Abdominal Aortic Aneurysms Pharmacoepidemiological Studies.

An abdominal aortic aneurysm (AAA) is an enlargement of the abdominal aorta. It is a common disease in the elderly, with a prevalence of 1-5%. An AAA is normally asymptomatic, and the diagnosis is often incidental, identified when a patient is examined for other conditions. The major risk of having an AAA is sudden rupture and death caused by massive hemorrhaging. As rupture risk increases with increasing AAA diameter, the current management strategies include regular imaging surveillance and elective repair before rupture occurs. Ruptured AAA (rAAA) carries high mortality, and an identification of a drug or compound with the potential to halt the growth of an AAA and/or reduce the risk of a rAAA is needed. Thus, the aims of this thesis were to examine the clinical impact of treatment with statins (Study I), reninangiotensin system (RAS) blockers (Study II), and low-dose aspirin (ASA)(Study III) on the risk of rAAA and case fatality following rAAA. The thesis is based on three nation-wide, combined case-control and follow-up studies using data from Danish population-based health-care and administrative registries. In Study I (1996-2008), we included 3,691 patients with an incident diagnosis of rAAA (cases). For the risk analyses, we matched 3,584 rAAA cases to 3,584 age- and sex-matched patients with an incident diagnosis of AAA (controls). Current statin use was associated with a lower risk of rAAA, adjusted odds ratio (OR): 0.73 (95% CI: 0.61;0.86), compared to never use of statins. Furthermore, current statin use was associated with a lower 30-day case fatality following rAAA, adjusted mortality rate ratio (MRR): 0.80 (95% CI: 0.68;0.95). In Study II (1996-2012), we identified 4,052 rAAA cases and 10,549 AAA controls. We were unable to demonstrate any association between the current use of either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers and the risk of rAAA, adjusted ORs: 0.96 (95% CI: 0.85;1.07) and 0.93 (95% CI: 0.79;1.09), respectively. The results were robust in supplemental propensity score matched analyses. Likewise, no association between current use of RAS-blockers and 30-day case fatality was found. In Study III (1996-2012), 4,055 rAAA cases were included. The adjusted OR for the risk of rAAA in ASA users compared to non-users was 0.97 (95% CI: 0.86;1.08). However, ASA use was associated with an unfavorable 30-day case fatality, adjusted MRR 1.17 (95% CI: 1.06;1.28), corresponding to an excessive rAAA case fatality in ASA users of nearly 20%. In conclusion, we found an approximately 25% lower risk of rAAA and 20% lower 30-day case fatality in statin-treated patients. Furthermore, we found an almost 20% higher 30-day case fatality following rAAA in ASA treated patients. No association between the use of RAS-blockers and the risk of rAAA or case fatality following rAAA was found. Similarly, we found no association between the use of ASA and the risk of rAAA.