Pharmacologic Management of Aneurysms

Abstract

Current management of aortic aneurysms relies exclusively on prophylactic operative repair of larger aneurysms. Great potential exists for successful medical therapy that halts or reduces aneurysm progression and hence alleviates or postpones the need for surgical repair. Preclinical studies in the context of abdominal aortic aneurysm (AAA) identified hundreds of candidate strategies for stabilization, and data from pre-operative clinical intervention studies show that interventions in the pathways of the activated inflammatory and proteolytic cascades in enlarging AAA are feasible. Similarly, extensive series of studies in the murine models of Marfan syndromerelated aortapathy inherited aortic root aneurysm support the concept of pharmaceutical aorta stabilization in Marfan syndrome.Although some clinical studies report successful medical stabilization of growing aortic aneurysms and aortic root stabilization in Marfan syndrome, these claims are not consistently confirmed in larger and controlled studies. Consequently, no medical therapy can be recommended for the stabilization of aortic aneurysms.The discrepancy between preclinical successes and clinical trial failures implies shortcomings in the available models of aneurysm disease, and perhaps incomplete understanding of the pathologic processes involved in later stages of aortic aneurysm progression. Preclinical models more reflective of human pathophysiology, identification of biomarkers to predict severity of disease progression, and improved design of clinical trials may more rapidly advance the opportunities in this important field.

Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague-Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

“…Endovascular aneurysm repair (EVAR) is less invasive and generates lower perioperative comorbidity rate than OSR in short-term duration; however, benefits of EVAR are not sustained due to higher reintervention rate and secondary rupture caused by endoleaks or endograft durability [ 3–5 ]. Elegant studies have been conducted aiming to explore candidate drugs for stabilization of aneurysm growth, yet no medical therapy can be recommended [ 6 ]. Hence, new noninvasive alternative strategies are truly needed to halt or reverse aneurysm expansion.…”

Spatial Configuration of Abdominal Aortic Aneurysm Analysis as a Useful Tool for the Estimation of Stent-Graft Migration

“…AAA is a high-risk vascular disease which treatment depends on its diameter. When the diameter is lower than 40 mm pharmacological treatment is applied [ 2 , 3 ], while AAA with diameter equal or above 55 mm and growth rate over 5 mm every 6 months require surgical repair either open or endovascular [ 4 ].…”

Abdominal aortic aneurysms: pathophysiology and clinical issues

“…The lack of any specific, mechanistically based therapeutic strategy, however, underlies how our knowledge is far from being complete and much experimental and clinical work has to be done [2]. The translational gap between the wealth of preclinical successes and clinical failures suggests that available animal models can only be partially representative of human processes and unidentified critical factors need to be still discovered [4]. Answering to these questions and facing unmet clinical needs will require cooperation across disciplines to integrate information from epidemiologic, genetic, genomics, molecular biology and bioengineering studies in experimental and human settings [7].…”