Pharmacological approaches to prevent abdominal aortic aneurysm enlargement and rupture

Current efforts to limit the mortality from abdominal aortic aneurysm (AAA) are dependent on detection and elective repair. Even by conservative estimates, there are more than 300,000 undetected AAAs in the United States, most of which are small and would not require immediate intervention. Current practice following detection of a small AAA includes education, risk factor management, and serial observation. This approach, based on the statistical probability of death from rupture compared to the morbidity and mortality of repair, can be unsettling to patients and lead to a decline in perceived quality of life. While the pathophysiology of AAA is not completely understood, observations from human tissues and animal studies have identified a number of potential targets for inhibiting aneurysm expansion. It is clear that the prominent inflammatory response identified in aneurysm tissue has a role in promoting aortic expansion. This inflammatory response is thought to account for increased expression of proteolytic enzymes. Recent work has suggested a unifying hypothesis centered on the MAP kinase family affecting both the regulation of matrix synthesis and the expression of proteolytic enzymes. The tetracycline antibiotics and antihypertensive medications that affect the angiotensin-converting enzyme system can inhibit proteolysis. There are adequate preliminary data to support a large prospective randomized trial of doxycycline to prevent aneurysm expansion.