Statins Reduce Abdominal Aortic Aneurysm Growth, Rupture, and Perioperative Mortality: A Systematic Review and Meta-Analysis

Abstract

Background There are no recognized pharmacological treatments for abdominal aortic aneurysms ( AAA ), although statins are suggested to be beneficial. We sought to summarize the literature regarding the effects of statins on human AAA growth, rupture, and 30-day mortality. Methods and Results We conducted a systematic review and meta-analysis of randomized and observational studies using the Cochrane CENTRAL database, MEDLINE , and EMBASE up to June 15, 2018. Review, abstraction, and quality assessment were conducted by 2 independent reviewers, and a third author resolved discrepancies. Pooled mean differences and odds ratios with 95% confidence intervals were calculated using random effects models. Heterogeneity was quantified using the I² statistic, and publication bias was assessed using funnel plots. Our search yielded 911 articles. One case-control and 21 cohort studies involving 80 428 patients were included. The risk of bias was low to moderate. Statin use was associated with a mean AAA growth rate reduction of 0.82 mm/y (95% confidence interval 0.33, 1.32, P=0.001, I²=86%). Statins were also associated with a lower rupture risk (odds ratio 0.63, 95% confidence interval 0.51, 0.78, P<0.0001, I²=27%), and preoperative statin use was associated with a lower 30-day mortality following elective AAA repair (odds ratio 0.55, 95% confidence interval 0.36, 0.83, P=0.005, I²=57%). Conclusions Statin therapy may be associated with reduction in AAA progression, rupture, and lower rates of perioperative mortality following elective AAA repair. These data argue for widespread statin use in AAA patients. Clinical Trial Registration URL : www.crd.york.ac.uk . Unique identifier: CRD 42017056480.

Keywords: aneurysm; meta‐analysis; rupture; statin; systematic review.

Figure 1

PRISMA study flow diagram. PRISMA indicates Preferred Reporting Items for Systematic Reviews and Meta‐Analyses.

Figure 2

The effect of statin therapy on growth rate of abdominal aortic aneurysms. *Only difference provided. Control growth set as reference. Adjusted for baseline aneurysm diameter, aneurysm length, age, sex, weight, hypertension, diabetes mellitus, cerebrovascular disease, hyperlipidemia, and chronic kidney disease. ^†Adjusted for baseline aneurysm diameter, age, sex, diabetes mellitus, chronic obstructive pulmonary disease, claudication, nonsteroidal anti‐inflammatory drugs. ^‡Reduced control group size due to unavailability of medication information. Adjusted for baseline aneurysm diameter, age, sex, smoking, hypertension, coronary artery disease, diabetes mellitus, ankle‐brachial index, antiplatelet medications, any antihypertensives, angiotensin‐converting enzyme inhibitors, β‐blockers, calcium channel blockers. ^§Adjusted for baseline aneurysm diameter, aneurysm curvature, sex, smoking, mean arterial pressure, antihyperglycemic medications. ^||Adjusted for baseline aneurysm diameter, age, sex, smoking, diabetes mellitus, cerebrovascular disease, cholesterol, antihypertensives, aspirin. ^#Adjusted for demographics, diagnoses, smoking status, drug use and dose, and healthcare utilization among many covariates. Cited sources: Sukhija 200655; Karrowni 201144; Schlosser 200852; Schouten, van Laanen 200654; Nakayama 201450; Karlsson 200943; Sweeting 201056; Mosorin 200849; Ferguson 201040; Thompson 201057; van der Meiji 201320; Lederle 2015.46 CI indicates confidence interval; IV, inverse variance.

Figure 3

The effect of statin therapy on growth rate of ≥4‐cm abdominal aortic aneurysms. *Only difference provided. Control growth set as reference. Adjusted for baseline aneurysm diameter, aneurysm length, age, sex, weight, hypertension, diabetes mellitus, cerebrovascular disease, hyperlipidemia, and chronic kidney disease. ^†Adjusted for baseline aneurysm diameter, age, sex, diabetes mellitus, chronic obstructive pulmonary disease, claudication, nonsteroidal anti‐inflammatory drugs. ^‡Adjusted for baseline aneurysm diameter, aneurysm curvature, sex, smoking, mean arterial pressure, antihyperglycemic medications. Cited sources: Sukhija 200655; Karrowni 201144; Nakayama 201450; Karlsson 200943; Sweeting 201056; van der Meiji 201320; Lederle 2015.46 CI indicates confidence interval; IV, inverse variance.

Figure 4

The effect of statin therapy on growth rate of <4 cm abdominal aortic aneurysms. *Reduced control group size due to unavailability of medication information. Adjusted for baseline aneurysm diameter, age, sex, smoking, hypertension, coronary artery disease, diabetes mellitus, ankle‐brachial index, antiplatelet medications, any antihypertensives, angiotensin‐converting enzyme inhibitors, β‐blockers, calcium channel blockers. ^†Adjusted for baseline aneurysm diameter, age, sex, smoking, diabetes mellitus, cerebrovascular disease, cholesterol, antihypertensives, aspirin. ^‡Adjusted for demographics, diagnoses, smoking status, drug use and dose, and healthcare utilization among many covariates. Cited sources: Schlosser 200852; Schouten, van Laanen 200654; Mosorin 200849; Ferguson 201040; Thompson 2010.57 CI indicates confidence interval; IV, inverse variance.

Figure 5

Funnel plot of studies investigating the effect of statins on abdominal aortic aneurysm growth. MD indicates mean growth rate difference (mm/y) with the nonstatin control group as reference; SE(MD), standard error of the mean difference.

Figure 6

The effect of statin therapy on abdominal aortic aneurysm rupture risk. *Rupture or need for repair as composite. ^†Adjusted for age >80, sex, smoking, hypertension, diabetes mellitus, stroke, chronic kidney disease. ^‡Data for this outcome provided from correspondence with authors. ^§Age‐ and sex‐matched comparison between current and never/former statin use. Adjusted for hypertension, myocardial infarction, congestive heart failure, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, diabetes mellitus, chronic kidney disease, antiplatelet medications, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, nonsteroidal anti‐inflammatory drugs, steroids, insulin, oral antihyperglycemics, inhaled chronic obstructive pulmonary disease medications, family physician visits, marital status, gross income, smoking. Cited sources: Mosorin 200849; Gokani 201542; Nakayama 201450; Wemmelund 2014.58 CI indicates confidence interval; IV, inverse variance; SE, standard error.

Figure 7

Funnel plot of studies investigating the effect of statins on abdominal aortic aneurysm rupture. OR indicates odds ratio for rupture with nonstatin control as reference; SE(log[OR]), standard error of the log odds ratio.

Figure 8

The effect of statin therapy on 30‐day mortality following elective abdominal aortic aneurysm repair. *Outcome is composite of mortality or myocardial infarction within first of either discharge or 30 postoperative days. Adjusted for age >70, chronic obstructive pulmonary disease, revised cardiac risk index, β‐blockers, propensity for β‐blockers, and propensity for statins. ^†Adjusted for age, baseline aneurysm diameter, chronic obstructive pulmonary disease, revised cardiac risk index >2, and β‐blockers. Cited sources: McNally 201048; Kertai 200445; Schouten, Kok 200653; Nakayama 201450; Leurs 200647; O'Donnell 201851; Galinanes 201541; DeMartino 2016.39 CI indicates confidence interval; IV, inverse variance; SE, standard error.

Figure 9

The effect of statin therapy on 30‐day mortality following elective open abdominal aortic aneurysm repair. *Outcome is composite of mortality or myocardial infarction within first of either discharge or 30 postoperative days. Adjusted for age >70, chronic obstructive pulmonary disease, revised cardiac risk index, β‐blockers, propensity for β‐blockers, and propensity for statins. ^†Adjusted for age, baseline aneurysm diameter, chronic obstructive pulmonary disease, revised cardiac risk index >2, and β‐blockers. Cited sources: McNally 201048; Kertai 200445; Schouten, Kok 200653; DeMartino 201639; Galinanes 2015.41 CI indicates confidence interval; IV, inverse variance; SE, standard error.

Figure 10

The effect of statin therapy on 30‐day mortality following elective endovascular abdominal aortic aneurysm. Cited sources: McNally 201048; Leurs 200647; Galinanes 2015.41 CI indicates confidence interval; IV, inverse variance; SE, standard error.

Figure 11

Funnel plot of studies investigating the effect of statins on 30‐day mortality following elective abdominal aortic aneurysm repair. OR indicates odds ratio for 30‐day mortality with nonstatin control as reference; SE(log[OR]), standard error of the log odds ratio.