Description of the condition
Abdominal aortic aneurysm (AAA) is an abnormal dilatation of the aorta as it passes below the aortic hiatus of the diaphragm to the point of bifurcation, where it forms the left and right common iliac arteries. The clinical definition of AAA varies, although a maximum infrarenal measurement (a measurement taken below the renal artery branches) of ≥ 30 mm is commonly used (Wanhainen 2008). The prevalence of AAA is six times greater in men than in women (Pleumeekers 1995), with one study demonstrating a prevalence of 1.3% in women and 7.6% in men (Scott 2002). Apart from male gender, other risk factors for AAA include smoking, increased age, and family history of AAA (Blanchard 2000). Conclusive evidence from several studies has shown smoking to be associated with AAA (Badger 2009; Greenhalgh 2008; Wilmink 1999). One study (Wilmink 1999) estimated that the risk of AAA is seven-fold in smokers and three-fold in ex-smokers, compared with age-matched nonsmokers, and another study reported that 90% of participants with AAA were smokers (Greenhalgh 2008). Increased age has also been consistently shown as a significant risk factor (Lloyd 2010; Singh 2001). One population-based study of 6386 men and women reported no AAA in participants younger than 48 years of age, but from this age onward, the prevalence increased linearly in both men and women (Singh 2001). Family history is another known risk factor for AAA. One study reported that 9% to 12% of first-degree relatives of a participant with an AAA will develop an aneurysm (van Vlijmen-van Keulen 2002).
The decision to operate on an AAA is made when the risk of rupture is greater than the risk associated with the repair. In general, the American Heart Association and the UK Aneurysm Screening Programme recommend that patients with infrarenal AAAs measuring ≥ 55 mm should undergo repair to eliminate the risk of rupture (Hirsch 2005). Abdominal aortic aneurysms can be repaired using an open or endovascular approach. Open repair with graft placement is a major procedure and may be preferred when patients are fit because complications are fewer and patients do not routinely require follow-up. Endograft repair involving stent placement (EVAR) is considered when the patient is a high surgical risk or has coexisting medical conditions. The major risks in repairing an AAA are perioperative cardiac events, infection, and death. The 30-day mortality has been estimated at 5% in elective open surgical AAA repair compared with 1.7% with EVAR (Greenhalgh 2004; Prinssen 2004). However, a recent study showed no significant difference in survival at five years in participants who had undergone open repair compared with EVAR (Brown 2011). Patients with an infrarenal AAA of 30 mm to 54 mm are monitored by ultrasound or computed tomography (CT) scans every 3, 6, or 12 months for detection of possible expansion and the need for repair. These patients are considered for statin therapy to reduce vascular risk, decrease the risk of rupture, and reduce aneurysm growth rates (Davis 2008). Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers have also been proposed to reduce aneurysmal growth (Hackam 2006).
Recent studies have shown that even after successful surgical repair of an abdominal aortic aneurysm, participants had a poorer survival rate than healthy controls (Batt 1999; Hallett 1993; Galland 1998). Hallett (Hallett 1993) conducted a population-based study and reported a five-year survival of only 60% after repair of AAAs greater than 5 cm in diameter compared with the expected survival of 77% of age- and sex-matched controls, with most late deaths due to cardiovascular causes. In a French study (Batt 1999), five-year survival after aneurysm repair was 72% compared with 90% in the same age- and sex-matched population. Similarly, a study in England (Galland 1998) showed that the five-year survival of participants undergoing surveillance with AAAs < 4 cm and 4 cm to 5.5 cm in diameter was 62% and 45%, respectively, compared with 80% in an age- and sex-matched population. Again, a majority of late deaths were the result of cardiovascular events. Thus it would appear that even once the aneurysm is repaired, people are still at risk for experiencing cardiovascular events due to underlying atheroma and vascular risk factors.
A recent study conducted in Australia demonstrated an association between AAA thrombus volume and subsequent cardiovascular events ( Parr 2011). AAA thrombus products are also released into the circulation, where they have the potential to stimulate leukocytes and other changes that might promote atherosclerotic plaque activation and acute coronary and cerebrovascular events (Morange 2006; Parry 2009; Smith 2005; Takagi 2009).
AAA size and growth have been found to be associated with local generation of inflammation markers such as interleukin-6 (Schouten 2006). Inflammation also seems to be important in perioperative adverse cardiac events. Larger AAA size is independently associated with an increased incidence of perioperative cardiovascular complications after elective infrarenal AAA repair (Schouten 2006).
Description of the intervention
Pharmacological therapy to reduce cardiovascular risk factors such as hypertension and hypercholesterolaemia.
How the intervention might work
As people with AAA have increased cardiovascular risks, pharmacological therapy may reduce cardiovascular mortality and nonfatal cardiovascular events.
Why it is important to do this review
Two Cochrane systematic reviews on the effectiveness of surgical treatment of AAA have been conducted. Dillon 2007 compared endovascular versus open surgical repair, and Filardo 2012 examined immediate repair versus routine ultrasound surveillance. A third recently published review (Rughani 2012) examines the effectiveness of medical treatments in terms of the expansion rate of small abdominal aortic aneurysms. However, these reviews have focused on treatment of AAA rather than on treatment of vascular risk factors associated with cardiovascular mortality in participants with AAA.
Acquired risk factors such as hypertension and hypercholesterolaemia are often reversible through pharmacological therapy. Given the high mortality rate associated with these largely preventable conditions, it is important to determine which prophylaxis is most effective in preventing cardiovascular death in people with AAA. To date, no systematic review has been conducted to study the effectiveness of medical treatments in reducing CV mortality in people with AAA. This review will provide evidence on the most effective medical treatment for this important problem.