Abstract
Objectives:
Current data on outcomes after transfemoral carotid artery stenting (TFCAS) originate from the early experience with TFCAS. Whereas most prior studies stratify outcomes based on symptomatic or asymptomatic presentation, they often do not specify the degree of presenting neurologic injury. While we previously reported that outcomes after carotid endarterectomy differ based on neurologic injury severity, the contemporary perioperative outcomes of TFCAS stratified by specific presenting symptom status are unknown.
Methods:
Patients within the Vascular Quality Initiative database undergoing TFCAS between 2016 and 2020 were included. We stratified patients based on their pre-procedural symptom status as either asymptomatic, formerly symptomatic (last symptoms >180 days prior to procedure), or recently symptomatic (symptom <180 days prior to procedure), including either stroke, hemispheric transient ischemic attack (TIA), or ocular TIA. We compared occurrences of in-hospital stroke or death (stroke/death) between asymptomatic, formerly symptomatic, and specific subtypes of recently symptomatic patients. Multivariable logistic regression models were constructed to adjust for baseline differences between groups.
Results:
Out of 9,807 included patients, 2,650 (27%) had recent stroke, 842 (9%) had recent hemispheric TIA, 360 (4%) had recent ocular TIA, 795 (8%) were formerly symptomatic, and 5,160 (53%) were asymptomatic. Patients with recent stroke had a perioperative stroke/death rate of 5.5%, which was higher compared with patients with recent hemispheric TIA (2.4%; P<.001), recent ocular TIA (2.8%; P = .03), or asymptomatic patients (1.4%; P<.001). Stroke/death was higher in patients with recent ocular TIA compared with asymptomatic patients (2.8% vs. 1.4%; P = .04). Formerly symptomatic patients had higher stroke/death rates compared with asymptomatic patients (3.5% vs. 1.4%; P<.001). In multivariable adjusted analysis, recent stroke was associated with higher stroke/death compared with recent hemispheric TIA (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.6–4.3; P<.001), and asymptomatic status (OR 4.1; 95% CI 3.0–5.6; P<.001), while demonstrating a trend towards higher stroke/death compared with recent ocular TIA (OR 2.0; 95% CI 1.0–3.9; P = .06). Furthermore, asymptomatic status was associated with lower stroke/death compared with formerly symptomatic status (OR 0.4; 95% CI: 0.2–0.6; P<.001).
Conclusions:
In patients undergoing TFCAS, recent stroke was associated with higher odds of in-hospital stroke/death after TFCAS compared with recent hemispheric TIA, and a formerly symptomatic status was associated with higher odds of stroke/death compared with an asymptomatic status. These findings support further symptom stratification based on the degree of presenting neurological injury in pre-operative risk-assessment.
Summary
This retrospective, multi-center study with 9,807 patients provides an update on contemporary outcomes after transfemoral carotid artery stenting stratified by specific pre-procedural symptom status. It reveals that outcomes differ between patients with specific symptoms within the symptomatic cohort, advocating for further stratification within this cohort to improve pre-operative risk assessment.
INTRODUCTION
Trials investigating outcomes after carotid revascularization generally stratify the patient population as either symptomatic or asymptomatic.1,2 However, patients with symptomatic carotid artery disease can present with various degrees of neurological injury such as stroke, hemispheric transient ischemic attack (TIA), and ocular TIA. Additionally, several studies have defined patients as asymptomatic if their neurological event was more than 180 days prior to trial enrollment (formerly symptomatic). When compared with asymptomatic carotid artery disease, symptomatic carotid artery disease is associated with increased adverse procedural outcomes after carotid revascularization such as stroke or death (stroke/death).3,4 To prevent stroke in patients with carotid artery disease, transfemoral carotid artery stenting (TFCAS) is a minimally invasive alternative to carotid endarterectomy (CEA), which is the gold standard for carotid revascularization.
Since its approval by the United States Food and Drug Administration in 2004,5 TFCAS has been subject to continuous technologic and procedural improvements. The safety and efficacy of TFCAS has been evaluated against CEA in randomized clinical trials.1,6 In these trials, patients undergoing TFCAS were categorized as symptomatic or asymptomatic.2,6–8 However, in symptomatic patients undergoing TFCAS or CEA, further stratification into their specific pre-procedural symptom (stroke, hemispheric TIA, or ocular TIA), showed that perioperative outcomes differed among patients based on symptom type.3 This finding suggests that stratification by specific pre-procedural symptoms may be more accurate than the common binary symptomatic/asymptomatic stratification. Although a study on the incidence of perioperative outcomes after CEA stratified by specific symptom status has been published recently,4 existing data in patients undergoing TFCAS originate from the early years of 2004–2011.3 Furthermore, while a study including patients between 2000–2008 demonstrated that the stroke/death rate was similar in asymptomatic vs. formerly symptomatic patients, the study had a small sample size and a very low event rate.9 In addition, the accuracy of stratifying formerly symptomatic patients as asymptomatic in trials has not been validated in the contemporary setting. Therefore, this study aimed to provide an update on contemporary perioperative outcomes after TFCAS stratified by specific pre-procedural symptoms in a real-world setting of a large clinical registry with granular details and prospective data collection.
METHODS
Registry
We used data from the Vascular Quality Initiative (VQI), which is a clinical registry across the United States, Canada, and Singapore. The registry was established as a collaboration of regional quality care groups to improve patient care through prospectively collected clinical data of common vascular procedures. Data, including patient characteristics, procedure information, and in-hospital outcomes, are captured in over 200 variables. In February 2019 the VQI included over 530 participating centers in 18 regions. The Institutional Review Board at Beth Israel Deaconess Medical Center approved this study and waived the need for informed consent due to the retrospective, de-identified nature of the data.
Patients and variables
Due to limited granularity of data on symptom status in patients undergoing TFCAS prior to 2016, we included patients who underwent TFCAS starting from 2016. A total of 15,367 patients undergoing TFCAS between January 2016 and February 2020 were identified. We excluded patients with insufficient data on ipsilateral pre-procedural symptom status (N = 4,438, 29%), patients with prior vertebrobasilar events (N = 29, <1%), patients with traumatic, dissection, or fibromuscular dysplasia lesions (N = 676, 4%), patients with concomitant intracranial procedures (N = 409, 3%), and patients under the age of 18 years (N = 8, <1%).
We defined patients with an ipsilateral neurologic symptom within the first 180 days prior to the procedure as recently symptomatic, and patients with an ipsilateral neurologic symptom over 180 days prior to procedure as formerly symptomatic. Recently symptomatic patients were further stratified into one of the following groups: recent stroke, recent hemispheric TIA, or recent ocular TIA. A recent stroke was defined as ocular or cortical symptoms lasting more than 24 hours. Recent hemispheric TIA was defined as ocular or cortical symptoms lasting a maximum of 24 hours. Recent ocular TIA was defined as solely having a full or partial visual loss due to a retinal embolism. Patients who experienced more than one type of symptom were grouped according to their most severe symptom in the following order of severity: stroke, hemispheric TIA, ocular TIA. The estimated glomerular filtration rates (eGFR) were calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.10
Formerly symptomatic patients were compared with asymptomatic patients and the combined group of recently symptomatic patients (i.e., patients with either a recent stroke, recent hemispheric TIA, or recent ocular TIA). As specific pre-procedural symptoms might influence comparisons between formerly and recently symptomatic patients, we added a stroke/death rate comparison between the formerly and recently symptomatic patient cohorts, stratified by specific pre-procedural symptoms. Our primary outcome was the in-hospital stroke or death (stroke/death) rate. Secondary outcomes were in-hospital stroke, death, myocardial infarction (MI) and length of hospital stay of over two days (prolonged LOS).
Statistical analysis
Categorical variables are presented as numbers and percentages, and continuous variables are presented as mean ± standard deviation for normally distributed variables or as median and interquartile range (IQR) for non-normally distributed variables. Bivariable differences were tested with the Student’s t-test or Wilcoxon rank-sum test for continuous variables, where appropriate. The χ2 or Fisher’s exact tests were used for categorical variables where appropriate. Bivariable analyses were two tailed and were considered statistically significant if α < .05.
We used multivariable adjusted analysis to assess the risk-adjusted association between pre-procedural symptom status and in-hospital stroke/death. Previously identified risk factors were selected in the model a priori, and included age, sex, race, hypertension, diabetes mellitus, congestive heart failure, coronary artery disease, current smoking status, chronic obstructive pulmonary disease (COPD), pre-operative dialysis, and eGFR < 30 mL/min. All baseline variables were missing in less than four percent of patients. All analyses were performed using Stata version 14.2 (StataCorp LP, College Station, TX).
RESULTS
Patient characteristics
A total of 9,807 patients undergoing TFCAS were included in the analysis. Median age was 70 years (IQR: 64, 77), 3,509 (36%) patients were female, and 732 (7%) patients were non-white. Stratified by pre-procedural symptoms, 2,650 (27%) patients had recent stroke, 842 (9%) patients had recent hemispheric TIA, 360 (4%) patients had recent ocular TIA, 795 (8%) patients were formerly symptomatic, and 5,160 (53%) patients were asymptomatic. Patient characteristics are presented in Table I.
Table I:
Univariate analysis of patient characteristics and procedural details stratified by specific pre-procedural symptom status
| 1. Stroke | 2. Hemispheric TIA | 3. Ocular TIA | P-value 1 vs. 2 vs. 3 | 4. Asymptomatic | 5. Formerly Symptomatic | 6. Recently Symptomatic | P-value 4 vs. 5 vs. 6 | |
|---|---|---|---|---|---|---|---|---|
| N | 2650 | 842 | 360 | 5160 | 795 | 3852 | ||
| Age, median (IQR) | 69 (62, 77) | 72 (65, 79) | 68 (62, 76) | <.001 | 71 (64, 76) | 70 (63, 76) | 70 (63, 77) | .06 |
| Female sex | 929 (35.1) | 326 (38.7) | 108 (30.0) | .01 | 1842 (35.7) | 304 (38.2) | 1363 (35.4) | .31 |
| Non-white race | 280 (11.0) | 63 (7.7) | 16 (4.5) | <.001 | 322 (6.5) | 51 (6.6) | 359 (9.7) | <.001 |
| Obese (BMI >30) | 981 (37.3) | 282 (33.6) | 122 (34.2) | .11 | 1814 (35.3) | 267 (33.7) | 1385 (36.2) | .36 |
| Underweight (BMI <18.5) | 72 (2.7) | 15 (1.8) | 6 (1.7) | .19 | 119 (2.3) | 20 (2.5) | 93 (2.4) | .90 |
| Hypertension | 2287 (86.3) | 742 (88.2) | 314 (87.2) | .36 | 4542 (89.6) | 720 (90.6) | 3343 (86.8) | <.001 |
| Diabetes with insulin use | 452 (17.1) | 123 (14.6) | 45 (12.5) | .04 | 769 (14.9) | 121 (15.2) | 620 (16.1) | .32 |
| Any diabetes | 1045 (39.4) | 322 (38.2) | 120 (33.4) | .09 | 2042 (39.7) | 312 (39.2) | 1487 (38.6) | .59 |
| Current smoker | 866 (32.8) | 212 (25.2) | 119 (33.1) | <.001 | 1218 (23.6) | 211 (26.5) | 1197 (31.2) | <.001 |
| COPD | 629 (23.7) | 231 (27.4) | 117 (32.5) | <.001 | 1439 (27.9) | 214 (26.9) | 977 (25.4) | .03 |
| CHF | 401 (15.1) | 148 (17.6) | 50 (13.9) | .15 | 881 (17.1) | 142 (17.9) | 599 (15.6) | .09 |
| CAD | 925 (34.9) | 368 43.7) | 155 (43.1) | <.001 | 2446 (48.1) | 372 (46.8) | 1448 (37.6) | <.001 |
| Pre-procedural renal function | <.001 | <.001 | ||||||
| eGFR >60 mL/min | 1885 (72.2) | 522 (62.7) | 248 (70.1) | 3262 (64.1) | 494 (63.3) | 2655 (69.9) | ||
| eGFR 30–60 mL/min | 612 (23.4) | 276 (33.2) | 92 (26.0) | 1608 (31.6) | 258 (33.0) | 980 (25.8) | ||
| eGFR <30 mL/min | 72 (2.8) | 18 (2.2) | 13 (3.7) | 158 (3.1) | 22 (2.8) | 103 (2.7) | ||
| On dialysis | 41 (1.6) | 16 (1.9) | 1 (0.3) | 64 (1.3) | 7 (0.9) | 58 (1.5) | ||
| Acute procedure (in ≤14 days) | 1759 (66.4) | 429 (51.0) | 131 (36.4) | <.001 | 2319 (60.2) | |||
| Pre-procedural medication | ||||||||
| Aspirin | 2180 (82.3) | 738 (87.6) | 321 (89.2) | <.001 | 4537 (88.0) | 693 (87.2) | 3239 (84.1) | <.001 |
| Statin | 2121 (80.1) | 692 (82.2) | 308 (85.6) | .03 | 4283 (83.1) | 683 (85.9) | 3121 (81.1) | .002 |
| Beta-blocker | 1254 (47.4) | 458 (54.4) | 185 (51.4) | .001 | 2980 (57.8) | 419 (52.7) | 1897 (49.3) | <.001 |
| Antiplatelet medication | 1879 (70.9) | 644 (76.5) | 286 (79.4) | <.001 | 4061 (78.7) | 638 (80.3) | 2809 (72.9) | <.001 |
| Anticoagulant | 320 (12.1) | 112 (13.3) | 50 (13.9) | .46 | 562 (10.9) | 116 (14.6) | 482 (12.5) | .003 |
| ACE-inhibitor | 1170 (44.2) | 415 (49.3) | 183 (50.8) | .005 | 2731 (53.0) | 432 (54.3) | 1768 (45.9) | <.001 |
TIA, transient ischemic attack; IQR, interquartile range; BMI, body Mass Index; COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate. Variables are presented as numbers (%).
Recently symptomatic patients – stroke vs. hemispheric TIA vs. ocular TIA
In the recently symptomatic patient cohort, patient characteristics differed between stroke vs. hemispheric TIA vs. ocular TIA in age (69 years vs. 72 years vs. 68 years; P<.001), proportion of non-white patients (11.0% vs. 7.7% vs. 4.5%; P<.001), and proportion of female patients (35.1% vs. 38.7% vs. 30.0%; P = .01; Table I). Furthermore, there were differences in patient characteristics in the recently symptomatic patient cohort in active smoking status (32.8% vs. 25.2% vs. 33.1%; P<.001), proportion of patients with COPD (23.7% vs. 27.4% vs. 32.5%; P<.001), and proportion of patients with coronary artery disease (34.9% vs. 43.7% vs. 43.1%; P<.001). There were comparable proportions of patients with congestive heart failure or hypertension in the recently symptomatic patient cohort.
Recently symptomatic vs. formerly symptomatic vs. asymptomatic
Patient characteristics between recently symptomatic (ie. combining patients with recent stroke, recent ocular TIA, and recent hemispheric TIA) vs. formerly symptomatic vs. asymptomatic, were different in proportion of non-white race (9.7% vs. 6.6% vs. 6.5%; P<.001) and active smoking status (31.2% vs. 26.5% vs. 23.6%; P<.001; Table I). Furthermore, there was a difference between the study groups regarding hypertension (86.8% vs. 90.6% vs. 89.6%; P<.001) and coronary artery disease (37.6% vs. 46.8% vs. 48.1%; P<.001), while proportions of female sex, any diabetes, and congestive heart failure were comparable.
Outcomes
Recent stroke vs. hemispheric TIA
The stroke/death rate was higher in patients with a recent stroke compared with patients with a recent hemispheric TIA (5.5% vs. 2.4%; P<.001; Table II). Furthermore, recent stroke patients had higher rates of stroke (3.6% vs. 1.8%; P = .009), death (2.6% vs. 0.7%; P = .001), and prolonged LOS (40.2% vs. 20.5%; P<.001) compared with patients with recent hemispheric TIA. There were no differences in MI between recent stroke and recent hemispheric TIA patients.
Table II:
Unadjusted in-hospital outcomes after transfemoral carotid artery stenting stratified by specific pre-procedural symptom status
| 1. Stroke | 2. Hemispheric TIA | P-value 1 vs. 2 | 3. Ocular TIA | P-value 3 vs. 1 | P-value 3 vs. 2 | P-value 1 vs. 2 vs. 3 | 4. Asymptomatic | P-value 4 vs. 2 | P-value 4 vs. 3 | |
|---|---|---|---|---|---|---|---|---|---|---|
| In-hospital outcomes | ||||||||||
| N | 2650 | 842 | 360 | 5160 | ||||||
| Stroke or death | 145 (5.5) | 20 (2.4) | <.001 | 10 (2.8) | .03 | .68 | <.001 | 73 (1.4) | .04 | .04 |
| Stroke | 95 (3.6) | 15 (1.8) | .009 | 9 (2.5) | .29 | .42 | .02 | 54 (1.0) | .06 | .01 |
| Mortality | 68 (2.6) | 6 (0.7) | .001 | 2 (0.6) | .02 | .76 | <.001 | 21 (0.4) | .22 | .67 |
| MI | 25 (0. 9) | 5 (0.6) | .34 | 2 (0.6) | .46 | .94 | .52 | 21 (0.4) | .44 | .67 |
| LOS > 2 days | 1066 (40.2) | 173 (20.5) | <.001 | 40 (11.1) | <.001 | <.001 | <.001 | 580 (11.2) | <.001 | .94 |
TIA, transient ischemic attack; MI, myocardial infarction; LOS, hospital length of stay. Values are presented as numbers (%).
Recent stroke or hemispheric TIA vs. ocular TIA
Patients with recent stroke had a higher stroke/death rate compared with patients with recent ocular TIA (5.5% vs. 2.8%; P = .03; Table II). Patients with recent stroke furthermore had higher rates of death (2.6% vs. 0.6%; P = .02) and prolonged LOS (40.2% vs. 11.1%; P<.001) compared with patients with recent ocular TIA. There were no significant differences in stroke or MI occurrence between patients with recent stroke and ocular TIA.
The stroke/death rate was similar between recent hemispheric TIA vs. recent ocular TIA patients (2.4% vs. 2.8%; P = .68). However, patients with recent hemispheric TIA had a higher rate of prolonged LOS compared with patients with recent ocular TIA (20.5% vs. 11.1%; P<.001). The rates of stroke, death, or MI were similar between recent hemispheric vs. recent ocular TIA patients.
Recent hemispheric or ocular TIA vs. asymptomatic
Recent hemispheric TIA patients had a higher stroke/death rate compared with asymptomatic patients (2.4% vs. 1.4%; P = .04; Table II). Furthermore, prolonged LOS rates were higher in patients with hemispheric TIA compared with asymptomatic patients (20.5% vs. 11.2%; P<.001). There were no significant differences in rates of stroke, death, or MI, between hemispheric TIA and asymptomatic patients.
The stroke/death rate was higher in recent ocular TIA patients compared with asymptomatic patients (2.8% vs. 1.4%; P = .04). In addition, patients with recent ocular TIA had a higher stroke rate compared with asymptomatic patients (2.5% vs. 1.0%; P = .01). Other outcomes, including death, MI, and prolonged LOS were similar between ocular TIA and asymptomatic patients.
Formerly symptomatic vs. recently symptomatic or asymptomatic
There was no significant difference in stroke/death rate between formerly symptomatic vs. recently symptomatic patients (3.5% vs. 4.5%; P = .20; Table III). Formerly symptomatic patients had lower rates of death (0.5% vs. 2.0%; P = .004) and prolonged LOS (16.4% vs. 33.2%; P<.001) compared with recently symptomatic patients. There were no differences in rates of stroke or MI between formerly symptomatic and recently symptomatic patients.
Table III:
Unadjusted in-hospital outcomes after transfemoral carotid artery stenting stratified by pre-procedural symptom status
| In-hospital outcomes | 1. Asymptomatic | 2. Formerly Symptomatic | P-value 1 vs. 2 | 3. Recently Symptomatic | P-value 2 vs. 3 |
|---|---|---|---|---|---|
| N | 5160 | 795 | 3852 | ||
| Stroke or death | 73 (1.4) | 28 (3.5) | <.001 | 175 (4.5) | .20 |
| Stroke | 54 (1.0) | 25 (3.1) | <.001 | 119 (3.1) | .94 |
| Mortality | 21 (0.4) | 4 (0.5) | .70 | 76 (2.0) | .004 |
| MI | 21 (0.4) | 6 (0.8) | .17 | 32 (0.8) | .83 |
| LOS > 2 days | 580 (11.2) | 130 (16.4) | <.001 | 1279 (33.2) | <.001 |
MI, myocardial infarction; LOS, hospital length of stay. Values are presented as numbers (%).
Formerly symptomatic patients had a higher stroke/death rate compared with asymptomatic patients (3.5% vs. 1.4%; P<.001). In addition, formerly symptomatic patients had higher rates of stroke (3.1% vs. 1.0%; P<.001) and prolonged LOS (16.4% vs. 11.2%; P<.001) compared with asymptomatic patients. Between formerly symptomatic and asymptomatic patients there were no differences in death or MI rate.
Formerly symptomatic vs. recently symptomatic – stratified by specific pre-procedural symptoms
When comparing formerly with recently symptomatic patients stratified by specific pre-procedural symptoms, the proportions of patients with prior stroke, prior hemispheric TIA, or prior ocular TIA did not differ between both cohorts (Table IV).
Table IV:
Univariate analysis of formerly and recently symptomatic patient cohorts stratified by specific pre-procedural symptom status
| Formerly Symptomatic | Recently Symptomatic | P-value | |
|---|---|---|---|
| N | 795 | 3852 | |
| Prior stroke | 550 (69.2) | 2650 (68.8) | .83 |
| Prior hemispheric TIA | 179 (22.5) | 842 (21.9) | .68 |
| Prior ocular TIA | 66 (8.3) | 360 (9.3) | .35 |
TIA, transient ischemic attack. Values are presented as numbers (%).
Formerly symptomatic patients with prior stroke trended towards a lower stroke/death rate when compared with recently symptomatic patients with prior stroke (3.5% vs. 5.5%; P = .05; Table V). Stroke/death rates between formerly and recently symptomatic patients with prior hemispheric or ocular TIA were similar.
Table V:
Unadjusted in-hospital stroke/death rates after transfemoral carotid artery stenting in the formerly and recently symptomatic patient cohorts stratified by specific pre-procedural symptom status
| Formerly Symptomatic | Recently Symptomatic | P-value | |
|---|---|---|---|
| Prior stroke | 19 (3.5) | 145 (5.5) | .05 |
| Prior hemispheric TIA | 6 (3.4) | 20 (2.4) | .45 |
| Prior ocular TIA | 3 (4.5) | 10 (2.8) | .44 |
TIA, transient ischemic attack. Values are presented as numbers (%).
Multivariable analysis
After adjustment for covariables, compared with recent hemispheric TIA, the odds of stroke/death were two-fold higher with recent stroke (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.6–4.3; P<.001; Table VI). Compared with recent ocular TIA, recent stroke demonstrated a trend towards higher stroke/death (OR 2.0; 95% CI 1.0–3.9; P = .06), while recent hemispheric TIA was not associated with higher odds of stroke/death (OR 0.8; 95% CI 0.3–1.7; P = .50).
Table VI:
Association between pre-procedural symptom status and in-hospital stroke or death after transfemoral carotid artery stenting with different reference points
| OR | 95% CI | P-value | |
|---|---|---|---|
| Asymptomatic | Reference | ||
| Ocular TIA | 2.1 | 1.0 – 4.2 | .04 |
| Hemispheric TIA | 1.6 | 0.9 – 2.7 | .09 |
| Stroke | 4.1 | 3.0 – 5.6 | <.001 |
| Asymptomatic | 0.5 | 0.2 – 1.0 | .04 |
| Ocular TIA | Reference | ||
| Hemispheric TIA | 0.8 | 0.3 – 1.7 | .50 |
| Stroke | 2.0 | 1.0 – 3.9 | .06 |
| Asymptomatic | 0.6 | 0.4 – 1.1 | .09 |
| Ocular TIA | 1.3 | 0.6 – 3.0 | .50 |
| Hemispheric TIA | Reference | ||
| Stroke | 2.6 | 1.6 – 4.3 | <.001 |
OR, odds ratio; CI, confidence interval; TIA, transient ischemic attack.
Adjusted for: age, sex, race, hypertension, current smoking status, any diabetes mellitus, congestive heart failure, coronary artery disease, COPD, dialysis status, eGFR < 30 mL/min.
Compared with asymptomatic status, the odds of stroke/death were four-fold higher with recent stroke (OR 4.1; 95% CI 3.0–5.6; P<.001) and two-fold higher with recent ocular TIA (OR 2.1; 95% CI 1.0–4.2; P = .04). Compared with an asymptomatic status, recent hemispheric TIA demonstrated a trend towards higher stroke/death (OR 1.6; 95% CI 0.9–2.7; P = .09).
Compared with formerly symptomatic status, asymptomatic status was associated with lower odds of stroke/death (OR: 0.4; 95% CI: 0.2–0.6; P<.001; Table VII). However, compared with formerly symptomatic status, the odds of stroke/death with a recently symptomatic status (ie. combining recent stroke, hemispheric TIA, and ocular TIA) was similar (OR: 1.2; 95% CI: 0.8–1.9; P = .31).
Table VII:
Association between formerly symptomatic, asymptomatic, and recently symptomatic status and in-hospital stroke or death after transfemoral carotid artery stenting
| OR | 95% CI | P-value | |
|---|---|---|---|
| Formerly Symptomatic | Reference | ||
| Asymptomatic | 0.4 | 0.2 – 0.6 | <.001 |
| Recently Symptomatic | 1.2 | 0.8 – 1.9 | .31 |
OR, odds ratio; CI, confidence interval.
Adjusted for: age, sex, race, hypertension, current smoking status, any diabetes mellitus, congestive heart failure, coronary artery disease, COPD, dialysis status, eGFR < 30 mL/min.
DISCUSSION
In this contemporary analysis of TFCAS, we demonstrated distinct outcomes based on specific pre-procedural symptom status. After adjustment, recent stroke was associated with higher odds of stroke/death compared with asymptomatic status, or recent hemispheric TIA, while recent stroke demonstrated a trend towards higher stroke/death association compared with recent ocular TIA. Furthermore, a formerly symptomatic status was associated with higher odds of stroke/death compared with an asymptomatic status.
Within the recently symptomatic patient cohort, we found that recent stroke was associated with two-fold higher odds of stroke/death compared with recent hemispheric TIA, while recent stroke demonstrated a trend towards two-fold higher odds of stroke/death compared with recent ocular TIA. Moreover, we found that recent hemispheric TIA was associated with similar odds of stroke/death compared with recent ocular TIA. Our findings deviate from findings in a previous review of the Society for Vascular Surgery (SVS) Vascular Registry investigating 30-day outcomes in the early experience of TFCAS. In that review a similar stroke/death association was demonstrated between recent stroke compared with recent hemispheric TIA (OR: 1.2; 95% CI: 0.7–1.9; P = .55), while recent stroke had a three-fold higher odds of stroke/death compared with recent ocular TIA (OR: 2.9; 95% CI: 1.2–7.1; P = .02).3 Despite the distinct findings, significantly different outcomes within the recently symptomatic patient cohort have been demonstrated both in our study as well as in the previous review. This supports further stratification based on specific pre-procedural symptom status in preoperative risk-assessment.
We found that formerly symptomatic status (symptoms <180 days prior to the procedure) was associated with higher odds of stroke/death compared with asymptomatic status. The stroke/death rate of 3.5% that we observed in formerly symptomatic patients after TFCAS, was twice as high as the stroke/death rate in asymptomatic patients, while the stroke/death rate in formerly symptomatic patients was similar compared with stroke/death in recently symptomatic patients. Our findings differ from findings in a subgroup analysis of the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), which investigated 30-day stroke/death rates after TFCAS.9 The subgroup analysis demonstrated similar stroke/death association between asymptomatic and formerly symptomatic status (HR: 1.2; 95% CI: 0.2–9.0; P = .88).9 However, out of the 594 included patients in that analysis, only 36 patients were formerly symptomatic with 1 event within the formerly symptomatic cohort, which is reflected in the wide confidence interval. As in CREST, CREST-2, which is an ongoing trial investigating outcomes in asymptomatic patients after TFCAS or CEA, also does not distinguish between outcomes in formerly symptomatic and asymptomatic patients.11 However, our findings demonstrate that including formerly symptomatic patients in the asymptomatic cohort may lead to overestimation of adverse outcome rates in asymptomatic patients. Hence, our findings suggest that differentiating between formerly symptomatic patients and asymptomatic patients would allow for greater accuracy in outcome reporting in future studies.
The most recent SVS, American Heart Association (AHA), and European Society for Vascular Surgery (ESVS) guidelines for management of carotid disease do not make distinctions within the symptomatic patient cohort in their recommendations.12–14 With a low level of evidence, the SVS guidelines recommend TFCAS over CEA in symptomatic patients with stenosis >50% and who satisfy certain anatomic and medical characteristics.12 The AHA guidelines recommend an anticipated perioperative stroke/death rate of <6% in symptomatic patients to ensure benefit after TFCAS.13 With a lower level of evidence, the ESVS guidelines recommend that TFCAS may be considered as an alternative to CEA in recently symptomatic patients aged <70 years as long as the documented perioperative stroke/death rate is <6%.14 Patients with recent stroke in our study had an in-hospital stroke/death rate of 5.5%. While we were unable to accurately investigate post-discharge outcomes in this study, we previously found that half of all 30-day stroke/deaths in symptomatic patients following carotid artery stenting happen after discharge.15 This raises the question whether patients with recent stroke meet guideline recommendations for patient selection for TFCAS and further stresses the need for specific stratification in pre-operative risk assessment.
While the SVS guidelines do not recommend TFCAS for asymptomatic patients,12 the ESVS guidelines recommend a perioperative stroke/death rate of <3% to consider TFCAS as an alternative treatment for asymptomatic patients.14 The in-hospital stroke/death rate of 3.5% that we found in formerly symptomatic patients would certainly disqualify this patient cohort for treatment with TFCAS and supports stratification between asymptomatic and formerly symptomatic patients in future guideline recommendations. Evidence suggests that a history of prior infarction increases the risk of future stroke, which could support carotid intervention within this patient cohort.14 However, further research is needed to weigh the risks of treatment with modern medical management or CEA in formerly symptomatic patients.
The etiology of the different stroke/death rates between the distinct pre-procedural symptom statuses is a complex one. Plaque morphology could be a component in the differences in stroke/death rates based on symptom status. Vulnerable atherosclerotic plaque characteristics, which have been proven to correlate with higher rates of stroke,16 are more prevalent in patients with prior hemispheric TIA or prior stroke.17 Asymptomatic stenosis and prior ocular TIA, however, are associated with stable plaque morphology and thus lower complication rates.17 Although varying amounts of vulnerable plaque features and different pathological mechanisms between symptomatic patients likely are elements in distinct outcomes among recently symptomatic patients, other factors may play a role as well.18,19
TFCAS was established as a minimally invasive alternative to CEA in patients at high risk for surgery. However, due to higher association of postoperative stroke after TFCAS when compared with CEA and limited CMS reimbursement of TFCAS, CEA remains the prime carotid revascularization method.20–22 In recent years, transcarotid artery revascularization (TCAR) has been introduced as a novel carotid stenting procedure. With TCAR the carotid artery is entered at the base of the neck. In order to reduce embolization risk, with TCAR flow reversal is applied before crossing the lesion, whereas with TFCAS the lesion is crossed first before applying an embolic filter. Studies have shown that TCAR is associated with a lower risk of stroke/death when compared with TFCAS.23 Furthermore, a systematic review reported similar perioperative stroke/death rates after TCAR when compared with CEA, although the review also stresses the fact that larger prospective studies are needed to draw firmer conclusions.24 The introduction of TCAR might provide the option of minimally invasive carotid revascularization in patient cohorts who have characteristics which might limit them for treatment with TFCAS. One such potentially limiting factor is advanced age. In addition to the anticipated stroke/death rate, the ESVS guidelines recommend that TFCAS may be considered in patients who are <70 years.14 As a recent study reported similar in-hospital stroke/death rates after TCAR when compared with CEA, elderly patients might become eligible for treatment with carotid stenting through TCAR.25 Although novel, TCAR has shown to be a promising carotid revascularization option and the range of its application possibilities will become clearer in the near future.
As this study was a retrospective review of prospectively collected data, limitations that come with large clinical registries have to be considered, including errors in data entry and missing data. To reduce such potential limitations, VQI conducts annual audits to review the clinical data submitted from the hospitals.26 Some endpoints had low event rates which may have led to unexpected outcomes or lack of statistical power. The stroke/death rate was 2.4% in recent hemispheric TIA patients and 2.8% in recent ocular TIA patients (P = .68). Although not significantly different, previous studies have shown that ocular TIA is more benign than hemispheric TIA for presenting symptom.3,4 Furthermore, when comparing outcomes between recent hemispheric TIA and asymptomatic patients, stroke alone was close to significant. Death alone was not close to significant as there were very few deaths, but the trend was in the correct direction. However, event rates in stroke/death combined were much higher than either endpoint alone, so there was adequate statistical power to demonstrate a difference. The limited investigation of post-discharge outcomes was primarily due to the presence of missing data in long-term follow-up within the VQI registry. In a recent comparison of in-hospital and perioperative post-discharge adverse events however, we demonstrated that 47% of stroke/deaths occurred after discharge in symptomatic patients and 27% occurred after discharge in asymptomatic patients.15 It is unknown however what the proportion of perioperative post-discharge adverse events is when stratified by specific pre-procedural symptom status. This question should be addressed in a future study. Nonetheless, this study provides a contemporary view, with a larger sample, of in-hospital outcomes after TFCAS, stratified by specific pre-procedural symptom status.
Conclusion
Within the symptomatic patient cohort undergoing TFCAS, stroke/death rates are higher in patients with recent stroke compared with patients with recent ocular or hemispheric TIA. In addition, formerly symptomatic patients, which are often considered as asymptomatic, have higher rates of stroke/death compared with asymptomatic patients. These findings support further stratification based on specific pre-procedural symptom status and distinction between formerly symptomatic and asymptomatic patients, to improve pre-operative risk assessment and improve accuracy of future studies.
ARTICLE HIGHLIGHTS.
Type of research:
Retrospective review of prospectively collected Vascular Quality Initiative data.
Key Findings:
After carotid artery stenting, in-hospital stroke/death rates in patients with recent stroke (5.5%) were higher than in patients with recent hemispheric transient ischemic attack (TIA; 2.4%) or recent ocular TIA (2.8%). Moreover, the stroke/death rate was lower in asymptomatic patients (1.4%) compared with formerly symptomatic patients (3.5%).
Take Home Message:
These findings support further stratification based on specific pre-procedural symptoms and distinction between asymptomatic and formerly (>180 days) symptomatic patients undergoing transfemoral carotid artery stenting, to improve pre-operative risk assessment and increased accuracy in future studies.
Acknowledgments
PL is supported by the Harvard-Longwood Research Training in Vascular Surgery NIH T32 Grant 2T32HL007734
Footnotes
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