Skovbo Joachim S, Obel Lasse M, Diederichsen Axel C P, Steffensen Flemming H, Frost Lars, Lambrechtsen Jess, Busk Martin, Urbonaviciene Grazina, Egstrup Kenneth, Dahl Marie, Karon Marek, Rasmussen Lars M, Hallas Jesper, Lindholt Jes Sanddal
Elite Centre for Individualized Medicine in Arterial Disease (J.S.S., L.M.O., A.C.P.D., L.M.R., J.S.L.), Odense University Hospital, Denmark.
Departments of Cardiothoracic and Vascular Surgery (J.S.S., L.M.O., M.D., J.S.L.), Odense University Hospital, Denmark.
Circulation. 2025 Aug 12;152(6):384-396. doi: 10.1161/CIRCULATIONAHA.125.074544. Epub 2025 Jul 9.
Abdominal aortic aneurysms (AAA) present with high morbidity and mortality when they occasionally rupture. No medical therapy has successfully been proven to reduce AAA growth, though both metformin and statins have been identified as potential treatments in multiple meta-analysis. This study aimed to investigate a potential relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death.
The study population included all men with screening-detected AAAs (30-55 mm) from the 2 large, population-based, randomized screening trials; the Viborg Vascular Screening trial (inclusion, 2008-2011) and the Danish Cardiovascular Screening trial (inclusion, 2014-2018). The clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. Statin exposure was quantified by defined daily doses (DDD). The primary outcome was AAA growth rate, whereas secondary outcomes included the need for repair and a composite of repair, rupture, and all-cause death. Growth rates were calculated using linear regression. To evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, 5-year follow-up, or December 31, 2021.
A total of 998 aneurysmal men (median age, 69.5 [interquartile range (IQR), 67-72] years; median AAA diameter, 35.4 [IQR, 32-41.2] mm) were included. Statin use was significantly associated with reduced AAA growth rate; an increase of 1 DDD statin per day was associated with an adjusted change in growth rate of -0.22 mm/year [95% CI, -0.39 to -0.06]; =0.009). The 5-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a significantly reduced adjusted hazard ratio (HR) of 0.82 ([95% CI, 0.70-0.97]; 0.023), which 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, with an adjusted HR of 0.83 ([95% CI, 0.73-0.94]; =0.003) per doubling of statin dose. Findings were robust in a variety of sensitivity analyses.
High-dose statin use was associated with decreased AAA growth rates and lowered risk of undergoing repair, rupture, and death. This nonrandomized study suggests that patients with AAA could benefit from high-dose statin use, beyond only targeting associated risk factors.
腹主动脉瘤(AAA)偶尔破裂时会导致高发病率和死亡率。尽管二甲双胍和他汀类药物在多项荟萃分析中被确定为潜在治疗方法,但尚未有医学疗法被成功证明可降低AAA的生长速度。本研究旨在调查他汀类药物使用与AAA生长速度以及接受修复、破裂或死亡风险之间的潜在关系。
研究人群包括来自两项大型、基于人群的随机筛查试验中所有经筛查发现患有AAA(直径30 - 55毫米)的男性;维堡血管筛查试验(纳入时间,2008 - 2011年)和丹麦心血管筛查试验(纳入时间,2014 - 2018年)。临床数据库补充了来自丹麦全国医疗保健登记处的数据,包括处方和结局数据。他汀类药物暴露量通过限定日剂量(DDD)进行量化。主要结局是AAA生长速度,次要结局包括修复需求以及修复、破裂和全因死亡的综合情况。生长速度使用线性回归计算。为评估修复风险,对患者从纳入研究开始进行随访,直至手术、破裂、死亡、5年随访或2021年12月31日。
共纳入998名患有动脉瘤的男性(中位年龄69.5岁[四分位间距(IQR),67 - 72岁];中位AAA直径35.4毫米[IQR,32 - 41.2毫米])。他汀类药物的使用与AAA生长速度降低显著相关;每天他汀类药物DDD增加1与生长速度的调整后变化为-0.22毫米/年相关[95%置信区间(CI),-0.39至-0.06];P = 0.009)。他汀类药物剂量每增加一倍,5年调整后接受修复的风险比呈现出显著降低的调整后风险比(HR)为0.82([95% CI,0.70 - 0.97];P = 0.023),在2.5年后具有统计学意义。他汀类药物的使用与综合结局(手术、破裂和死亡)的风险显著降低呈剂量依赖性,他汀类药物剂量每增加一倍,调整后HR为0.83([95% CI_{,}0.73 - 0.94];P = 0.003)。在各种敏感性分析中,研究结果均很稳健。
高剂量他汀类药物的使用与AAA生长速度降低以及接受修复、破裂和死亡的风险降低相关。这项非随机研究表明,AAA患者可能会从高剂量他汀类药物的使用中获益,而不仅仅是针对相关风险因素。