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National Adherence to Medical Management of Aortic Aneurysms

      Abstract

      Objectives

      The purpose of this study was to describe levels of adherence to guideline-based medical management in patients with aortic aneurysms, using an analogous population with coronary artery disease as a comparator. Adherence among those with aortic aneurysms has never been studied.

      Methods

      Adult patients with an aortic aneurysm or coronary artery disease diagnosed between 2004 and 2018 in the Optum Clinformatics deidentified Datamart were queried. Aneurysms were subclassified as thoracic, abdominal, or both. Receipt of an antihypertensive or antihyperlipidemic was determined through pharmacy claims. Adherence was determined as receipt of the indicated pharmacologic(s) after a diagnosis of aneurysm or coronary artery disease. Adherence was compared between those with aneurysms and coronary disease using univariable logistic regression.

      Results

      After exclusions, 194,144 patients with an aortic aneurysm and 3,946,782 with coronary artery disease were identified. Overall adherence was low (45.0%) and differed significantly by aneurysm subtype: highest in isolated thoracic (45.9%) and lowest in isolated abdominal aneurysms (42.6%). Adherence levels declined significantly after 1 year by about 15% in each aneurysm subtype. All subtypes of aneurysm had a significantly lower odds of adherence compared to those with coronary disease with odds ranging from 0.61 in those with isolated abdominal aneurysms to 0.80 with isolated thoracic aneurysms.

      Conclusions

      Adherence among those with aortic aneurysms is very low, differs by subtype, and declines with time. Levels of adherence in those with aortic aneurysms is significantly lower compared to those with coronary artery disease. This should prove a reasonable target for implementation initiatives.

      Graphical Abstract

      Keywords

      Clinical Significance
      • Adherence to medical management is low in patients with aortic aneurysms.
      • Rate of adherence differs by location of aortic aneurysm and coexisting risk factors.
      • Despite similarities, adherence is significantly higher among those with coronary artery disease.
      • Over time there has been negligeable change in rates of adherence in patients with aortic aneurysms.

      Introduction

      Cardiovascular disease accounts for approximately 800,000 deaths in the United States each year (1 in 3) and is projected to incur an annual cost of $800 billion by 2030.
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      Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.
      Risk modification for patients with coronary artery disease has been a priority for preventative cardiology for decades. Aortic disease has received less attention, though has a prevalence of approximately 5%-7% and causes around 5 in 100,000 deaths.
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      The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial.
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      Incidence and prevalence of thoracic aortic aneurysms: a systematic review and meta-analysis of population-based studies.

      Centers for Disease Control and Prevention, National Center for Health Statistics. CDC WONDER Online Database. Available at: https://wonder.cdc.gov/. Accessed November 3, 2022.

      Many types of aortic and coronary artery diseases are pathophysiologically and epidemiologically associated; as such, the medical management of aortic disease is aligned with that of coronary artery disease. Guidelines for both support blood pressure and cholesterol control.
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      2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.
      The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC)
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      The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.
      The level of adherence to aspects of these guidelines has been studied among those with coronary artery disease but has never been studied among those with aortic aneuryms.
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      Medication adherence in cardiovascular disease.
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      The magnitude of the gap between the evidentiary base and clinical practice with regard to the management of patients with aortic aneurysms is unknown.
      The current study aimed to determine the level of adherence of patients with aortic aneurysms to medical guidelines for control of hypertension and hyperlipidemia. A secondary aim was to compare levels of adherence between those with aortic aneurysms and coronary artery disease, where the latter serves as a gold standard.

      Methods

      Data Source

      The Optum Clinformatics Datamart (OptumInsight) contains deidentified administrative claims data from patients in the United States insured by a large commercial health insurer and Medicare Advantage (C and D). Geographically representative data on inpatient, outpatient, and pharmaceutical claims is available for 63 million unique patients and updated regularly.

      Cohort Identification

      We retrospectively studied all adults within Optum with a diagnosis of aortic aneurysm or coronary artery disease between 2004 and 2018. Those with aneurysms were further categorized as having an isolated thoracic, isolated abdominal, or thoracoabdominal aneurysms. Those younger than 18 years, with fewer than 6 months of continuous coverage after diagnosis, prior cardiovascular interventions, nonaneurysmal aortic disease, or lacking complete data were excluded. International Classification of Diseases diagnosis codes from versions 9 and 10 were used to identify the presence of aortic and coronary artery disease, as well as coexisting conditions (Supplementary Table 2, available online). The Elixhauser Comorbidity Index was used to categorize comorbidities other than the cardiovascular risk factors of interest. Current procedural terminology codes were used to identify procedures. Individual codes used to specify key variables are provided in Supplementary Table 1, available online.

      Risk Factor Specification

      Risk factors of interest were hypertension and hyperlipidemia. Only patients with a code present during the 6 months prior and 3 months after a diagnosis of an aortic aneurysm or coronary artery disease were considered to have an active diagnosis. Patients were given this forward-facing window to allow sufficient screening time in cases where insurance coverage coincided with date of aortic or coronary artery disease diagnosis (Supplementary Figure 1, available online).

      Determination of Treatment and Adherence

      Receipt of an antihypertensive or antihyperlipidemic was determined by the presence of a pharmacy claim. Individual pharmaceutics were queried using codes from the National Drug Code Directory. The suitability of each pharmaceutic for the treatment of hypertension or hyperlipidemia in the setting of aortic or coronary artery disease was made in alignment with joint guidelines from the American Heart Association and American Association for Thoracic Surgery.
      • Fihn SD
      • Gardin JM
      • Abrams J
      • et al.
      2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease.
      ,
      • Hiratzka LF
      • Bakris GL
      • Beckman JA
      • et al.
      2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.
      Initial adherence was determined by the presence of a pharmacy claim anytime during the 6 months following a diagnosis of aortic or coronary artery disease (Supplementary Figure 1, available online). The level of initial adherence was calculated for hypertension, hyperlipidemia, and combined hypertension and hyperlipidemia by dividing the number of patients with at least 1 pharmacy claim to treat the risk factor(s) present by the total number with the risk factor(s). For example, if 100 patients with a thoracic aortic aneurysm carried a diagnosis of hypertension and 50 had a pharmacy claim for metoprolol in the 6 months following this diagnosis, the adherence level for hypertension among those with thoracic aneurysms would be 50%. For those with combined hypertension and hyperlipidemia, adherence was achieved only when a claim was made for both an antihypertensive and an antihyperlipidemic. Composite adherence within a diagnosis group is defined as the proportion of all patients within that group with a pharmacy claim for all of the risk factors present (ie, a weighted average of each factor-specific adherence).
      There are certain patients with aortic or coronary artery disease who do not have coexisting hypertension or hyperlipidemia for whom guidelines recommend pharmacologic treatment. Level of adherence among these patients was calculated as the proportion of patients with at least 1 pharmacy claim for the appropriate class of pharmacologic divided by the total number of patients in that group.
      In addition to initial adherence, adherence at 1 year following the diagnosis of an aortic aneurysm or coronary artery disease was evaluated. In this analysis, the presence of a claim 45 days before or after the 1-year anniversary of the diagnosis was counted as adherence. A sensitivity analysis was performed using 60- and 90-day calipers instead of a 45-day caliper.

      Outcomes

      The primary outcome was composite initial adherence to treatment of hypertension or hyperlipidemia in patients with an aortic aneurysm. A secondary outcome was initial adherence for each risk factor or combinations thereof in patients with an aneurysm. Adherence among those without risk factors was also explored. Lastly, the primary and secondary outcomes in patients with aortic aneurysms were compared to patients with coronary artery disease to define a potential gap to be addressed by implementation initiatives.

      Statistical Analysis

      The characteristics of patients with an aortic aneurysm or coronary artery disease were tabulated and described using standard descriptive statistics. Differences in adherence level between subcategories of aneurysmal disease were compared using a χ2 test. Pairwise comparisons were performed using the Bonferroni Correction. A univariable linear regression was used to analyze trends in the levels of adherence over time. Univariable logistic regression was used to compare adherence between those with aortic aneurysm and coronary artery disease, and presented as a forest plot. Data management was performed using SAS version 9.4 (SAS Institute Inc) and statistical analyses were performed using R (version 4.0.3, R Foundation). This project was deemed exempt from approval by institutional review board at the University of Pennsylvania.

      Results

      Population

      After exclusions, there were 194,144 patients with an aortic aneurysm of whom 69,028 had an isolated thoracic aortic aneurysm, 122,922 had an isolated abdominal aortic aneurysm, and 2,194 had a thoracoabdominal aneurysm. There were 3,946,782 patients with coronary artery disease (Supplementary Figure 2, available online). Among those with an aortic aneurysm, isolated hypertension (23.6%) and combined hypertension and hyperlipidemia (44.5%) were the most prevalent risk factors (Table). No primary risk factor was present in 19.5% of patients. The majority were white (68.3%) and male (61.1%) with an average age of 68.0 ± 13.0 years. All regions of the country were represented.
      TableBaseline Characteristics of the Sample Population
      CharacteristicAortic AneurysmThoracic Aortic AneurysmAbdominal Aortic AneurysmThoracic and Abdominal Aortic AneurysmCoronary Artery Disease
      Number194,14469,028122,9222,1943,946,782
      Cardiovascular risk factor
       Hypertension45,784 (23.6)18,449 (26.7)26,695 (21.7)640 (29.2)708,537 (18.0)
       Hyperlipidemia24,030 (12.4)7,265 (10.5)16,578 (13.5)187 (8.5)472,926 (12.0)
       Hypertension and hyperlipidemia86,442 (44.5)295,88 (42.9)55,958 (45.5)896 (40.8)2,394,072 (60.7)
       Tobacco use27,753 (14.3)7,212 (10.4)20,298 (16.5)243 (11.1)434,930 (11.0)
       None37,888 (19.5)13,726 (19.9)23,691 (19.3)471 (21.5)371,247 (9.4)
      Demographics
       Age (mean [SD])68.0 (13.0)65.7 (14.3)69.3 (12.0)65.3 (14.9)66.7 (12.6)
       Male118,598 (61.1)41,336 (59.9)76,149 (61.9)1,113 (50.7)2,225,753 (56.4)
      Race
       White132,562 (68.3)47,790 (69.2)83,346 (67.8)1426 (65.0)2,534,945 (64.2)
       Black14,890 (7.7)5000 (7.2)9674 (7.9)216 (9.8)400,254 (10.1)
       Hispanic12,736 (6.6)3988 (5.8)8579 (7.0)169 (7.7)339,668 (8.6)
       Asian5246 (2.7)1966 (2.8)3223 (2.6)57 (2.6)90,286 (2.3)
      Education
       Did not graduate high school929 (0.5)232 (0.3)684 (0.6)13 (0.6)26,526 (0.7)
       High school graduate48,593 (25.0)14,949 (21.7)33,093 (26.9)551 (25.1)1,212,184 (30.7)
       Bachelor's degree94,169 (48.5)33,528 (48.6)59,571 (48.5)1070 (48.8)1,790,596 (45.4)
       Advanced degree27,141 (14.0)12,110 (17.5)14,740 (12.0)291 (13.3)440,199 (11.2)
       Unknown23,312 (12.0)8209 (11.9)14,834 (12.1)269 (12.3)477,277 (12.1)
      Income
       <$40,00036,705 (18.9)11,450 (16.6)24,857 (20.2)398 (18.1)839,682 (21.3)
       $40,000-$49,00011,122 (5.7)3615 (5.2)7407 (6.0)100 (4.6)226,743 (5.7)
       $50,000-$59,00011,822 (6.1)3947 (5.7)7754 (6.3)121 (5.5)233,962 (5.9)
       $60,000-$74,00016,035 (8.3)5559 (8.1)10,325 (8.4)151 (6.9)305,679 (7.7)
       $75,000-$99,00022,267 (11.5)8356 (12.1)13,693 (11.1)218 (9.9)396,690 (10.1)
       >$100,00038,378 (19.8)17,153 (24.8)20,818 (16.9)407 (18.6)625,022 (15.8)
       Unknown57,815 (29.8)18,948 (27.4)38,068 (31.0)799 (36.4)1,319,004 (33.4)
      Division
       New England10,644 (5.5)4,283 (6.2)6,237 (5.1)124 (5.7)166,398 (4.2)
       Middle Atlantic21,072 (10.9)6,948 (10.1)13,963 (11.4)161 (7.3)365,434 (9.3)
       East North Central27,161 (14.0)11,009 (15.9)15,824 (12.9)328 (14.9)538,323 (13.6)
       West North Central19,004 (9.8)7751 (11.2)11,013 (9.0)240 (10.9)329,661 (8.4)
       South Atlantic45,032 (23.2)14,549 (21.1)29,994 (24.4)489 (22.3)1,072,338 (27.2)
       East South Central7165 (3.7)2440 (3.5)4621 (3.8)104 (4.7)198,979 (5.0)
       West South Central19,099 (9.8)6442 (9.3)12,400 (10.1)257 (11.7)540,872 (13.7)
       Mountain18,239 (9.4)6465 (9.4)11,608 (9.4)166 (7.6)304,340 (7.7)
       Pacific25,718 (13.2)8827 (12.8)16,572 (13.5)319 (14.5)413,109 (10.5)
       Unknown1010 (0.5)314 (0.5)690 (0.6)6 (0.3)17,328 (0.4)
      Elixhauser comorbidities
       Congestive heart failure12,658 (6.5)5792 (8.4)6683 (5.4)183 (8.3)594,803 (15.1)
       Valvular disease33,349 (17.2)21,196 (30.7)11,714 (9.5)439 (20.0)585,319 (14.8)
       Pulmonary circulation disease5691 (2.9)2944 (4.3)2660 (2.2)87 (4.0)122,189 (3.1)
       Peripheral vascular disease185,455 (95.5)66,782 (96.7)116,561 (94.8)2112 (96.3)510,271 (12.9)
       Hypertension119,530 (61.6)43,093 (62.4)75,065 (61.1)1372 (62.5)2,702,872 (68.5)
       Paralysis3310 (1.7)1272 (1.8)1997 (1.6)41 (1.9)79,342 (2.0)
       Other neurological disorders17,796 (9.2)6916 (10.0)10,643 (8.7)237 (10.8)366,476 (9.3)
       Chronic pulmonary disease46,431 (23.9)16,047 (23.2)29,859 (24.3)525 (23.9)801,865 (20.3)
       Diabetes mellitus28,498 (14.7)8402 (12.2)19,845 (16.1)251 (11.4)912,788 (23.1)
        without chronic complications15,755 (8.1)4483 (6.5)11,127 (9.1)145 (6.6)448,509 (11.4)
        with chronic complications13,041 (6.7)4008 (5.8)8925 (7.3)108 (4.9)473,637 (12.0)
       Hypothyroidism16,721 (8.6)6242 (9.0)10,261 (8.3)218 (9.9)320,359 (8.1)
       Renal failure18,246 (9.4)6057 (8.8)11,990 (9.8)199 (9.1)397,847 (10.1)
       Liver disease9974 (5.1)3597 (5.2)6276 (5.1)101 (4.6)128,016 (3.2)
       Peptic ulcer disease with bleeding1109 (0.6)410 (0.6)691 (0.6)8 (0.4)20,239 (0.5)
       AIDS112 (0.1)47 (0.1)64 (0.1)1 (0.0)2085 (0.1)
       Lymphoma1757 (0.9)807 (1.2)935 (0.8)15 (0.7)23,639 (0.6)
       Metastatic cancer4868 (2.5)1907 (2.8)2900 (2.4)61 (2.8)51,785 (1.3)
       Solid tumor without metastasis9344 (4.8)3451 (5.0)5806 (4.7)87 (4.0)123,132 (3.1)
       Rheumatoid arthritis9169 (4.7)3428 (5.0)5621 (4.6)120 (5.5)173,010 (4.4)
       Coagulopathy6369 (3.3)2550 (3.7)3733 (3.0)86 (3.9)113,769 (2.9)
       Obesity17,409 (9.0)7682 (11.1)9543 (7.8)184 (8.4)472,220 (12.0)
       Weight loss11,080 (5.7)3715 (5.4)7254 (5.9)111 (5.1)134,948 (3.4)
       Fluid and electrolyte disorders22,085 (11.4)8323 (12.1)13,441 (10.9)321 (14.6)466,429 (11.8)
       Chronic blood loss anemia2119 (1.1)703 (1.0)1379 (1.1)37 (1.7)40,931 (1.0)
       Vitamin deficiency anemias25,336 (13.1)8260 (12.0)16,772 (13.6)304 (13.9)530,938 (13.5)
       Alcohol abuse3866 (2.0)1421 (2.1)2403 (2.0)42 (1.9)63,949 (1.6)
       Drug abuse2384 (1.2)889 (1.3)1464 (1.2)31 (1.4)52,428 (1.3)
       Psychoses8003 (4.1)2940 (4.3)4953 (4.0)110 (5.0)177,489 (4.5)
       Depression17,046 (8.8)6693 (9.7)10,168 (8.3)185 (8.4)380,545 (9.6)
      AIDS = acquired immunodeficiency syndrome; SD = standard deviation.
      All values are in number (%) format unless otherwise specified.
      Supplementary Table 1Pharmacologic Agents Considered Appropriate Treatment for Risk Factors of Interest
      Risk factorPharmacologic treatment
      Hypertension
      Combination therapeutics included but not listed.
      amlodipine, benazepril, captopril, enalapril, fosinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, lisinopril, candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, acebutolol, atenolol, betaxolol, bisoprolol, metoprolol, nebivolol, carvedilol, labetalol, nadolol, pindolol, propranolol, sotalol, timolol, nifedipine, clonidine
      Hyperlipidemia
      Combination therapeutics included but not listed.
      atorvastatin, simvastatin, rosuvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, ezetimibe, colestipol hydrochloride, gemfibrozil, fenofibric acid, niacin
      Tobacco use
      Referral to smoking cessation counseling (CPT codes 99406 and 99407) also considered treatment, though not pharmacologic.
      varenicline tartrate, bupropion, nicotine replacement therapy
      low asterisk Combination therapeutics included but not listed.
      Referral to smoking cessation counseling (CPT codes 99406 and 99407) also considered treatment, though not pharmacologic.
      Supplementary Table 2ICD-10-CM, ICD-9-CM, and CPT Codes Used to Specify Key Study Variables
      EntityICD-10-CM codeICD-9-CM codeCPT
      Aortic diseaseI71.1, I71.3, I71.5, I71.8, I71.2, I71.4, I71.6, I71.9, I71.0, I71.01, I71.02, I71.03441.1, 441.5, 441.3, 441.6, 441.5, 441.2, 441.4, 441.7, 441.9, 441.0, 441.00, 441.01, 441.02, 441.03
      Coronary artery diseaseI25.10, I25.1, I25.11, I25.4, I25.41, I25.42, I25.9, I21.18, I25.119, I25.2, I25.5, I25.6, I25.8, I25.9, I24.0, I24.1, I24.8, I24.9, I20.0, I20.1, I20.8, I20.9414.00, 414, 414.0, 414.9, 414.8, 414.01, 414.2, 414.3, 414.4
      HypertensionI10.x, I11.x-I13.x, I15.x401.1, 401.9, 402.10, 402.90, 404.10, 404.90, 405.1, 405.9
      HyperlipidemiaE780,E780.0,E780.1,E781,E782,E783,E784,E784.1,E784.9,E785,E789272.0,272.1,.272.2,272.3,272.4
      Tobacco useF17.20, F17.200, F17.201, F17.208, F17.209, F17.21, F17.210, F17.211, F17.218, F17.219, F17.22, F17.220, F17.223, F17.228, F17.229, F17.29, F17.290, F17.291, F17.293, F17.298, F17.299(does not include “history of” tobacco use, which is Z87.891, tobacco use NOS)305.1
      Aortic procedures33858,33859, 33863, 33864, 33866, 33871, 33875, 33877, 34830, 34831, 34832, 34833, 34834, 33880, 33881, 33883, 33884, 33886, 33889, 33891, 34701, 34702, 34703, 34704, 34705, 34706, 34707, 34708, 34710, 34712, 34839, 34841, 34842, 34843, 34844, 34845, 34846, 34847, 34848
      Cardiac procedures33510, 33511, 33512, 33513, 33514, 33516, 33517, 33518, 33519, 33521, 33522, 33523, 33533, 33534, 33535, 33536, 92920, 92924, 92928, 92933, 92937, 92941, 92943
      There was a significant increase in the number of patients diagnosed with aortic aneurysms from 5,514 in 2004 to 28,308 in 2018, with increases in all 3 aneurysm subtypes (P < .001) (Figure 1). The rate of annual increase appears similar for those with and without risk factors (Supplementary Figure 3, available online)
      Figure 1
      Figure 1Number of patients diagnosed with an aortic aneurysm between 2004 and 2018, stratified by region of disease.

      Initial Adherence Among Those with an Aortic Aneurysm

      Among those with an aortic aneurysm and coexisting risk factors, isolated hypertension was treated in 56.8% of cases, isolated hyperlipidemia in 37.8%, and both hypertension and hyperlipidemia in 40.8% of cases when present concurrently. Overall adherence was 45.0% among those with a risk factor(s) and any type of aortic aneurysm.
      Levels of adherence for each risk factor(s) differed by aortic disease subtype, as did composite adherence (Figure 2A). Those with thoracic aortic disease were found to have the highest level of composite adherence (49.2%) followed by thoracoabdominal (45.9%) and abdominal aortic aneurysm (42.6%). There were significant differences in composite adherence between each aneurysm type.
      Figure 2
      Figure 2(A) Percentage of patients with a diagnosis of CAD, TAA, AAA, or thoracoabdominal aortic aneurysm (TAA and AAA) with coexisting risk factors who received pharmacologic therapy. (B) Change in composite adherence to pharmacologic therapy over time. AAA = abdominal aortic aneurysm; CAD = coronary artery disease; TAA = thoracic aortic aneurysm.
      The level of composite adherence among those with an isolated thoracic aneurysm increased by 0.18% each year (P = .013) (Figure 2B). There was no significant change overtime in levels of composite adherence for those with abdominal (0.09% per year, P = .32) or thoracoabdominal aneurysms (0.31% per year, P = .27).
      The rate of adherence among those with an aortic aneurysm but without coexisting risk factors was on average lower than for those with coexisting risk factors (26.2% vs 45.0%, P < .001). An antihypertensive was received by 29.2% of patients with an isolated thoracic aneurysm, 18.4% with abdominal, and 26.7% with a thoracoabdominal aneurysm (Figure 3A). An antihyperlipidemic was received by only 13.1% of those with an abdominal aortic aneurysm without coexisting hyperlipidemia. Receipt of an antihypertensive among those with a thoracic aneurysm (either in isolation or in combination with an abdominal aneurysm) without hypertension but was significantly higher than for those with an isolated abdominal aneurysm (29.2% vs 18.3%, P < .001). Over time, the rate of adherence among those without coexisting risk factor declined by 0.43% per year among those with an isolated thoracic aneurysm (P = .01), and slowly increased by 0.21% per year for those with an isolated aortic aneurysm (P = .01; Figure 3B). There was no significant change in the rate of adherence among those with a thoracoabdominal aneurysm (0.24% per year, P = .17).
      Figure 3
      Figure 3(A) Percentage of patients with a diagnosis of TAA, AAA, or thoracoabdominal aortic aneurysm (TAA and AAA) without coexisting risk factors who received pharmacologic therapy. (B) Change in composite adherence to pharmacologic therapy over time. AAA = abdominal aortic aneurysm; TAA = thoracic aortic aneurysm.

      Adherence After 1 Year Among Those with an Aortic Aneurysm

      Regardless of aneurysm subtype or presence of coexisting risk factors, the rate of adherence 1 year after initial diagnosis was lower than the initial rate of adherence. Among those with coexisting risk factors, a 16.3% decline was observed in those with isolated thoracic aortic aneurysms (P < .001), 11.2% with abdominal (P < .001), and 14.9% with thoracoabdominal aneurysms (P < .001; Figure 4A). Among those without coexisting risk factors, patients with isolated thoracic aortic aneurysms experienced a decline of 11.0% (P < .001), whereas those with abdominal (2.3%, P < .001) or thoracoabdominal aneurysms (1.2%, P = .47) experienced much smaller declines (Figure 4B). A sensitivity analysis wherein a 60- and 90-day caliper was used instead of a 45-day caliper to capture adherence at 1 year showed that widening the caliper was associated with small increases in adherence within each diagnosis group (Supplementary Figure 4, available online).
      Figure 4
      Figure 4Rates of pharmacotherapy after initial diagnosis of TAA, AAA, or thoracoabdominal aortic aneurysm (TAA and AAA) and at 1 year following the diagnosis among patients with (A) and without (B) coexisting risk factors. AAA = abdominal aortic aneurysm; TAA = thoracic aortic aneurysm.

      Comparison of Adherence Between Patients with Aortic Aneurysms and Coronary Artery Disease

      Composite adherence among those with coronary artery disease was 54.3%, and significantly higher than for patients with any type of aortic aneurysm and coexisting risk factors (P < .05 for each) (Figure 2A). In patients without risk factors, an antihyperlipidemic was received by 27.5% of patients with coronary artery disease (Figure 3A).
      Among aneurysm subtypes, those with an abdominal aortic aneurysm experienced the lowest overall odds of receiving the appropriate pharmacologic compared to those with coronary artery disease, regardless of coexisting risk factor(s) (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.60 to 0.62, P < .001) (Figure 5). In particular, those with hyperlipidemia fared the worst (OR 0.52, 95% CI 0.50 to 0.54, P < .001). In contrast, those with an isolated thoracic aneurysm experience the highest overall odds of receiving the appropriate pharmacologic therapy for each risk factor alone (OR 0.8, 95% CI 0.79 to 0.82, P < .001; Figure 5). Those with an isolated thoracic aneurysm had nonsignificantly higher odds of receipt of pharmacotherapy compared to those with coronary artery disease and hypertension (OR 1.02, 95% CI 0.99 to 1.05, P = .20).
      Figure 5
      Figure 5Forest plot showing the odds of adherence among those with a diagnosis of TAA, AAA, or thoracoabdominal aortic aneurysm (TAA and AAA) with coexisting risk factors compared to those with CAD (reference). AAA = abdominal aortic aneurysm; CAD = coronary artery disease; TAA = thoracic aortic aneurysm.
      Supplementary Figure 1
      Supplementary Figure 1Schematic of study design illustrating relationship among windows for risk factor diagnosis, treatment, and continuous enrollment.
      Supplementary Figure 2
      Supplementary Figure 2Flow diagram illustrating specification of study samples for patients with aortic disease and coronary artery disease.
      Supplementary Figure 3
      Supplementary Figure 3Bar chart illustrating the number of patients diagnosed with an aortic aneurysm at least 1 primary risk factor (A) or without any of the primary risk factors (B) between 2004 and 2018, stratified by region of disease.
      Supplementary Figure 4
      Supplementary Figure 4Sensitivity analysis of 60-day (A) and 90-day (B) calipers to capture adherence around the 1-year anniversary of the diagnosis of a TAA, AAA, or thoracoabdominal aortic aneurysm (TAA and AAA). The same analysis was done for those with coexisting risk factors. A similar analysis was done of 60-day (C) and 90-day (D) calipers among those without coexisting risk factors. AAA = abdominal aortic aneurysm; TAA = thoracic aortic aneurysm.

      Discussion

      In this study we used pharmaceutical claims to measure levels of adherence to guideline-based medical management in a large sample of patients with aortic aneurysms, using an analogous population with coronary artery disease as a comparator. We found that adherence among those with an aortic aneurysm and hypertension or hyperlipidemia is low (∼45.0%), ranging from approximately 43% in those with an isolated abdominal aneurysm to 49% in those with an isolated thoracic aneurysms, and that these levels have not meaningfully improved over time. Additionally, after a period of 1 year, adherence levels declined by roughly 15%. Lower adherence was seen among those without risk factors compared to those with risk factors. Lastly, we identified a significant gap between adherence in those with aortic aneurysms compared to coronary artery disease (∼10%), which should prove a reasonable target for implementation initiatives.
      The aim of medical therapy in those with aortic aneurysms is 2-fold: to decrease nonaortic morbidity and mortality attendant to the high prevalence of comorbidities in this population and reduce aortic-specific mortality and morbidity through slowing of aortic enlargement, prevention of rupture, and avoidance of intervention. Control of hypertension accomplishes this through reduction of shear stress, in which limiting spikes in blood pressure and reducing the frequency of impulses from cardiac contraction are particularly important. Atherosclerotic aneurysms are a risk factor equivalent for coronary artery disease, and control of hyperlipidemia is primarily aimed at reduction of cardiac and cerebrovascular complications. That said, statins have been associated with inhibition of aneurysm expansion in small observational studies and may be directly beneficial to aortic health.
      Among those with thoracic aortic aneurysms, there is a Class 1 recommendation for pharmacologic treatment of hypertension and hyperlipidemia.
      • Hiratzka LF
      • Bakris GL
      • Beckman JA
      • et al.
      2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.
      Among those without hypertension there is a Class 2 recommendation for blood pressure reduction.
      • Hiratzka LF
      • Bakris GL
      • Beckman JA
      • et al.
      2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.
      Guidelines for the medical management of abdominal aneurysms are less well-developed. For those with abdominal aortic aneurysms there are Class 2 recommendations for use an antihypertensive (specifically angiotensin-converting enzyme inhibitors) and statins in patients with hypertension and hyperlipidemia, respectively, as well as in those without.
      The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC)
      2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult.
      Guidelines for coronary artery disease are more well developed, and provide a Class I recommendation for the pharmacologic treatment of hypertension and hyperlipidemia.
      • Fihn SD
      • Gardin JM
      • Abrams J
      • et al.
      2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease.
      Additionally strong recommendations are provided for use of statins in those without elevated cholesterol.
      • Braun MM
      • Stevens WA
      • Barstow CH.
      Stable coronary artery disease: treatment.
      ,
      Task Force on the management of stable coronary artery disease of the European Society of Cardiology
      2013 ESC guidelines on the management of stable coronary artery disease. The Task Force on the management of stable coronary artery disease of the European Society of Cardiology.
      To our knowledge, there have been no prior analyses of levels of adherence to guideline-based medical management among patients with an aortic aneurysm. Among those with coronary artery disease, most studies report adherence levels in the range of 50%-70%.
      • Baroletti S
      • Dell'Orfano H
      Medication adherence in cardiovascular disease.
      ,
      • Jackevicius CA
      • Mamdani M
      • Tu JV.
      Adherence with statin therapy in elderly patients with and without acute coronary syndromes.
      ,
      • Khatib R
      • Marshall K
      • Silcock J
      • Forrest C
      • Hall AS.
      Adherence to coronary artery disease secondary prevention medicines: exploring modifiable barriers.
      ,
      • Kolandaivelu K
      • Leiden BB
      • O'Gara PT
      • Bhatt DL.
      Non-adherence to cardiovascular medications.
      Even following acute myocardial infarction, adherence practices captured in high-quality registries show that only 66% (PREMIER registry) and 78% of patients (EFFECT registry) fill key prescriptions within 120 days.
      • Ho PM
      • Spertus JA
      • Masoudi FA
      • et al.
      Impact of medication therapy discontinuation on mortality after myocardial infarction.
      ,
      • Jackevicius CA
      • Li P
      • Tu JV.
      Prevalence, predictors, and outcomes of primary nonadherence after acute myocardial infarction.
      Rates of adherence level between 52.2% and 62.1% reported in this study for all comers with coronary artery disease—and not only those with recent acute myocardial infarction—are consistent with other samples. This lends credibility to rates of adherence observed among those with aortic aneurysm.
      That patients with aortic aneurysms and coronary artery disease share common guidelines for control of these prominent cardiovascular risk factors is intuitive. Less so is why a significant gap in adherence should exist between them. Potential explanations include more intense academic and public focus on coronary artery disease due to higher prevalence, existence of professional and societal organizations around cardiac disease, and a higher level of urgency attributed by patients to cardiac conditions than to aortic ones. With this, guidelines for management of coronary artery disease are more well supported, which in turn may drive better adherence. It is our hope that identification of this gap galvanizes implementation actions that may bring adherence among those with aneurysms into parity with coronary artery disease.

      Limitations

      This study has several important limitations. First, our sample is composed of insured patients who are mostly privately insured. This is likely to bias adherence upward compared to the general population. Further, we were reliant on claims data, which is subject to coding error and may not capture important characteristics. Furthermore, increases in the frequency of diagnoses or pharmacy claims in insurance claims data may not reflect true changes in the incidence of a disease or prescribing habit but may reflect changes in coding due to electronic health records and or evolving coding systems (eg, switch from International Classification of Diseases diagnosis code version 9 to 10). Additionally, adherence to the full breadth of guideline-directed pharmacotherapy could not be accurately analyzed because some recommended therapies do not require a prescription and therefore would not generate a claim. An important example is smoking cessation, which is recommended for patients with aortic aneurysms or coronary artery disease but for whom nicotine replacement therapy would not be adequately captured. Another example is aspirin. Lastly, we were not able to track patient blood pressure or cholesterol levels to inform our definition of compliance.

      Conclusion

      In conclusion, adherence among those with aortic aneurysms is very low, differs by subtype, and declines with time. Levels of adherence in those with aortic aneurysms is significantly lower compared to those with coronary artery disease. This gap represents a reasonable target for improvement through awareness and implementation initiatives.

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