Key result
PCSK9 inhibition shows potential to limit abdominal aortic aneurysm progression and cardiovascular events.
Why the study?
There are no current drug therapies to limit abdominal aortic aneurysm (AAA) growth, prompting a review of evidence on PCSK9 as a potential drug target.
PCSK9 inhibition emerges as a biologically plausible, promising pharmacological strategy for treating abdominal aortic aneurysms, establishing a strong rationale for future randomized controlled trials.
PURPOSE OF REVIEW: There are no current drug therapies to limit abdominal aortic aneurysm (AAA) growth. This review summarizes evidence suggesting that inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) may be a drug target to limit AAA growth. RECENT FINDINGS: Mendelian randomization studies suggest that raised LDL and non-HDL-cholesterol are causal in AAA formation. PCSK9 was reported to be upregulated in human AAA samples compared to aortic samples from organ donors. PCSK9 gain of function viral vectors promoted aortic expansion in C57BL/6 mice infused with angiotensin II. The effect of altering PCSK9 expression in the aortic perfusion elastase model was reported to be inconsistent. Mutations in the gene encoding PCSK9, which increase serum cholesterol, were associated with increased risk of human AAA. Patients with AAA also have a high risk of cardiovascular death, myocardial infarction and stroke. Recent research suggests that PCSK9 inhibition would substantially reduce the risk of these events. SUMMARY: Past research suggests that drugs that inhibit PCSK9 have potential as a novel therapy for AAA to both limit aneurysm growth and reduce risk of cardiovascular events. A large multinational randomized controlled trial is needed to test if PCSK9 inhibition limits AAA growth and cardiovascular events.
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Golledge et al. (2024) conducted a review in Abdominal aortic aneurysm. PCSK9 inhibition was evaluated. Past evidence from genetic, animal, and observational studies suggests that PCSK9 inhibition has potential as a novel therapy to limit abdominal aortic aneurysm growth and reduce cardiovascular events.
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