An analysis of drug modulation of abdominal aortic aneurysm growth through 25 years of surveillance.

BACKGROUND: A modest (41%) reduction in abdominal aortic aneurysm (AAA) growth rate is likely to delay AAA-related events (surgery or rupture) by 5 years, making the notion of AAA medical treatment very appealing. Randomized controlled trials of commonly used existing medications are expensive and ethically questionable. This study reviewed the independent associations of commonly used medications and AAA growth during a 25-year period of AAA surveillance. METHODS: The study included all patients monitored through an AAA screening and surveillance program. Records of AAA size, risk factors, outcomes, death, and medications were entered into a continually updated database. AAA growth rates were calculated using a flexible hierarchical model. A multivariate model was used to test for associations independent of confounders. RESULTS: The study comprised 1269 patients (94.1% men) who had a mean age of 67 years. The median starting diameter was 35 mm, the end diameter was 44 mm, and follow-up was 3.4 years. Drugs used in the treatment of diabetes were associated with a 56% reduction in AAA growth rate (P = .01) independent of confounding factors, including other therapeutic agents (P = .003). Angiotensin-receptor blockers and potassium-sparing diuretics were also associated with slower AAA growth rates, although these effects were not independent of all confounders. CONCLUSION: Diabetes or its medications, or both, have a negative effect on AAA growth. Because of polypharmacy, demonstrating the independent effects of individual drugs affecting the renin-angiotensin system was not possible. In light of this analysis, however, strong associations between angiotensin-receptor blockers and aldosterone-receptor blockers and slowed AAA progression are credible.

A sustained mortality benefit from screening for abdominal aortic aneurysm.

BACKGROUND: Longer-term mortality benefit and cost-effectiveness for abdominal aortic aneurysm (AAA) screening are uncertain. OBJECTIVE: To estimate the benefits, in terms of AAA-related and all-cause mortality, and cost-effectiveness of ultrasonography screening for AAA in a group that was invited to screening compared with a group that was not invited at a mean 7-year follow-up. DESIGN: Randomized trial. SETTING: 4 centers in the United Kingdom. PATIENTS: Population-based sample of 67,770 men age 65 to 74 years. INTERVENTION: Patients with an AAA detected at screening had surveillance and were offered surgery after predefined criteria were met. MEASUREMENTS: Mortality data were obtained after flagging on the national database. Unit costs obtained from large samples were applied to individual event data for the cost analysis. RESULTS: The hazard ratio was 0.53 (95% CI, 0.42 to 0.68) for AAA-related mortality in the group invited for screening. The rupture rate in men with normal results on initial ultrasonography has remained low: 0.54 rupture (CI, 0.25 to 1.02 ruptures) per 10 000 person-years. In terms of all-cause mortality, the observed hazard ratio was 0.96 (CI, 0.93 to 1.00). At the 7-year follow-up, cost-effectiveness was estimated at $19 500 (CI, $12,400 to $39,800) per life-year gained based on AAA-related mortality and $7600 (CI, $3300 to infinity) per life-year gained based on all-cause death. (All values are reported in U.S. dollars [U.K. 1 pound sterling = U.S. $1.58]). LIMITATION: Inclusion of deaths from aortic aneurysm at an unspecified site, which may include some thoracic aortic aneurysms, may have underestimated the treatment effect. CONCLUSIONS: These results from a large, pragmatic randomized trial show that the early mortality benefit of screening ultrasonography for AAA is maintained in the longer term and that the cost-effectiveness of screening improves over time. International Standard Randomized Controlled Trial registration number: ISRCTN37381646.

Assessment of the criteria for elective surgery in screen-detected abdominal aortic aneurysms.

OBJECTIVES: Apart from aortic diameter, two other widely used criteria for considering surgery in screen-detected abdominal aortic aneurysms (AAAs)--annual aortic expansion > or =1.0 cm and presence of symptoms attributable to the AAA--are based on accepted practice and AAA expansion rates, rather than direct evidence. The Multi-centre Aneurysm Screening Study (MASS) enables assessment of their contribution to this risk reduction. METHODS: MASS employs three criteria for referral for considering elective open surgery: maximum aortic diameter > or =5.5 cm, rapid aortic expansion (> or =1.0 cm/year), and/or the presence of symptoms attributable to the AAA. Data from MASS are used to examine the value of these criteria in practice. RESULTS: No patients were referred for symptoms alone. Of those referred for rapid expansion, 88% were returned to surveillance, compared with only 12% of those referred for diameter > or =5.5 cm at initial scan, and 34% of those referred for diameter > or =5.5 cm at a follow-up scan. Return to surveillance following referral for rapid expansion was strongly associated with aortic diameter (age-adjusted odds ratio for return 0.89 per mm, 95% confidence interval 0.79-1.00). Of those 5.0-5.4 cm at the time of referral for rapid expansion who were returned, 31% reached 5.5 cm during a median post-referral follow-up of 0.9 years. Among those referred for expansion, the rupture rate was only 8 per 1000 person-years of follow-up prior to reaching 5.5 cm. CONCLUSIONS: A single criterion for considering elective surgery is recommended in screen-detected AAA, based on a maximum aortic diameter of > or =5.5 cm. This criterion detects the majority of those at risk from rupture, and is simple to assess.

Are antihypertensive drugs associated with abdominal aortic aneurysms?

OBJECTIVE: The aim of this study was to investigate the association between anti-hypertensive drugs, the risk of developing an abdominal aortic aneurysm (AAA), aortic wall stiffness, collagen turnover, and change in aortic diameter. STUDY DESIGN, SETTINGS AND METHODS: Data on present medication, smoking status, and medical history of participants in two population-based aneurysm screening programs in the United Kingdom were collected by use of questionnaire. Aortic elasticity was measured by M-mode ultrasound scanning. A serum radioimmunoassay of the amino-terminal propeptide of type III procollagen was used to assess collagen turnover in one of the patient series. RESULTS: Data from 438 cases with an AAA >29 mm and 5373 controls were analyzed. Calcium-channel blockers were independently associated with AAA. The odds ratio of having an AAA was 2.6 (95% confidence interval [CI], 1.5-4.2) after adjusting for all relevant confounders. Other antihypertensive drugs showed no increased risk. No significant differences in growth rates were found in cases exposed to any of the main antihypertensive drugs. An increased collagen turnover was found in subjects receiving angiotensin-converting enzyme (ACE) inhibitors: 4.26 mg/L (95% CI, 3.73-4.79) compared with 3.62 mg/L (95% CI, 3.49-3.76) for subjects not receiving ACE inhibitors. No differences in type III collagen turnover was found with use of any other antihypertensive drug. The mean aortic wall stiffness was greater for all subjects exposed to calcium-channel blockers, whether with AAA or not: 25.1 arbitrary units (95% CI, 20.0-30.2) vs 19.3 (95% CI, 18.1-20.4)(P =.002). By contrast, the mean stiffness for cases receiving ACE inhibitors was smaller than for those not receiving ACE inhibitors: 19.0 (95% CI, 13.9-24.0) vs 25.2 (95% CI, 23.0-27.4). CONCLUSIONS: Calcium-channel blockers were an independent risk factor for the presence of an AAA and were associated with an increased arterial aortic wall stiffness. ACE inhibitors were associated with decreased stiffness and greater collagen turnover. No significant effects on the growth rate of small aneurysms were detected.