In-hospital outcomes alone underestimate rates of 30-day major adverse events after carotid artery stenting

In-hospital outcomes alone underestimate rates of 30-day major adverse events after carotid artery stenting Patric Liang, MD, Yoel Solomon, BS, Nicholas J. Swerdlow, MD, Chun Li, MD, Rens R. B. Varkevisser, BS, Livia E. V. M. de Guerre, MD, and Marc L. Schermerhorn, MD, Boston, Mass

ABSTRACT Objective: Outcome studies using databases collecting only hospital discharge data underestimate morbidity and mortality because of failure to capture postdischarge events. The proportion of postdischarge major adverse events is well characterized in patients undergoing carotid endarterectomy (CEA) but has yet to be characterized after carotid artery stenting (CAS). Methods: We retrospectively reviewed all patients undergoing CAS from 2011 to 2017 using the American College of Surgeons National Surgical Quality Improvement Program procedure targeted database to evaluate rates of 30-day major adverse events, stratified by in-hospital and postdischarge occurrences. The primary outcome was 30-day stroke/death. Multivariable analysis using purposeful selection was used to identify independent factors associated with in-hospital, postdischarge, and 30-day stroke/death events. Results: Of the 899 patients undergoing CAS, reporting of in-hospital outcomes alone would yield a stroke/death rate of 2.7%, substantially underestimating the 30-day stroke/death rate of 4.0%. In fact, 35% of stroke/deaths, 27% of strokes, 73% of deaths, 35% of cardiac events, and 35% of stroke/death/cardiac events occurred after discharge. More postdischarge stroke/death events occurred after treatment of symptomatic compared with asymptomatic patients (47% vs 27%; P < .001). During this same study period, the 30-day stroke/death rate after CEA was 2.6%, with similar proportions of postdischarge strokes (28% vs 27%; P ¼ .51) compared with CAS but lower proportions of postdischarge deaths (55% vs 73%; P < .001). After CAS, patients experiencing postdischarge stroke/death events had a shorter postoperative length of stay compared with patients with in-hospital stroke/death (1 [1-2] vs 5 [3-10] days; P < .001). Chronic obstructive pulmonary disease was independently associated with postdischarge stroke/death (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.2-16; P ¼ .02) after CAS. Nonwhite ethnicity was independently associated with overall 30-day stroke/death (OR, 3.4; 95% CI, 1.4-7.9; P < .01), whereas statin use was associated with not having stroke/death within 30 days (OR, 0.5; 95% CI, 0.2-1.0; P ¼ .049). Conclusions: More than one-quarter of perioperative strokes occur following discharge after both CAS and CEA. A higher proportion of postdischarge deaths occur after CAS in symptomatic patients, which may reflect treatment of a population of higher risk patients. Further investigation is needed to elucidate the cause of postdischarge stroke to develop methods to reduce these complications. (J Vasc Surg 2019;-:1-9.) Keywords: Carotid stenting; Carotid artery stenosis; Stroke; Cerebrovascular disease

Carotid artery stenting (CAS) has become an alternative option for carotid revascularization, especially in patients at high risk for carotid endarterectomy (CEA).1 Although multiple studies have attempted to evaluate the safety and efficacy of CAS, a discrepancy in perioperative stroke and death rates exists among these studies, given the

From the Division of Vascular and Endovascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School. P.L. is supported by the Harvard-Longwood Research Training in Vascular Surgery NIH T32 Grant 2T32HL007734. Author conflict of interest: M.L.S. is paid consulting fees (eg, advisory boards) by Silk Road, Abbott, Cook, Medtronic, and Endologix. Correspondence: Marc L. Schermerhorn, MD, Department of Surgery, Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, 110 Francis St, Ste 5B, Boston, MA 02215 (e-mail: [email protected]. edu). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvs.2019.06.201

differences in reporting of in-hospital or 30-day event rates.2-6 This is particularly evident for studies using state and nationwide registries, which are often limited to in-hospital data.7-9 In addition, because complications of surgical procedures often occur after discharge, it is important to evaluate whether the potential benefits of early discharge following a minimally invasive procedure is offset by higher rates of postdischarge events. We previously characterized the proportion of postdischarge major adverse events (MAEs) occurring after CEA and found that up to 40% of combined stroke/death events occurred after discharge in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2005 to 2010.10 However, the proportion of postdischarge events that occur within 30 days after CAS and whether the timing of these events differs from CEA are unknown. Therefore, we analyzed the ACS NSQIP vascular surgery targeted database to determine the contribution of postdischarge adverse events to overall 30-day morbidity/mortality and identified independent factors associated with the timing of these MAEs. 1

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METHODS Data set. All patients undergoing CAS in the ACS NSQIP vascular surgery targeted database were identified from January 2011 (when the targeted database was started) to December 2017. As an update to our previous study on postdischarge MAEs after CEA (before the vascular targeted database became available) and to compare postdischarge proportions between CEA and CAS during the same period, we also queried the ACS NSQIP vascular targeted CEA database. The ACS NSQIP is a multi-institutional collaboration that uses trained clinical reviewers to collect preoperative, intraoperative, and 30-day outcome data on a sampling of eligible procedures at participating hospitals. To ensure comprehensive data collection, trained clinical reviewers use a combination of electronic chart review and rigorous 30-day follow-up including phone calls to patients who do not return for follow-up within 30 days. Hospitals that participate in the targeted NSQIP database for CAS and CEA are self-selected; however, we have previously shown similar outcomes among hospitals participating in the targeted and nontargeted NSQIP database.11 Additional information on the NSQIP is available at https://www.facs.org/quality-programs/acsnsqip. Given documentation of discharge status and days to MAEs, we were able to stratify outcomes between in-hospital and postdischarge events. Patients missing data on “days to MAE” were excluded from in-hospital and postdischarge stratification, whereas 30-day outcomes included all patients in the study population without exclusions. Patients and cohorts. We identified 935 patients and 26,293 patients in the targeted NSQIP database undergoing CAS and CEA, respectively. Patients with no documentation of stent deployment (n ¼ 18 [1.9%]) and no documentation of open carotid surgery procedure method (n ¼ 31 [0.1%]) were excluded from analysis. We further analyzed patients undergoing carotid revascularization by presenting symptom status. Therefore, patients with no documentation of preoperative symptom status were also excluded (CAS, n ¼ 18 [1.9%]; CEA, n ¼ 474 [1.8%]). A list of all variable definitions captured by the NSQIP can be found at https://www.facs.org/quality-programs/ acs-nsqip. Preoperative symptom status included prior ipsilateral stroke, amaurosis fugax or transient monocular blindness, and transient ischemic attack (TIA). TIA was defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia lasting <1 hour and without evidence of acute infarction. Congestive heart failure included a new diagnosis in the past 30 days or an exacerbation before carotid revascularization. New cardiac arrhythmia included documentation of a new pathologic heart rhythm that resulted in starting a new medication, cardioversion, or placement

2019

ARTICLE HIGHLIGHTS d

d

d

Type of Research: American College of Surgeons National Surgical Quality Improvement Program national multicenter retrospective cohort study Key Finding: Of the 899 patients undergoing carotid artery stenting in the American College of Surgeons National Surgical Quality Improvement Program from 2011 to 2017, 27% of strokes, 73% of deaths, and 35% of cardiac events occurred after discharge from the hospital. Reporting of in-hospital outcomes alone would yield a stroke/death rate of 2.7%, underestimating the true perioperative 30-day stroke/death rate of 4.0%. Take Home Message: This study emphasizes the importance of reporting 30-day outcomes in evaluating postoperative major adverse events after carotid artery stenting.

of an implanted cardioverter-defibrillator or pacemaker. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate glomerular filtration rate, and chronic kidney disease was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2.12 Preoperative medications are recorded if the patient was taking the medication when considered for surgery or when surgery was decided for the patient. The NSQIP captures outcomes within 30 days of the index operation. Major individual adverse events include stroke, death, and cardiac event. Cardiac events were defined as myocardial infarction or arrhythmias. Composite outcomes included the end points of any stroke or TIA (stroke/TIA) and any stroke or death (stroke/death). Any MAE included stroke, death, or cardiac events. All outcomes were divided into those that occurred within the index hospitalization and those that occurred after discharge. Statistical analysis. Continuous variables were presented as mean 6 standard deviation or as median and interquartile range (IQR) on the basis of distribution normality. Categorial variables were presented as counts and percentages. Univariate differences between cohorts were assessed using c2 and Fisher exact tests for categorical variables and Student t-test or rank sum test for continuous variables where appropriate. We performed comparisons between in-hospital and postdischarge MAEs. Multivariable logistic regression was used to identify independent associations between baseline patient characteristics and in-hospital or postdischarge stroke/death events. The NSQIP does not capture hospital or surgeon identifiers, so clustering by center or surgeon and adjustment for volume are not possible. Purposeful selection was used to initially populate these models, which uses both univariate screen (using a P < .1

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cutoff) and previously identified factors associated with the end point of interest.13 The C statistic and HosmerLemeshow goodness-of-fit tests were used to assess the discrimination and calibration of the multivariable models, respectively. All tests were two sided, and P < .05 was considered statistically significant. Stata/SE 15.1 (StataCorp LLC, College Station, Tex) was used for all analyses. The Institutional Review Board at Beth Israel Deaconess Medical Center approved this study and waived the need for informed consent because of the retrospective, deidentified nature of the data.

RESULTS Demographics and comorbidities Of the 889 patients undergoing CAS and 25,788 undergoing CEA, 415 (46%) and 11,032 (43%) were treated for symptomatic carotid stenosis, respectively. Compared with patients undergoing CEA, CAS patients were younger (69 vs 71 years; P < .001) and less likely to be female (33% vs 39%; P < .01; Table I). However, CAS patients were more likely to be treated for symptomatic disease (46% vs 43%; P ¼ .04) and had more medical comorbidities, including chronic obstructive pulmonary disease (COPD; 16% vs 10%; P < .001), dyspnea on exertion (19% vs 13%; P < .001), chronic heart failure (5.2% vs 1.4%; P < .001), and diabetes mellitus (35% vs 31%; P < .01). They were also more likely to be taking aspirin (94% vs 90%; P < .001) and beta blocker (59% vs 55%; P ¼ .03) preoperatively. CAS procedures were less likely to be performed by vascular surgeons (91% vs 95%; P < .001) and less likely to be performed under general anesthesia (31% vs 86%; P < .001). The remaining CAS procedures were performed by neurosurgeons (7.9%) and interventional radiologists (5.2%). Median postoperative length of stay was similar for CEA and CAS (1 [1-2] day vs 1 [1-2] day; P ¼ .09). Outcomes and timing for MAEs CAS. After CAS, the 30-day stroke rate was 3.2%, mortality rate was 1.2%, cardiac event rate was 2.2%, stroke/ death rate was 4.0%, and any MAE rate was 5.9% (Table II). Composite stroke/death occurred after discharge in 35% of patients. Postdischarge stroke/death occurred at a median of 13 days (IQR, 6-18 days), whereas in-hospital stroke/death often occurred during the immediate perioperative period (median, 0 day; IQR, 0-1 day; Fig). Any in-hospital MAEs occurred in 3.9% of patients undergoing CAS. After discharge, an additional 2.1% of patients developed stroke, death, or cardiac event, accounting for 35% of all MAEs that occurred within 30 days of the procedure. Stroke was the most common 30-day MAE (3.2%), but death had the longest median time to event at 14 days, with the majority of deaths occurring after discharge; 27% of strokes, 73% of deaths, 35% of stroke/death, and 35% of cardiac events occurred after discharge.

Table I. Preoperative characteristics of patients undergoing carotid artery stenting (CAS) and carotid endarterectomy (CEA)

Age, years Age >80 years

CAS (n ¼ 899)

CEA (n ¼ 25,788)

69 6 10

71 6 9.2

13

17

<.01

P value <.001

Female

33

39

<.01

White ethnicity

91

93

.01

Symptomatic

46

43

.04

Stroke

21

20

.49

TIA

26

23

.08

Hypertension

84

83

.82

COPD

16

10

<.001

Dyspnea on exertion

19

13

Chronic heart failure

5.2

1.4

<.001 <.001

Smoking

29

27

.13

Diabetes mellitus

35

31

.01

BMI, kg/m2 BMI >40 kg/m2 Chronic kidney disease

29 6 6.2 5.5 33

29 6 5.7 5.6 35

.93 .88 .23

Dialysis dependence

1.3

1.1

.54

Dependent functional status

4.3

2.7

<.01

General anesthesia

31

86

<.001

Vascular surgeon

91

95

<.001

Preoperative medications Steroid

3.7

3.1

.36 <.001

Aspirin

94

90

Statin

82

82

.68

Beta blocker

59

55

.03

BMI, Body mass index; COPD, chronic obstructive pulmonary disease; TIA, transient ischemic attack. Categorical variables are presented as percentage. Continuous variables are presented as mean 6 standard deviation.

CEA. The 30-day stroke rate after CEA was 2.1%, mortality rate was 0.7%, cardiac event rate was 1.7%, stroke/death rate was 2.6%, and overall MAE rate was 4.0%. Any in-hospital MAEs occurred in 2.9% of patients undergoing CEA. After discharge, an additional 1.2% of patients developed additional stroke, death, or cardiac event, accounting for 30% of all MAEs occurring within 30 days. Similar to CAS, stroke was the most common 30-day MAE and death had the longest median time to event at 9 days, with the majority of deaths occurring after discharge; 28% of strokes, 55% of deaths, 30% of stroke/death, and 29% of cardiac events occurred after discharge. Compared with CEA, a similar proportion of postdischarge strokes occurred after CAS (27% vs 28%; P ¼ .51; Table III). However, CAS had a significantly higher proportion of postdischarge deaths (73% vs 55%;

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Table II. Outcome and timing of in-hospital, postdischarge, and 30-day major adverse events (MAEs) of patients undergoing carotid artery stenting (CAS) and carotid endarterectomy (CEA) Time to event, days

In-hospital event rate, No. (%)

Mean 6 SD

Median (IQR)

Postdischarge event rate, No. (%)

30-Day event rate, No. (%)

Proportion of events that occurred after discharge, %

CAS (n ¼ 899) Stroke

1 (0-3)

3.1 6 5.5

19 (2.1)

Stroke/TIA

1 (1-6)

4.5 6 7.3

23 (2.6)

14 (8-21)

14.5 6 7.6

3 (0.3)

Death

7 (0.8)

29 (3.2)

27

38 (4.2)

34

8 (0.9)

11 (1.2)

73

7 (0.8)

12 (1.3)

Cardiac event

2 (1-7)

4.9 6 5.8

13 (1.5)

20 (2.2)

35

Stroke/death

2 (0-12)

6.6 6 8.6

24 (2.7)

13 (1.5)

36 (4.0)

35

Any MAE

2 (0-9)

5.9 6 7.7

35 (3.9)

19 (2.1)

53 (5.9)

35

1 (0-5)

3.9 6 6.2

358 (1.4)

139 (0.5)

540 (2.1)

28

CEA (n ¼ 25,788) Stroke Stroke/TIA

1 (0-6)

4.5 6 6.5

449 (1.7)

236 (0.9)

748 (2.9)

34

Death

9 (4-17)

11 6 8.1

80 (0.3)

98 (0.4)

178 (0.7)

55

Cardiac event

2 (1-4)

4.5 6 6.7

308 (1.2)

123 (0.5)

439 (1.7)

29

Stroke/death

2 (0-9)

5.5 6 7.2

493 (1.9)

214 (0.8)

660 (2.6)

30

Any MAE

2 (0-6)

5.0 6 7.0

744 (2.9)

313 (1.2)

1021 (4.0)

30

IQR, Interquartile range; SD, standard deviation; TIA, transient ischemic attack. The 30-day results include events occurring in all patients during the follow-up period. In-hospital and postdischarge events exclude patients with unknown postoperative days to event.

14

12

Frequency

10

8

6

4

2

0 0

1

2

3

4

5

6

7

8

9

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Days from Interven on un l Stroke/Death In-hospital

Post-discharge

Fig. Days from carotid stenting until in-hospital or postdischarge stroke.

P < .001) and cardiac events (35% vs 29%; P < .001). For the composite end point of stroke/death, CAS was found to have a higher proportion of postdischarge occurrences (35% vs 30%; P < .01). Symptom status CAS. For asymptomatic patients, any in-hospital MAE occurred in 3.9% of patients undergoing CAS, with an additional 1.9% having MAEs after discharge (Table IV). For symptomatic patients, any in-hospital MAE occurred

in 3.9%, with an additional 2.4% of patients developing postdischarge MAEs. Asymptomatic patients had a trend toward a lower proportion of postdischarge MAEs compared with symptomatic patients (32% vs 38%; P ¼ .06). The majority of adverse events occurred in the hospital for asymptomatic patients, whereas for symptomatic patients, 86% of deaths occurred after discharge. Death remained the longest time to event for both groups, with a median of 14 days for both asymptomatic and

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Table III. Proportion of postdischarge stroke/death for patients by procedure CAS (n ¼ 889), %

CEA (n ¼ 25,788), %

Stroke

27

28

.51

Stroke/TIA

34

34

1.00

P value

Death

73

55

<.001

Cardiac event

35

29

<.001

Stroke/death

35

30

<.01

Any MAE

35

30

<.01

CAS, Carotid artery stenting; CEA, carotid endarterectomy; MAE, major adverse event; TIA, transient ischemic attack.

symptomatic patients. Asymptomatic patients had lower proportions of stroke/death occurring after discharge compared with symptomatic patients (27% vs 47%; P < .001), including the individual outcomes of stroke (22% vs 38%; P < .001) and death (50% vs 86%; P < .001). CEA. For asymptomatic patients, in-hospital MAEs occurred in 2.2% of patients undergoing CEA, with an additional 1.1% of MAEs occurring after discharge (Table V). For symptomatic patients, in-hospital MAEs occurred in 3.8% of patients, with an additional 1.3% of patients developing postdischarge MAEs. In contrast to CAS, asymptomatic patients undergoing CEA had higher proportions of postdischarge MAEs compared with symptomatic patients (34% vs 26%; P < .001). More than 50% of MAEs occurred in the hospital for both groups, except for death, of which 64% occurred after discharge for asymptomatic patients. Compared with symptomatic patients, asymptomatic patients had higher proportions of postdischarge stroke (30% vs 27%; P < .001) and higher proportions of postdischarge deaths (64% vs 49%; P < .001) and cardiac events (31% vs 25%; P < .001; Table VI). Factors associated with stroke/death for CAS No preoperative or intraoperative factors were found to be independently associated with in-hospital stroke/ death. COPD was independently associated with postdischarge hospital stroke/death after CAS (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.2-16; P ¼ .02; Table VII), whereas nonwhite ethnicity was independently associated with overall 30-day stroke/death (OR, 3.4; 95% CI, 1.4-7.9; P < .01). Statin use was independently associated with lower stroke/deaths within the 30-day postoperative period (OR, 0.5; 95% CI, 0.2-1.0; P ¼ .049).

DISCUSSION In this study, we demonstrate that a significant number of MAEsdmost important, 35% of stroke/death eventsd occur following discharge from the hospital after CAS. However, in contrast to CEA, the rates of postdischarge stroke/death after CAS are disproportionally driven by treatment in symptomatic patients, with up to 38% of

strokes and 86% of deaths occurring in the postdischarge period. After CAS, COPD was independently associated with postdischarge stroke/death, and nonwhite ethnicity was associated with overall 30-day stroke/death. Preoperative statin use was protective for 30-day stroke/death. The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) reported a 30-day stroke rate of 4.1% after CAS,6 whereas in-hospital data from the Vascular Quality Initiative (VQI) from 2005 to 2017 reported a lower stroke rate of 2.0%.14 The twofold difference in stroke rate after CAS between CREST and VQI may be attributed to 30-day outcome reporting in CREST compared with in-hospital reporting for VQI database studies (Table VIII). Similarly, data from the National Inpatient Sample between the years 2005 and 2007 revealed an even lower periprocedural CAS stroke rate of 1.4%.2 Studies using administrative data sets such as the National Inpatient Sample collect only hospital discharge data and can therefore under-report the morbidity and mortality that follow carotid revascularization. These administrative data sets are also inaccurate at determining preoperative symptom status and postoperative stroke and therefore should not be used to compare procedural outcomes or to estimate the proportion of symptomatic patients undergoing carotid revascularization in the United States.23 In contrast, registries such as the NSQIP evaluate 30-day outcomes. We found that reporting of in-hospital outcomes alone in the NSQIP would yield a stroke rate of 2.1% after carotid stenting, which would underestimate the 30-day stroke rate of 3.2%. Similarly, for the combined end point of stroke/death, evaluating only in-hospital outcomes of 2.7% would substantially underestimate the true 30-day stroke/death rate of 4.0%, as 73% of deaths were found to occur following discharge after carotid stenting. Although the 3.2% 30-day stroke rate found in this study remains lower than the 4.1% stroke rate found in CREST, the 4.0% composite stroke/ death rate found in this study more closely approximates the 4.4% stroke/death rate reported in CREST. The remaining difference in stroke rates may be explained by under-reporting of postoperative neurologic events outside of clinical trials. Whereas the NSQIP does not require institutions to perform formal neurologic evaluations after carotid revascularization, postoperative mortality is not subject to a similar reporting bias. We have previously reported the impact of postdischarge MAEs on CEA in the nontargeted NSQIP from 2005 to 2010 and found that 38% of perioperative adverse events occur after discharge, including 40% of stroke/deaths.10 This study provides an updated analysis of the NSQIP database by using the vascular surgery targeted database from 2011 to 2017, confirming similar proportions of postdischarge events for all MAE categories after CEA. However, the significance of postdischarge

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Table IV. Outcome and timing of in-hospital, postdischarge, and 30-day major adverse events (MAEs) of patients undergoing carotid artery stenting (CAS) by symptom status Median (IQR)

Mean 6 SD

Time to event, days

In-hospital event rate, No. (%)

Postdischarge event rate, No. (%)

30-Day event rate, No. (%)

Proportion of events that occurred after discharge, % 22

Asymptomatic (n ¼ 484) Stroke

1 (0-4)

3.3 6 6.1

14 (2.9)

4 (0.8)

18 (3.7)

Stroke/TIA

1 (0-5)

4.1 6 7.0

15 (3.1)

5 (1.0)

20 (4.1)

14 (9-20)

14 6 6.5

Death

2 (0.4)

2 (0.4)

25

4 (0.8)

50

Cardiac event

3 (2-7)

4.8 6 4.9

5 (1.0)

3 (0.6)

8 (1.7)

38

Stroke/death

1 (0-8)

5.6 6 7.9

16 (3.3)

6 (1.2)

21 (4.3)

27

Any MAE

2 (0-8)

5.7 6 7.3

19 (3.9)

9 (1.9)

27 (5.6)

32 38

Symptomatic (n ¼ 415) Stroke

2 (0-3)

2.8 6 4.3

5 (1.2)

3 (0.7)

11 (2.7)

Stroke/TIA

2 (0-7)

5.0 6 7.9

8 (1.9)

7 (1.7)

18 (4.3)

47

14 (7-22)

15 6 8.7

1 (0.2)

6 (1.5)

7 (1.7)

86

Cardiac event

2 (1-8)

4.9 6 6.5

8 (1.9)

4 (1.0)

12 (2.9)

33

Stroke/death

3 (0-13)

7.8 6 9.5

8 (1.9)

7 (1.7)

15 (3.6)

47

Any MAE

3 (1-10)

6.2 6 8.1

16 (3.9)

10 (2.4)

26 (6.3)

38

Death

IQR, Interquartile range; SD, standard deviation; TIA, transient ischemic attack.

Table V. Outcome and timing of in-hospital, postdischarge, and 30-day major adverse events (MAEs) of patients undergoing carotid endarterectomy (CEA) by symptom status Median (IQR)

Mean 6 SD

Time to event, days

In-hospital event rate, No. (%)

Postdischarge event rate, No. (%)

30-Day event rate, No. (%)

Proportion of events that occurred after discharge, % 30

Asymptomatic (n ¼ 14,756) Stroke

1 (0-6)

4.3 6 6.7

129 (0.9)

56 (0.4)

190 (1.3)

Stroke/TIA

1 (0-7)

4.5 6 6.4

158 (1.1)

92 (0.6)

259 (1.8)

37

Death

8 (3-19)

12 6 9.4

28 (0.2)

49 (0.3)

77 (0.5)

64

Cardiac event

2 (1-5)

4.6 6 6.7

173 (1.2)

77 (0.5)

Stroke/death

2 (0-9)

6.1 6 7.8

177 (1.2)

Any MAE

2 (1-7)

5.3 6 7.3

329 (2.2)

1 (0-4)

3.6 6 6.0

229 (2.1)

Stroke/TIA

1 (0-6)

4.5 6 6.6

291 (2.6)

Death

9 (5-16)

11 6 7.0

52 (0.5)

253 (1.7)

31

101 (0.7)

255 (1.7)

36

168 (1.1)

478 (3.2)

34

350 (3.2)

27

Symptomatic (n ¼ 11,032) Stroke

83 (0.8) 144 (1.3) 49 (0.4)

489 (4.4)

33

1.1 (0.9)

49

Cardiac event

2 (1-4)

4.4 6 6.8

135 (1.2)

46 (0.4)

186 (1.7)

25

Stroke/death

2 (0-8)

5.2 6 6.9

316 (2.9)

113 (1.0)

405 (3.7)

26

Any MAE

2 (0-6)

4.7 6 6.7

415 (3.8)

145 (1.3)

543 (4.9)

26

IQR, Interquartile range; SD, standard deviation; TIA, transient ischemic attack. The 30-day results include events occurring in all patients during the follow-up period. In-hospital and postdischarge events exclude patients with unknown postoperative days to event.

events after CAS is less well characterized in the current literature. Similar to CEA, CAS offers a swift method of carotid revascularization, with most patients discharged within 2 days of the procedure. Although it is beneficial for hospitals in terms of cost savings with early discharge after carotid revascularization,24 significant patient care

implications can ensue if a high proportion of MAEs occur after discharge. Early results from the Society for Vascular Surgery Vascular Registry from 2005 to 2007 found that after carotid stenting, 31% of combined stroke, death, and cardiac events were not captured during a hospital

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Table VI. Proportion of postdischarge stroke/death for patients by symptom status for carotid artery stenting (CAS) and carotid endarterectomy (CEA) CAS

CEA

Asymptomatic (n ¼ 484), %

Symptomatic (n ¼ 415), %

P value

Asymptomatic (n ¼ 14,756), %

Symptomatic (n ¼ 11,032), %

P value

Stroke

22

38

<.001

30

27

<.001

Stroke/TIA

25

47

<.001

37

33

<.001

Death

50

86

<.001

64

49

<.001

Cardiac event

38

33

.12

31

25

<.001

Stroke/death

27

47

<.001

36

26

<.001

Any MAE

32

38

.06

34

26

<.001

MAE, Major adverse event; TIA, transient ischemic attack.

Table VII. Independent factors associated with stroke/death for patients undergoing carotid artery stenting (CAS) In-hospital event

Female

Postdischarge event

OR

95% CI

P value

OR

95% CI

P value

30-day event OR

95% CI

P value

0.9

0.4-2.2

.83

2.7

0.7-9.6

.13

0.9

0.4-2.0

.86

Nonwhite

1.2

0.3-4.2

.78

2.0

0.4-10

.41

3.4

1.4-7.9

<.01

Smoking

0.2

0.1-1.0

.05

1.4

0.4-5.0

.56

0.6

0.2-1.4

.21

1.8

0.8-4.0

.18

0.6

0.2-2.5

.53

0.9

0.4-1.9

.73

COPD

0.8

0.2-3.9

.80

4.4

1.2-16

.02

1.7

0.7-4.2

.23

Aspirin use

0.8

0.2-3.9

.80

0.3

0.1-1.8

.19

0.6

0.2-2.0

.43

Statin use

0.9

0.3-2.5

.79

0.3

0.1-1.1

.08

0.5

0.2-1.0

.049

General anesthesia

CI, Confidence interval; COPD, chronic obstructive pulmonary disease; OR, odds ratio.

admission; however, this study was beset by poor 30-day follow-up.25 Our study, with complete 30-day follow-up in the NSQIP, confirms a similarly high proportion of postdischarge MAEs after CAS (35%). In addition, we found that aside from cardiac events, the proportion of postdischarge events was significantly higher after treatment of symptomatic patients compared with their asymptomatic counterparts. The higher proportion of postdischarge events for symptomatic patients may be due to delayed microembolization through stent struts in unstable plaques or delayed diagnosis secondary to residual presenting neurologic deficits. Further studies are needed to better clarify these discrepancies. Regardless, these findings suggest that symptomatic patients undergoing carotid stenting warrant especially close follow-up throughout the postoperative period. Different demographics and comorbidities affect occurrence of in-hospital and postdischarge adverse events. COPD was found to be a factor independently associated with postdischarge stroke/death, whereas white race and statin use were found to be protective against overall 30-day stroke/death. Although COPD is not an easily modifiable risk factor, efforts in respiratory optimization before surgery may assist in reducing postdischarge events. On the other hand, medical

optimization, including dose-dependent use of statins, not only has a central role in overall stroke prevention in patients with carotid disease but also has been found to have benefits after carotid stenting.26 Other studies have also identified that black and Hispanic patients have higher rates of MAEs after CAS, including higher risk of death for Hispanic patients and higher stroke rates for black patients.27,28 Multiple comorbid and socioeconomic factors may contribute to these racial differences, but this is beyond the scope of this study. This study must be interpreted in the context of its design and the database used. The NSQIP database is subject to miscoding by the trained clinical nurse reviewers. However, we have previously shown that nontargeted NSQIP reviewers are accurate in differentiating preoperative symptom status and postoperative stroke but are not accurate in identifying high-risk patients (eg, stage of congestive heart failure).23 Identification of high-risk patients has been addressed with the targeted vascular NSQIP database. There was no randomization between treatment options, given the retrospective nature of this study, so the treating physician was responsible for selecting the revascularization method. However, our intent was not to compare outcomes of CEA and CAS but to clarify the proportions of adverse events

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Table VIII. Any postoperative stroke after carotid artery stenting (CAS) stratified by study follow-up lengths Database or trial

Type of study

Study period

Total CAS patients

NIS2

Retrospective

2005-2007

46,085

VQI

Retrospective

2005-2017

10,136

42

In-hospital

2.0

NSQIP

Retrospective

2011-2017

899

46

In-hospital

2.1

VQI15

Retrospective

2003-2016

8519

43

30 days

2.2

ACT 116

Randomized

2005-2013

1089

0

30 days

2.8

NSQIP

Retrospective

2011-2017

899

46

30 days

3.2

14

17

Symptomatic, % 8

Follow-up

Stroke rate, %

In-hospital

1.4

Randomized

2000-2002

159

30

30 days

3.6

CREST6

Randomized

2005-2008

1262

53

30 days

4.1

SPACE18

Randomized

2001-2006

599

100

30 days

7.5

EVA-3S4

Randomized

2000-2005

261

100

30 days

9.2

ICSS19

Randomized

2001-2008

853

100

3 months

7.7

ICSS19

Randomized

2001-2008

853

100

1 year

9.5

SAPPHIRE17

Randomized

2000-2002

159

30

SPACE20

Randomized

2001-2006

607

100

SAPPHIRE21

Randomized

2000-2002

159

30

3 years

10.1

CREST6

Randomized

2005-2008

1262

53

4 years

10.2

ICSS19

Randomized

2001-2008

853

100

CREST22

Randomized

2005-2008

1262

53

SAPPHIRE

1 year 2 years

6.2 10.9

5 year

15.2

10 years

10.8

ACT, Asymptomatic Carotid Trial; CREST, Carotid Revascularization Endarterectomy vs Stenting; EVA-3S, Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis; NIS, National (Nationwide) Inpatient Sample; NSQIP, National Surgical Quality Improvement Program; SAPPHIRE, Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy; SPACE, Stent-Supported Percutaneous Angioplasty vs Endarterectomy; VQI, Vascular Qualitive Initiative.

occurring after discharge. The NSQIP is limited to 30-day events, and therefore events occurring after 30-day follow-up are not captured in this study. Although a significant number of adverse events were already identified with this study, it would underestimate the number of postdischarge events if longer follow-up data were available. In addition, this study is limited to the predefined patient characteristics and intraoperative and postoperative variables available in the NSQIP, so it is possible that additional variables may be left unaccounted for in our multivariable models.

CONCLUSIONS This study emphasizes the importance of reporting 30-day outcomes in evaluating postoperative MAEs after CAS because a significant number of MAEs occur following discharge after CAS, especially for symptomatic patients. However, the proportion of postdischarge stroke events after CAS is similar to that of CEA. Physicians should be attentive to postdischarge adverse events with close follow-up. Future investigation is needed to determine the cause of postdischarge stroke in efforts to reduce these complications.

AUTHOR CONTRIBUTIONS Conception and design: PL, YS, NS, LG, MS Analysis and interpretation: PL, YS, NS, CL, RV, LG, MS Data collection: PL, YS, CL, RV, LG, MS

Writing the article: PL, YS Critical revision of the article: PL, YS, NS, CL, RV, LG, MS Final approval of the article: PL, YS, NS, CL, RV, LG, MS Statistical analysis: PL, YS Obtained funding: Not applicable Overall responsibility: PL PL and YS contributed equally to this article and share co-first authorship.

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Submitted Feb 6, 2019; accepted Jun 30, 2019.