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Ace Inhibitors for Abdominal Aortic Aneurysms
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Synopsis: ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.
Source: Hackam DG, et al. Angiotensin-Converting Enzyme Inhibitors and Aortic Rupture: A Population-Based Case-Control Study. Lancet. 2006;368:659-665.
Rupture of an abdominal aortic aneurysm (AAA) is a lethal complication of this relatively common (5% of men > 50 years of age) condition. Currently, early surgery is the only known preventative measure. Animal studies suggest a role for angiotensin II in the pathogenesis of AAA, and ACE inhibitors have been shown an ability to prevent aortic expansion and rupture. Other antihypertensive drugs were not effective, suggesting that this effect may be independent of blood pressure reductions. Thus, Hackam and colleagues performed a retrospective, case-controlled study of ACE inhibitor use in AAA patients in Ontario Province, Canada.
A database was used to identify 15,326 patients age 65 or older who were hospitalized with a primary diagnosis of intact or ruptured AAA over 10 years (1992-2002). The primary exposure was ACE inhibitor treatment before hospitalization derived from pharmacy records and defined as 2 or more prescriptions in the year before admission with 1 within 3 months of admission. Logistic regression analysis was used to compute any association between ACE inhibitor use and AAA rupture, and multivariate analyses were used to assess the effects of confounders. Also, the exposure to 5 other antihypertensive drug classes was assessed in a similar fashion.
Results: Rupture occurred in 22% of the patients with a mean age of 75 years; 78% were men. Ace inhibitors before admission were found in 22% of the total population, and the indications for their use between the rupture and no rupture groups was the same. Patients receiving ACE Inhibitors had an 18% lower risk of rupture (OR, 0.82; CI, 0.74-0.90; P < 0.0001). Adjustment for confounders did not appreciably alter the results. The benefit was not related to ACE inhibitor dose or type of ACE inhibitor. Discontinuation of ACE inhibitor before admission abrogated the benefits. Ace inhibitors were effective in all pre-specified subgroups. Other antihypertensive agents were not associated with a reduced risk of rupture. Hackman et al concluded that ACE inhibitors are associated with a reduced risk of AAA rupture.
Here is another study attempting to broaden the indications for ACE inhibitors. This study is based upon solid pre-clinical data. It showed benefit if you were taking ACE inhibitors and none if you discontinued them. The benefit was not seen with other classes of drugs. The main issue in any case-controlled study is selection bias. This is a hospital-based study, so those who ruptured out of the hospital are not included. Perhaps those on ACE inhibitors were healthier in general and less likely to rupture. Against this is that there was no difference in the indications and contraindications for ACE inhibitors between those taking and not taking them. Also, adjustment for comorbidities and other confounders did not change the results. Thus, the data seem solid.
The fact that other antihypertensives were not associated with this benefit suggests that the beneficial effect is due to some other effect of blocking the renin-angiotensin system. Unfortunately, there is no blood pressure data in this study. Also, no dose response to ACE inhibitors was seen, suggesting that the effect is not related to blood pressure lowering. There was insufficient data in the study to ascertain if the effect is also seen with angiotensin receptor blockers.
The management of AAA is now predicated on following the diameter of the aorta and recommending surgery or endovascular repair for certain sizes. Although I would not prescribe ACE inhibition instead of surgery for those with large aneurysms, I certainly would try to get those who are not surgical candidates on ACE inhibitors, based upon this data. Since the effect was not dose related, the minimal tolerated dose would probably be adequate.