Annals of Vascular Surgery
Volume 23, Issue 5 , Pages 612-615, September 2009

Safety of Carotid Endarterectomy in Patients Concurrently on Clopidogrel

Department of Surgery, Mayo Clinic, Phoenix, AZ

Article Outline

Background

Clopidogrel (Plavix®) usage is increasing, primarily for the management of patients with cerebrovascular symptoms and for those receiving drug-eluting coronary artery stents. A significant percentage of these patients will require carotid endarterectomy (CEA) while they are receiving clopidogrel. Recent data have demonstrated an increased incidence of coronary stent thrombosis when clopidogrel is discontinued. The objective of this study was to determine if CEA could be performed safely while patients are continued on clopidogrel therapy.

Methods

A retrospective cohort design was employed to review consecutive patients who underwent CEA over a 24-month period ending March 2007. Patients were divided into two groups based on the perioperative use of clopidogrel. Preoperative demographics and postoperative results were compared between the two groups and statistically analyzed.

Results

Of the 100 patients who underwent CEA, 19 were taking clopidogrel within 5 days of surgery. This comprised the study group. The control group consisted of the 81 patients who did not receive clopidogrel. Heparin anticoagulation was routinely utilized prior to clamping in both groups. Demographics were similar between the groups. There were no statistical differences in morbidity or mortality between the control group and the clopidogrel group. Combined stroke/death rates were equivalent between the two groups (1.2% control vs. 0% clopidogrel). One hematoma developed in the control group, which did not require operative intervention.

Conclusion

In this series, our results suggest that patients concurrently on clopidogrel can safely undergo CEA without increased risk of hematoma or neurological complications. In view of recent data demonstrating adverse outcomes in patients discontinuing clopidogrel, this study is useful in optimally managing this group of patients.

 

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Introduction 

Since clopidogrel (Plavix®) was first approved for use by the Food and Drug Administration (FDA) in November 1997, there has been controversy regarding the performance of invasive procedures on patients concurrently taking this potent antiplatelet agent. As the FDA has approved its use for additional indications, it is now more frequently encountered in the hospital and outpatient environment. The current FDA-approved indications include acute coronary syndrome, recent myocardial infarction (MI), recent stroke, and established peripheral arterial disease.1 Clopidogrel is also frequently utilized for other off-label indications, such as thrombotic prophylaxis following percutaneous coronary or peripheral vascular interventions as well as in the management of venous stasis ulceration.2 There have been several reports in the literature associating higher postoperative bleeding and transfusion requirements in patients on clopidogrel undergoing cardiac surgery.3, 4, 5, 6 Currently, there are no reports describing the safety of clopidogrel usage in patients undergoing carotid endarterectomy (CEA). With FDA approval for use in patients with “recent stroke,” the utilization of clopidogrel has created a more frequently encountered quandary facing vascular surgeons in practice. Single-dose clopidogrel in combination with aspirin administration the night prior to CEA has been shown to significantly reduce postoperative thromboembolic potential without increasing the risk of bleeding complications.7 While single-dose use has demonstrated safety, concomitant therapy has yet to be proven prudent. Conversely, there have been case reports as well as a large retrospective cohort study suggesting detrimental effects of discontinuing clopidogrel.8 In addition, the 2007 guidelines published by the American College of Cardiology and American Heart Association recommend continuing clopidogrel for at least 12 months after placement of a drug-eluting stent.9 This further complicates the decision process regarding the continuation of clopidogrel during the need for open surgical intervention.

The goal of this analysis was to establish the safety of open carotid revascularization with concurrent use of clopidogrel.

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Methods 

A retrospective cohort design was employed to analyze consecutive patients who underwent a CEA between April 2005 and March 2007 at a tertiary-care university-affiliated institution. Approval for the study was obtained from the institutional review board. There were no patients undergoing CEA at our institution who were excluded from our review. All patients not taking clopidogrel within the 5 days prior to surgery were placed in the control group. All patients who had taken clopidogrel within 5 days prior to surgery were placed in the clopidogrel group. All operations were performed under general endotracheal anesthesia. The operative approach was at the surgeon's discretion. Oxidized regenerated cellulose (Surgicel Fibrillar®; Ethicon, Somerville, NJ) was routinely used in both groups. Dacron patch angioplasty was performed in 18 of the clopidogrel patients, with one patient undergoing a primary repair. Drain use was at the surgeon's discretion; a drain was used in two of the 19 patients in the clopidogrel group. Preoperative characteristics including age, presence or absence of symptoms, severity of carotid stenosis, and time since last clopidogrel dose were analyzed. Perioperative protamine use, estimated blood loss during surgery, and postoperative complications including transient ischemic attack (TIA), MI, stroke, hematoma, infection, and 30-day mortality were reviewed. The presence of hematoma was defined by any reference in the medical record by physician documentation of “hematoma.” This included small insignificant hematomas not requiring surgical management as well as large hematomas requiring surgical evacuation.

Data were analyzed using JMP version 6.0 (SAS Institute, Cary, NC), and summary statistics are presented as number (percentage) for categorical variables and mean ± standard deviation (SD) for continuous variables. Groups were compared using Fisher's exact tests for categorical variables and Wilcoxon's rank sum tests for continuous variables. All tests were two-tailed, and p<0.05 was considered statistically significantly.

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Results 

The medical records of 100 consecutive patients who underwent CEA at our institution between March 2005 and March 2007 were retrospectively reviewed. No patients were excluded from our review. Of those patients undergoing CEA, 81 had not received clopidogrel within 5 days of CEA, while 19 had received clopidogrel within 5 days of surgery. The indication for clopidogrel could be determined in 13 of the 19 patients and inferred in the remaining six patients, with cerebrovascular disease in 13, coronary stents in three, severe coronary artery disease in two, and infrainguinal disease in one. All patients in the clopidogrel group were on a regimen of 75mg/day. The mean number of days off (missed doses) of clopidogrel in the clopidogrel group was 1.66 (range 0-4). Furthermore, 13 of the 19 patients (68%) in the clopidogrel group were on dual antiplatelet therapy with both aspirin and clopidogrel. Nine of these patients (69%) were taking 81mg/day of aspirin, while four patients (31%) were taking 325mg/day of aspirin. The control and clopidogrel groups were demographically similar, with no significant differences in age, weight, degree of carotid stenosis, or presence of preoperative symptoms (see Table I). The two groups had statistically similar perioperative and postoperative hospital courses, including dose of intraoperative heparin, dose of intraoperative protamine, estimated blood loss, and length of hospitalization following surgery.

Table I. Preoperative demographics
Control groupClopidogrel groupp
n8119
Age (mean±SD)73.0±8.876.4±6.50.20
Weight (mean, kg)8184
Stenosis on MRA (mean)80%79.33%0.75
Stenosis on CTA (mean)78.3%78.8%0.90
Symptomatic lesions41 (50.6%)10 (52.6%)1.00

MRA, magnetic resonance angiography; CTA, computed tomography angiography.

Table II summarizes the primary end points of this study. There was no statistically significant difference in the rate of postoperative cerebrovascular events including stroke and TIA. One small postoperative hematoma occurred in the control group, while there were no postoperative hematomas in the clopidogrel group. The patient with the hematoma in the control group did not require operative intervention. The combined stroke/death rate was equivalent in the control and clopidogrel groups (1.2% and 0%, respectively). One postoperative MI occurred in the clopidogrel group, while there was one death in the control group secondary to aspiration pneumonia. There were no statistically significant differences in morbidity or mortality between the control and clopidogrel groups.

Table II. Summary of primary end point results for control and clopidogrel groups
Control groupClopidogrel groupp
n8119
Stroke0 (0%)0(0%)1.00
TIA2 (2.5%)1 (5%)0.47
Hematoma1 (1.2%)0 (0%)1.00
MI0 (0%)1 (5%)0.19
30-day mortality1 (1.2%)0 (0%)1.00
Estimated blood loss (mean±SD)98 ±61122 ±850.31

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Discussion 

In this study of 100 consecutive patients undergoing CEA, there was no evidence of increased morbidity or mortality associated with the perioperative use of clopidogrel. The incidence of hematoma formation following CEA has been reported at 7.1% in the North American Symptomatic Carotid Endarterectomy Trial (NASCET).10 Other studies have reported a hematoma rate between 1.2% and 12%.11, 12, 13, 14 The incidence of hematoma formation reported in the surgical literature is directly related to the definition of the presence of a hematoma. Many of the studies reported only hematomas that required surgical evacuation and, therefore, had small rates of hematoma formation. In our series, we anticipated having at least one patient with a postoperative hematoma in the clopidogrel group. However, none was identified in this retrospective review. It is important to compare equivalent definitions of hematoma presence. In our review, there were no patients in either the control or clopidogrel group who required surgical intervention for either evacuation of hematoma or bleeding following CEA. Our overall incidence of hematoma was 1%. This included one patient who had documentation of a hematoma but did not require operative intervention. Patients in the clopidogrel group had no documented hematomas, no bleeding complications, and no requirement of additional adjuncts to assure hemostasis prior to closure. Both groups routinely had application of oxidized regenerated cellulose (Surgicel Fibrillar) on the suture line and Dacron patch at the surgeon's discretion.

The most widely reviewed complication following CEA is stroke. The incidence in one large study (9,308 CEA patients) was 3.28%.13 The NASCET reported a stroke rate at 30 days of 2.9%.10 The Asymptomatic Carotid Atherosclerosis Study (ACAS) reported a 2.3% stroke or death rate in the perioperative period in 825 patients.15 The European Carotid Surgery trial reported a rate of major stroke or death complicating surgery of 7%.16 In contrast, the above studies did not specifically report the incidence of postoperative TIA. The incidence of perioperative TIAs in the control group was 2/81 (2.5%) and that in the clopidogrel group was 1/19 (5%). All patients with neurological symptoms underwent either magnetic resonance imaging (MRI) or computed tomography (CT). One patient in the control group with neurological symptoms did have subtle signal changes on MRI. All deficits from TIAs resolved within 24hr. None of these patients required reoperation. Although our series had no patients who sustained a postoperative stroke, a 1% risk of death was found. One patient in the control group died as a result of aspiration pneumonia, which was felt to have occurred on the induction of anesthesia. The patient did not exhibit any signs of stroke. The three patients in our series with postoperative pneumonia did not undergo neurological imaging. Patients in the clopidogrel group had no deaths or stroke.

The use of perioperative clopidogrel has been postulated to decrease the incidence of perioperative cerebrovascular events.7 In one study, a beneficial effect of a single preoperative dose of clopidogrel combined with aspirin was found in reducing cerebral emboli, determined by transcranial Doppler, in patients undergoing CEA.7 Fifty-eight of the 81 patients (72%) in the control group were taking aspirin preoperatively, with 13 patients (22%) taking 325mg/day and 45 patients (78%) taking 81mg/day. The mean time off of aspirin was 0.37 days. In addition, 13 of the 19 patients (68%) in the clopidogrel group were also taking aspirin, with four (31%) taking 325mg/day and nine (69%) taking 81mg/day. The mean time off of aspirin was 0.46 days in the clopidogrel group concurrently taking aspirin. With the addition of aspirin to clopidogrel we would have expected a higher bleeding risk from the additional platelet dysfunction, but again in our series we found no additional risk of complication.

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Conclusion 

Overall, our study shows no statistical difference in bleeding complication, wound infection, stroke, or TIA in patients concurrently on clopidogrel who undergo CEA. These results suggest that patients concurrently on clopidogrel can safely undergo CEA without increased risk of hematoma or neurological complications. Given the limited number of patients in our review, a larger prospective randomized study is needed to demonstrate equivalent complication rates. However, we have concluded from our series that CEA can be performed safely in patients concurrently taking clopidogrel. In addition, the low stroke rate found in this study (0%) may be related to the preoperative use of aspirin and/or clopidogrel. Further investigation is needed to confirm this observation.

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References 

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PII: S0890-5096(09)00127-7

doi:10.1016/j.avsg.2009.06.004

Annals of Vascular Surgery
Volume 23, Issue 5 , Pages 612-615, September 2009

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