDLOW, C. L. M., Houlden, H., VAN DEN BERG, L. H., Dina, C., Naggara, O., GENTRIC, J. C., Shotar, E., Eugene, F., DESAL, H., WINSVOLD, B. S., BORTE, S., JOHNSEN, M. B., BRUMPTON, B. M., SANDVEI, M. S., WILLER, C. J., Hveem, K., ZWART, J. A., VERSCHUREN, W. M. M., Friedrich, C. M., Hirsch, S., Schilling, S., DAUVILLIER, J., Martin, O., Jones, G. T., BOWN, M. J., KO, N. U., Kim, H., COLEMAN, J. R. I., Breen, G., ZAROFF, J. G., KLIJN, C. J. M., Malik, R., DICHGANS, M., Sargurupremraj, Muralidharan, Tatlisumak, T., Amouyel, P., Debette, Stephanie, RINKEL, G. J. E., WORRALL, B. B., Pera, J., SLOWIK, A., GAAL-PAAVOLA, E. I., NIEMELA, M., JAASKELAINEN, J. E., VON UND ZU FRAUNBERG, M., LINDGREN, A., BRODERICK, J. P., WERRING, D. J., Woo, D., REDON, R., Bijlenga, P., Kamatani, Y., VELDINK, J. H., RUIGROK, Y. M., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, cardiovascular diseases
Abstract

Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Published
2020
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35. Lack of an effective drug therapy for abdominal aortic aneurysm

Author

Golledge, J., Moxon, J. V., Singh, T. P., Bown, M. J., Mani, Kevin, Wanhainen, Anders, Golledge, J., Moxon, J. V., Singh, T. P., Bown, M. J., Mani, Kevin, and Wanhainen, Anders

Abstract

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.

Published
2020
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