A five-year prospective cohort study—using longitudinal registry data from two population-based screening trials—has found that high-dose statin use was associated with decreased abdominal aortic aneurysm (AAA) growth rates and lowered risk of undergoing repair, rupture, and death. Researchers therefore suggest high-dose statins should be “strongly considered” for patients with small AAAs.
Writing in Circulation, authors Joachim S Skovbo (Odense University Hospital, Odense, Denmark) and colleagues state that AAAs present with high morbidity and mortality when they occasionally rupture. Multiple meta-analyses have identified both metformin and statins as potential treatments, the authors go on to note, but neither has successfully been proven to reduce AAA growth. The present study, therefore, aimed to investigate a relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death.
Skovbo and colleagues detail that the study population included all men with screening-detected AAAs—ranging in diameter from 30–55mm—from two large, population-based screening trials: the Viborg Vascular Screening trial and the Danish Cardiovascular Screening trial, which included patients in the years 2008–2011 and 2014–2018, respectively. The authors add that the clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. In order to evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, five-year follow-up, or 31 December 2021.
The researchers included a total of 998 aneurysmal men with a mean age of 69.5 years and a median AAA diameter of 35.4mm in the study. They report in Circulation that statin use was “significantly associated with reduced AAA growth rate,” sharing that an increase of one defined daily dose statin per day was associated with an adjusted change in growth rate of -0.22mm per year.
Additionally, Skovbo and colleagues relay that the five-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a “significantly reduced adjusted hazard ratio” of 0.82, which they note was significant after 2.5 years.
“Statin use was associated with a significantly lower risk of the composite outcome (surgery, rupture, and death) in a dose-dependent manner,” the authors continue, citing an adjusted hazard ratio of 0.83 per doubling of statin dose.
Skovbo and colleagues write that their findings were “robust” in several sensitivity analyses and conclude that high-dose statin use was associated with a dose-dependent reduction in AAA growth rates and a lower risk of undergoing repair, rupture, and death during a five-year follow-up period.
“These findings study suggest that high-dose statins may offer direct protection against AAA progression, beyond cardiovascular risk reduction alone,” Skovbo and colleagues write.
Considering the clinical implications of their work, the authors advise that, “Because of their proven cardiovascular benefits, safety profile, and cost-effectiveness, high-dose statins should be strongly considered for patients with small AAAs, particularly those without contraindications.”
“Although randomised trials may be ethically challenging,” the authors continue, “further high-quality observational studies are needed to validate these findings and inform clinical guidelines.”
Generalisability concerns
In their Circulation paper, Skovbo and colleagues highlight certain limitations that curb the generalisability of their findings. For example, they note that the study included only male patients, reducing the generalisability of the results to the female population.
Furthermore, the authors recognise that the study cohort primarily consists of White individuals from a Western society between 60 and 74 years of age, going on to note that “caution is warranted when extrapolating these findings to other racial and ethnic groups, age groups, or different societal contexts”.
Recognising the difficulties of performing randomised controlled trials to assess to treatment options for patients with AAA, the authors instead “advocate for observational studies with a similar design, emphasising precise exposure measurement and detailed dose-response outcome, to replicate and further validate our findings especially in women and ethnic groups”.
