Up to 8 percent of men older than 50 years develop aortic aneurysms. Without treatment, approximately one third of aneurysms rupture, and one half of these patients die before admission to the hospital. The total mortality rate after rupture is 80 to 90 percent. The mortality rate of elective repair of aneurysms before rupture is approximately 5 percent, and the overall complication rate is around 32 percent. The risk of developing aortic aneurysm or other cardiovascular abnormalities has been linked to the renin-angiotensin system, which also has been implicated in aneurysm rupture. Hackam and colleagues studied the potentially beneficial effect of angiotensin-converting enzyme (ACE) inhibitors on the risk of aortic aneurysm rupture.
In this population-based case-control study, researchers used several health databases covering the population of Ontario, Canada. These sources provided comprehensive health information (e.g., prescription use, hospital admission, procedures and surgeries, causes of mortality) on approximately 12 million persons over a 10-year period. The researchers identified persons who received prescriptions for any of the 10 ACE inhibitor drugs available in Ontario during the study. They also identified all patients older than 65 years who were admitted to the hospital because of abdominal aortic aneurysm. Demographic data, major comorbidities, risk factors for rupture, and contraindications to ACE inhibitor use also were measured. The statistical analysis examined the association of ACE inhibitor use with aortic rupture.
During the study, 15,326 patients were admitted to the hospital with a primary diagnosis of abdominal aortic aneurysm. Overall, 78 percent were men, and the mean age was 75 years. The aneurysm had ruptured in 3,379 (22 percent) of patients. Patients with ruptured aneurysms were put into one group, and the other 11,947 patients with unruptured aneurysms were in the control group. Less than 2 percent of all patients had contraindications to ACE inhibitors, and the two groups were balanced in indications for use of these drugs. The groups also had comparable measures of general health.
Therapy with ACE inhibitors was documented in 665 patients with ruptures (20 percent) and in 2,761 persons in the control group (23 percent). Patients receiving ACE inhibitors had an 18 percent lower chance of aortic rupture. This finding remained significant after adjusting for demographic factors, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, health care usage, and screening history. The protective effect was only slightly lower for patients taking the lowest available dose of ACE inhibitors and was equivalent for each of the three most common agents used (enalapril [Vasotec], lisinopril [Zestril], and ramipril [Altace]). Patients who discontinued ACE inhibitor therapy were not protected from rupture. No protective effect was associated with any other antihypertensive treatments used by patients or with any of the six most common nonantihypertensive drugs that were evaluated.
The authors conclude that the use of ACE inhibitors is associated with a reduced risk of abdominal aortic aneurysm rupture. This protection is likely a result of direct beneficial effects that ACE inhibitors have on the vessel wall. Although reduction in blood pressure could contribute to stabilizing an aneurysm, other antihypertensive agents provided no protective effect. The authors call for larger randomized controlled trials of this therapy.