Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm

Sillesen, Henrik; Eldrup, Nikolaj; Hultgren, Rebecka; Lindeman, J.; Bredahl, Kim; Thompson, Matt; Wanhainen, Anders; Wingren, Urban; Swedenborg, Jesper

doi:10.1002/bjs.9824

Cited by 65 publications

(45 citation statements)

References 38 publications

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“…11 Further, AAA patients undergoing treatments with nonsteroidal anti-inflammatory drugs, diuretics, mast cell inhibitors, β blockers, calcium channel blockers, and ACE inhibitors have not exhibited any noteworthy accomplishments. 17,57,155 Other concerns about oral medication therapy for AAA include limitations with respect to current AAA animal models, correct drug dosage, etc . 53 New clinical trials are focusing on the use of anti-angiogenic, 181 anti-platelet, 187 cell-based immunomodulatory, 116 and cyclosporine-based 5 pathways as potential medical therapies for AAA patients.…”

Section: Pgg As a Potential Therapeutic Option For Aaa Patientsmentioning

confidence: 99%

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

et al. 2018

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Pentagalloyl glucose (PGG) is an elastin-stabilizing polyphenolic compound that has significant biomedical benefits, such as being a free radical sink, an anti-inflammatory agent, anti-diabetic agent, enzymatic resistant properties, etc. This review article focuses on the important benefits of PGG on vascular health, including its role in tissue mechanics, the different modes of pharmacological administration (e.g., oral, intravenous and endovascular route, intraperitoneal route, subcutaneous route, and nanoparticle based delivery and microbubble-based delivery), and its potential therapeutic role in vascular diseases such as abdominal aortic aneurysms (AAA). In particular, the use of PGG for AAA suppression and prevention has been demonstrated to be effective only in the calcium chloride rat AAA model. Therefore, in this critical review we address the challenges that lie ahead for the clinical translation of PGG as an AAA growth suppressor.

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Section: Pgg As a Potential Therapeutic Option For Aaa Patientsmentioning

confidence: 99%

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

et al. 2018

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“…7 Thus, ECG-gated imaging may further increase precision by reducing the effects of hemodynamic variations and has been used in clinical trials. 8,18 A rapid increase in AAA diameter (>10 mm/y) is claimed to be a risk factor for rupture 19 and is generally accepted as an indication for repair. 2 The average annual growth rate for AAAs is ≈5% to 10% of the initial diameter; however, there is considerable heterogeneity in growth rates reported across studies.…”

Section: Aaa Diametermentioning

confidence: 99%

“…8,18 A rapid increase in AAA diameter (>10 mm/y) is claimed to be a risk factor for rupture 19 and is generally accepted as an indication for repair.…”

mentioning

confidence: 99%

Surrogate Markers of Abdominal Aortic Aneurysm Progression

Wanhainen

Mani

Golledge

2016

ATVB

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Abstract-The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Wanhainen et al Surrogate Markers of Aneurysm Progression 237in all studies when a standardized protocol is used. 7,8 One of the challenging aspects to assessing maximum AAA diameter is the variety of methods that can potentially be used and the lack of reporting of the exact techniques used in individual studies. Variations may occur in the plane of acquisition (eg, coronal or sagittal), the axis of measurement (eg, axial or orthogonal), the position of the measuring calipers (eg, inner to inner or outer to outer), the relationship with the cardiac cycle (systole versus diastole), and the selected region of the AAA. 9 It has been suggested that diameters measured perpendicular to the aorta centerline (orthogonal), rather than within the axial plane, are more representative of the true AAA diameter. 4,6 With ultrasound, measurements within the anteroposterior, rather than the transverse plane, have been reported to be more reproducible. 4 There is no current consensus on how to place the calipers when measuring the diameter with ultrasound. Methods used include the outer-to-outer method, where calipers are placed on the outer layer of the aortic wall; the inner-to-inner method, where calipers are placed on the inner layer of the aortic wall; and the leading edge-to-leading edge method, where calipers are placed on the outer layer of the anterior wall and the inner layer of the posterior wall ( Figure 1). Much of the reported variation in ultrasound measured AAA diameter is likely because of the variation in caliper placement. 5,10 The UK Small Aneurysm Trial 11 is based on the measurement of AAA diameter on the outer-to-outer method, and this method has been adopted into the current UK intervention criteria. 12 The inner-to-inner method was used in the Multicentre Aneurysm Screening Study, 13 and consequently it is used in the current UK National Health Service AAA screening programme.14 The leading edgeto-leading edge method is used in the current Swedish AAA screening programme.15 Studies comparing these methods show there is a significant difference in diameters measured with the different methods, which has an impact on the reported prevalence rates of AAA. 5,10 In a Swedish AAA screening study, the difference in mean diameter was 4 mm between inner-toinner and outer-to-outer, which resulted in an astonishing 77% difference in AAA prevalence (ie, 1.3% compared with 2.3%). 5A systematic review of 15 studies reported considerable variation in small AAA growth rates (mean, −0.3 to +4.0 mm/y). 15 The variation could not be explained by differences in initial AAA diameter alone. 16 The authors suggested that methodological issues, such as differences in imaging modalities, variation ...

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“…The AORTA trial tested the potential of different doses of pemirolast, a potent mast cell stabilizer [101] in patients with a small aneurysm [102]. Patients underwent strict ultrasound surveillance for 12-months.…”

Section: Doxycycline For Aaa Stabilizationmentioning

confidence: 99%

The pathophysiologic basis of abdominal aortic aneurysm progression: a critical appraisal

Lindeman

2015

Expert Review of Cardiovascular Therapy

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An aneurysm of the abdominal aorta is a common pathology and a major cause of sudden death in the elderly. Currently, abdominal aortic aneurysms (AAAs) can only be treated by surgery and an effective medical therapy is urgently missing. The pathophysiology of AAAs is complex and is believed to be best described as a comprehensive inflammatory response with an accompanying proteolytic imbalance; the latter being held responsible for the progressive weakening of the aortic wall. Remarkably, while interference in inflammatory and/or proteolytic cascades proves highly effective in preclinical studies, emerging clinical studies consistently fail to show a benefit. In fact, some anti-inflammatory interventions appear to adversely influence the disease process. Altogether, recent clinical observations not only challenge the prevailing concepts of AAA progression, but also raise doubt on the translatability of findings from rodent models for growing AAA.

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Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm

Abstract: NCT01354184 (https://www.clinicaltrials.gov).

Cited by 65 publications

References 38 publications

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

Pentagalloyl Glucose and Its Functional Role in Vascular Health: Biomechanics and Drug-Delivery Characteristics

Surrogate Markers of Abdominal Aortic Aneurysm Progression

The pathophysiologic basis of abdominal aortic aneurysm progression: a critical appraisal

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