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Abstract
Objectives Despite guidelines endorsing statin and single antiplatelet therapy (SAPT) therapy post-carotid endarterectomy (CEA), these medications may be either under or inappropriately prescribed. We determined rates of new statin prescriptions as well as change in antiplatelet therapy (APT) regimen at discharge. We identified characteristics associated with these occurrences.
Design We performed a retrospective Vascular Quality Initiative registry analysis of more than 125 000 patients who underwent CEA from 2013 to 2021.
Setting The Vascular Quality Initiative is a multicentre registry database including academic and community-based hospitals throughout the USA.
Participants Patients age≥18 years undergoing CEA with available statin and APT data (preprocedure and postprocedure) were included.
Primary and secondary outcome measures We determined overall rates of statin and APT prescription at discharge. Multivariate logistic regression was used to determine clinical and demographic characteristics that were mostly associated with new statin prescription or changes in APT regimen at discharge.
Results Study participants were predominantly male (61%) and White (90%), with a mean age of 70.6±9.1. 13.1% of participants were not on statin therapy pre-CEA, and 48% of these individuals were newly prescribed one. Statin rates steadily increased throughout the study period: 36.2% in 2013 to 62% in 2021. A higher likelihood of new statin prescription was associated with non-race, diabetes, coronary heart disease, stroke, TIA and a non-elective indication. Older age, female gender, chronic obstructive pulmonary disease and prior carotid revascularisation were associated with a lower likelihood of new statin prescription. Nearly all participants were discharged on APT (63% SAPT and 37% dual antiplatelet therapy, DAPT). Among these individuals, 16% were discharged on a regimen that was different from the one on admission (11 947 (10.7%) of patients were upgraded to DAPT and 5813 (5.2%) were downgraded to SAPT).
Conclusions Although statin use has substantially improved following CEA, more than half of individuals not on a statin preprocedure remained this way at discharge. In addition, DAPT at discharge was frequent, a quarter of whom were on SAPT preprocedure. Further efforts are needed to improve rates of new statin prescriptions, ensure appropriate APT intensity at discharge and determine how different discharge APT regimens impact outcomes.
- Adult cardiology
- Thromboembolism
- Cardiology
- Stroke medicine
- Vascular medicine
- PREVENTIVE MEDICINE
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Significant variation exists in the prescription of statins and antiplatelet therapy (APT) following carotid endarterectomy (CEA), but factors associated with this variation have not been well established.
This large registry study identifies the demographic, clinical and procedural variables associated with new statin therapy as well as changes in APT regimens following CEA.
There may be discrepancies between statin/APT prescription patterns and guidelines for this at-risk population.
This study is limited by its retrospective design and availability of data. The database only recorded prescriptions at the time of discharge postprocedure and did not track medication compliance or changes in the prescription of these medications.
Introduction
Antiplatelet therapy (APT) and statin therapy have shown significant benefit for secondary prevention of cardiovascular events in patients with extracranial carotid or vertebral atherosclerosis.1–5 Presentation for carotid endarterectomy (CEA) offers an important opportunity to ensure that this high-risk population are on these cardioprotective medications.6–9 Despite a class I recommendation by the American College of Cardiology and American Heart Association (ACC/AHA) for the use of both of these medications,10 significant underutilisation for statin therapy remains.11–13 One large retrospective cohort study found that while 93% of patients were prescribed APT therapy after CEA, only 75% were prescribed a statin.11 Similarly, two other retrospective studies found that combined APT and statin utilisation following carotid artery revascularisation was only at 70%, and this was driven primarily by lower statin use.12 13 Although APT utilisation following CEA is high, prior study has suggested that significant variation in discharge APT regimens exist. As many as 20% of individuals are newly discharged on dual antiplatelet therapy (DAPT) following CEA despite no clear evidence of benefit.11 Factors influencing APT prescription regimens and the clinical effect of such variation are relatively unknown.
These studies were published using data from prior to 2015, and it is possible that trends have changed; however, this has not been formally investigated. More importantly, the clinical, demographic and procedural characteristics associated with new statin prescription or changes in APT regimen have not been studied. Using the Society of Vascular Surgery (SVS) Vascular Quality Initiative (VQI), we determined longitudinal trends in statin prescription rates as well as variations in discharge APT regimens for patients undergoing CEA. We also evaluated the clinical, demographic and procedural characteristics associated with new statin prescription and a change in APT regimen.
Methods
Study participants
We performed a retrospective, observational study within the CEA module of the VQI registry. The VQI is a large, multicentre national registry database in the USA created by the SVS with the aim to improve vascular healthcare through the collection and exchange of information among regional quality groups. Physicians and other hospital personnel enter baseline patient demographic and clinical variables, as well as procedural and postoperative variables, into a web-based data collection platform. Because data are collected under the auspices of the SVS Patient Safety Organisation, requirements for patient consent were waived. In-depth information about the SVS-VQI can be found at www.vascularqualityinitiative.org. This study was approved by the SVS-VQI Research Advisory Committee. Data were provided in an unlinked, deidentified manner and exempt from further human use review by University of Southern California institutional review board.
All patients at least 18 years of age undergoing CEA for elective or emergent indications between 2006 and early 2021 were initially considered. Records in the VQI correspond with individual procedures; a patient with multiple procedures contributes one record per event. Due to the high degree of missing data early in the study period, entries were limited to those after 2013 for final analysis. Entries with any missing data of interest were also excluded prior to multivariable analysis.
The flowchart of participants for those included in the multivariate analyses for clinical, demographic and procedural characteristics associated with new statin prescription is shown in figure 1A. Patients on a statin before their procedure had an expected high rate of statin therapy on discharge (93%). Given this outcome and our interest in identifying factors that influenced the new prescription of statin therapy, patients on baseline statin therapy (n=109 419) were excluded from logistic regression analyses. Patients not prescribed statin therapy at baseline were also excluded if they were not receiving statins for a medical reason or if they had a history of non-compliance. After the application of exclusion criteria, 16 659 procedures were included for descriptive analyses, and after removal of missing demographic data, 15 733 procedures corresponding to 15 320 patients remained for multivariate analysis (figure 1A).
Patient selection for (A) statin and (B) antiplatelet analyses. APT, antiplatelet therapy; CEA, carotid endarterectomy; DAPT, dual antiplatelet therapy; SAPT, single antiplatelet therapy.
The flowchart of participants for those included in the multivariate analyses for clinical, demographic and procedural characteristics associated with changes in APT regimen is shown in figure 1B. Patients not prescribed APT therapy at baseline due to a medical reason or if they had a history of noncompliance were excluded. Additionally, those who experienced a postoperative bleeding complication or were not discharged on APT for any reason were also excluded from the analyses. After excluding subjects with missing covariates (n=5540), we determined factors associated with new DAPT prescriptions (n=11 947) and switching from DAPT to single antiplatelet therapy (SAPT) (n=5813). Individuals not on APT at the time of CEA but appropriately discharged on SAPT were not considered as a regimen change.
Patient data
Medication use was recorded preprocedure and postprocedure. Aspirin, P2Y12 inhibitor and statin use were considered present preprocedure if the patient was on the medication with reported compliance and last use within 36 hours prior to the intervention. The use of ACE inhibitor (ACE-I) or angiotensin receptor blocker (ARB) was considered regardless of strength of therapy if the patient had documented compliance and last use within 30 days of intervention. APT and statin use were considered to be present postprocedure if the patient was started on the medication within 36 hours after the procedure.
Demographic information on age, gender, race (White, black, Asian or other), body mass index (BMI) and Insurance status (Medicare, Medicaid, Commercial or other) were collected for all procedures. Clinical variables of interest, including smoking status, hypertension, diabetes (DM), cerebrovascular disease, coronary heart disease (CHD), heart failure (HF), chronic obstructive pulmonary disease (COPD), renal impairment and history of prior carotid revascularisation (prior history of CEA or carotid artery stenting) were recorded. Smoking status was further stratified into current (use within the last month), prior (use greater than 1 month from intervention) or never. Patients with a documented history of DM were subclassified by need for insulin therapy, need for oral medications or diet-controlled. Prior neurologic event was defined by a documented history of event, regardless of residual defects. Prior eye, cortical or vertebrobasilar events were classified as either a transient ischaemic attack (TIA) or cerebrovascular accident (CVA). CHD was defined as history of coronary artery bypass grafting, percutaneous coronary intervention, myocardial infarction (MI), either stable or unstable angina or a documented stress test positive for ischaemia or infarction. HF and COPD were defined by documented history, regardless of current functional status. Renal impairment was defined by an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2, derived from the abbreviated Modification of Diet in Renal Disease equation, or the need for dialysis.14 15 Anticoagulation use was defined by documented compliance with any anticoagulant agent within the 30 days preceding procedure. Urgency of procedure was categorised as elective, urgent and emergent.
Statistical analyses
To report differences in baseline characteristics between groups, t tests and χ2 tests were performed. Multivariable Poisson regression with robust variance was used for binary outcomes to determine factors associated with (1) new statin prescription on discharge and (2) change in APT regimen at discharge. Change in APT regiment at discharge was defined as the following: (1) participants either not on any APT or on SAPT preprocedure but discharged on DAPT or (2) those on DAPT preprocedure but discharged on SAPT. Patients with complete data for all variables (listwise deletion) were included in the main analysis. A generalised estimation equation was used to account for patients with multiple procedures (around 3%) nested within the same hospitals. All demographic variables were included in the final model for analysis. BMI was categorised by clinically recognised thresholds. Continuous variable linearity assumptions were tested by fractional polynomial testing. Statistical significance was defined by a two-sided p value of 0.05. Analyses were conducted using SAS software, V.9.4 (SAS Institute).
Patient and public involvement
Patients were not involved in the development of this study. While the results will inform the medical community, there is an opportunity to share results with our patient community through social media channels.
Results
Study participants undergoing CEA were predominantly male (61%) and White (90%), with a mean age of 70.6±9.1 years (online supplemental table 1). Baseline characteristics for the 13% of individuals not on statin therapy at the time of CEA (table 1) were similar compared with the overall population. Statins were newly prescribed in 48% (n=7991) of those not on one preprocedure. Patients not taking a statin postprocedure were older, more likely to be female and had a lower prevalence of cerebrovascular disease. These patients were also more likely to have an elective indication, undergone prior carotid revascularisation and be on both antiplatelet and ACE-I or ARB therapies (table 1).
Supplemental material
Baseline characteristics of study participants not receiving statin therapy at time of intervention
Figure 2A illustrates longitudinal trends in new statin use for the study population not on a statin preprocedure. The per cent of new statin prescriptions increased from 36% in 2013 to 62% in 2021 in this population, this after performing multivariable regression analysis to adjust for all potential confounding variables. Multivariate analysis of characteristics with likelihood of new statin prescriptions following CEA is displayed in table 2. A higher likelihood of new statin prescription was associated with non-White race (Asian vs White (relative risk (RR) 1.13; 95% CI 1.06 to 1.20); black versus White (RR 1.26; 95% CI 1.11 to 1.43)), DM (oral medications versus no DM (RR 1.06; 95% CI 1.02 to 1.11)), CHD (RR 1.12; 95% CI 1.08 to 1.16), CVA (RR 1.29; 95% CI 1.22 to 1.37), TIA (RR 1.07; 95% CI 1.00 to 1.13), prior neurologic event (RR 1.10; 95% CI 1.04 to 1.17), a non-elective indication (urgent vs elective (RR 1.46; 95% CI 1.41 to 1.51); emergent versus elective (RR 1.39; 95% CI 1.27 to 1.53)) and later year of procedure (2021 vs 2013 (RR 1.62; 95% CI 1.41 to 1.90)). A lower likelihood of new statin prescription was associated with older age (71–77 vs<65 RR 0.93; 95% CI 0.89 to 0.98); ≥77 vs <65 RR 0.88; CI 0.84 to 0.93)), female gender (RR 0.95; 95% CI 0.92 to 0.99), COPD (RR 0.95; 95% CI 0.91 to 0.99) and prior carotid revascularisation (RR 0.87; 95% CI 0.82 to 0.92).
Multivariate analysis of factors associated with new statin prescription following carotid endarterectomy
New prescription rates post-CEA, 2013–2021 for (A) statin and (B) antiplatelet therapy. APT, antiplatelet therapy; CEA, carotid endarterectomy.
Only 9% individuals were not on either SAPT or DAPT therapy preprocedure and most were prescribed at least one APT agent at discharge (9463 of 12 605, 75%). Figure 2B illustrates longitudinal trends in new APT use for the study population not on APT therapy preprocedure. Baseline characteristics of individuals discharged on SAPT versus DAPT therapy are shown in online supplemental table 2. The majority were discharged on SAPT (63%, n=73 829) compared with DAPT (37%, n=40 734). Among individuals included in the multivariate analysis, 16% were discharged on a regimen that was different from the time of admission (11 947 (10.7%) of patients were upgraded to DAPT and 5813 (5.2%) were downgraded to SAPT (figure 1B)). The associations of baseline characteristics with likelihood of switching to DAPT or SAPT therapy are shown in online supplemental tables 3 and 4, respectively. While many characteristics were strongly associated with a change in discharge APT regiment, RR estimates were small and ranged between 0.95 and 1.05. Of note, individuals on SAPT preprocedure who developed perioperative MI were more likely to be discharged on DAPT (160/411, 38.9%) compared with those who did not (11 787/76 046, 15.5%).
Discussion
Nearly one-seventh of study participants were not on statin therapy prior to CEA and less than half of these were discharged on one of following the procedure. A variety of demographic and clinical characteristics were associated with likelihood of new statin prescription at discharge. Although APT prescription following CEA was nearly universal in this population, there was significant variation in discharge APT intensity (two-thirds SAPT and one-third DAPT). More importantly, approximately 16% of participants had their preprocedural APT regimen changed after CEA.
Statin therapy is recommended for all individuals undergoing CEA and has been associated with both improved long-term patency as well as reduced cardiovascular morbidity and mortality.10 In a study of nearly 7000 individuals undergoing elective CEA, the 5 year survival rate was 76% for those discharged on suboptimal medical therapy (either statin or APT, or neither) compared with 83% for those discharged on optimal medical therapy (statin and APT).12 Similarly, multiple other studies with follow-up time ranging between 1 and 10 years found a significant reduction in cardiac and cerebrovascular events for those prescribed a statin following CEA.16 17
Despite the wide-ranging, well-established benefits of statin therapy in symptomatic carotid artery disease, nearly one-seventh of study participants were not on a statin preprocedure. Annual rates of new statin prescription increased from 36% at the beginning of the study to 62% by study end, possibly indicating greater provider awareness of its importance. Overall, however, less than half of this population were newly discharged on one. Prior studies have also reported suboptimal statin therapy following CEA, though rates were lower (~75%) than that reported here, possibly due to the fact they were performed many years earlier.11–13 Our study, however, is the first to specifically look at new statin prescription rates in those not on one preprocedure. Prescribing a statin at the time of hospital discharge was shown to be the single greatest predictor of ongoing medication compliance for patients admitted with stroke.18 Institution of a system-wide quality improvement initiative in these hospitalised stroke patients such as the PROTECT programme, which included being discharged with a statin, was shown to improve vascular outcomes over as little as 3 month follow-up.19 20 While the VQI does not account for prescriptions introduced postdischarge, this research highlights the importance of identifying similar solutions that will improve new statin prescription rates immediately following CEA.
In this study, several characteristics independently and significantly predicted statin prescription following CEA. A history of DM, CHD, CVA, TIA and prior neurological event were all associated with higher statin prescription rates. It is possible that these comorbidities may have driven statin initiation rather than the procedure itself. Older age and female gender were associated with lower rates of statin prescriptions. In the USA, older adults are generally recommended lower dose, lower intensity statin therapy,21 consistent with our finding that fewer elderly patients were started on a statin. Our study is not unique in showing that women with cardiovascular disease are disproportionately underprescribed cardioprotective medications.22 23 A recent study on statin-use for the secondary prevention of cardiovascular disease showed women were particularly vulnerable to suboptimal rates, potentially due to the misperception of a higher risk of related side-effects and concerns surrounding efficacy.24 Another suggested reason for the disparity is differences in how cardiovascular risk scores are calculated based on gender.25
We also found participants residing in the southern region patients were less likely to be prescribed statins. This finding is consistent with prior studies of individuals with CHD and cerebrovascular disease.26–28 Among nearly 150 000 Medicare beneficiaries high-intensity statin claims were made in less than 50% southern residents compared with nearly 75% New England residents.26 Similarly, in an analysis of approximately 175 000 individuals admitted for stroke or TSA, those living in the south were 33% less likely to be discharged on a statin compared with those living in the west.28 No differences were found between Northeast region and Western region residents.
Current clinical practice guidelines recommend some form of APT following CEA for long-term prophylaxis against cardiovascular ischaemic events.10 Although APT prescription following CEA was nearly 100% in this population, the ratio of SAPT to DAPT at discharge was approximately 2:1. More importantly, 5% of all participants were changed from DAPT to SAPT at discharge, while nearly 10% were upgraded from SAPT to DAPT. Although we identified many demographic and clinical characteristics strongly associated with changes in APT regimen on discharge, RR estimates were small and it is difficult to put in context the clinical importance of these findings. Procedural characteristics such as periprocedural MI may have a larger role in determining conversion to DAPT. Although only a very small percentage of individuals who were not on DAPT preprocedure experienced an MI (<1%), we observed a more than twofold higher prevalence of switching to DAPT in the presence of this complication.
In contrast to carotid artery stenting recommendation, guidelines for APT post-CEA favour SAPT over DAPT.10 Recent studies have investigated the utility of intensifying to DAPT post-CEA but results have not demonstrated clear benefit. A small, single-site study of 44 patients showed no increase in bleeding and less 30-day restenosis rates.29 Another single-centre larger study also found that DAPT was associated with lower rates of restenosis when compared with SAPT but this did not translate to any difference in reintervention rate.30 Our findings raise important questions into whether, after appropriate clinical re-evaluation, more patients could have been downgraded from preprocedure DAPT and the appropriateness of such a significant number of participants on SAPT being upgraded to DAPT. Future studies need to determine how different discharge APT regimens (single vs double) and changes in APT regiments (both upgrade and downgrade) impact outcomes.
Limitations
This study is limited by its retrospective design and availability of data. The VQI only records statin use; other registries used for similar studies have the benefit of including non-statin lipid lowering drugs in analysis. Additionally, we were only able to comment on the presence or absence of statins as dosage was not known. The VQI only recorded prescriptions at the time of discharge postprocedure and did not track medication compliance or changes in the prescription of these medications. Finally, history of major bleeds, an important potential complication of APT, was not recorded.
Conclusion
Current consensus practice guidelines uniformly recommend SAPT and statin use following CEA for effective secondary prevention. Of the nearly 15% of individuals who were not on statin therapy prior to CEA, less than half were discharged on one. In addition, we observed an intensification of APT at discharge from none or SAPT to DAPT in over 10% of participants, a change seemingly not in accordance with guidelines. Further efforts are needed to (1) improve provider likelihood of new statin prescription at discharge, (2) ensure appropriate APT intensity at discharge and (3) better understand the effect variations in discharge prescription patterns for APTs and statins have on cardiovascular outcomes.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
Ethics approval
Data were provided in an unlinked, deidentified manner and exempt from further human use review by our institutional review board.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Twitter @NSingh_1218
Contributors ME, NS and PG researched literature, conceived the study, analysed the data and wrote the manuscript. LD performed statistical analysis and involved in developing results. All authors reviewed and edited the manuscript and approved the final version of the manuscript. PKG is responsible for the overall content as the guarantor.
Funding LD is supported by grant UL1TR001855 from the National Center for Advancing Translational Science (NCATS) of the US National Institutes of Health.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.