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Gender-specific 30-day outcomes after carotid endarterectomy and carotid artery stenting in the Society for Vascular Surgery Vascular Registry

Open ArchivePublished:November 18, 2013DOI:https://doi.org/10.1016/j.jvs.2013.09.036

      Objective

      Although the optimal treatment of carotid stenosis remains unclear, available data suggest that women have higher risk of adverse events after carotid revascularization. We used data from the Society for Vascular Surgery Vascular Registry to determine the effect of gender on outcomes after carotid endarterectomy (CEA) and carotid artery stenting (CAS).

      Methods

      There were 9865 patients (40.6% women) who underwent CEA (n = 6492) and CAS (n = 3373). The primary end point was a composite of death, stroke, and myocardial infarction at 30 days.

      Results

      There was no difference in age and ethnicity between genders, but men were more likely to be symptomatic (41.6% vs 38.6%; P < .003). There was a higher prevalence of hypertension and chronic obstructive pulmonary disease in women, whereas men had a higher prevalence of coronary artery disease, history of myocardial infarction, and smoking history. For disease etiology in CAS, restenosis was more common in women (28.7% vs 19.7%; P < .0001), and radiation was higher in men (6.2% vs 2.6%; P < .0001). Comparing by gender, there were no statistically significant differences in the primary end point for CEA (women, 4.07%; men, 4.06%) or CAS (women, 6.69%; men, 6.80%). There remains no difference after stratification by symptomatology and multivariate risk adjustment.

      Conclusions

      In this large, real-world analysis, women and men demonstrated similar results after CEA or CAS. These data suggest that, contrary to previous reports, women do not have a higher risk of adverse events after carotid revascularization.
      Cerebrovascular disease is a leading cause of death and the leading cause of serious long-term disability in the United States.
      • Hoyert D.L.
      • Xu J.
      Division of vital statistics: death: preliminary data for 2011.
      • Go A.S.
      • Mozaffarian D.
      • Roger V.L.
      • Benjamin E.J.
      • Berry J.D.
      • Borden W.B.
      • et al.
      Heart disease and stroke statistics—2013 updates: a report from the American Heart Association.
      Carotid revascularization is an essential treatment option for select patients with significant internal carotid artery stenosis. Carotid endarterectomy (CEA) remains considered by many to be the gold standard procedure in carotid revascularization. The benefits of CEA over best medical therapy in subgroups of patients were demonstrated in several landmark randomized clinical trials during the past 2 decades.
      North American Symptomatic Carotid Endarterectomy Trial (NASCET) Investigators
      Benefit of carotid endarterectomy for patients with high-grade carotid stenosis.
      Executive Committee for the Asymptomatic Carotid Atherosclerosis Study
      Endarterectomy for asymptomatic carotid artery stenosis.
      European Carotid Surgery Trialist's Collaborative Group
      Randomized trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).
      MRC Asymptomatic Carotid Surgery Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      Since its introduction, carotid angioplasty and stenting (CAS) has been touted as an alternative to CEA.
      • Marks M.P.
      • Dake M.D.
      • Steinberg G.K.
      • Norbash A.M.
      • Lane B.
      Stent placement for artery and venous cerebrovascular disease: preliminary experience.
      • Yadav J.S.
      • Roubin G.S.
      • Iyer S.
      • Vitek J.
      • King P.
      • Jordan W.D.
      • et al.
      Elective stenting of the extracranial carotid arteries.
      Although the clinical efficacy and effectiveness of CAS compared with CEA remain debated, there is clear utility in patients with select high-risk criteria.
      • Gurm H.S.
      • Yadav J.S.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • Bajwa T.K.
      • et al.
      Long-term results of carotid stenting versus endarterectomy in high-risk patients.
      International Carotid Stenting Investigators
      Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomized controlled trial.
      • Brott T.G.
      • Hobson 2nd, R.W.
      • Howard G.
      • Roubin G.S.
      • Clark W.M.
      • Brooks W.
      CREST investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis.
      Gender plays an important role in cardiovascular disease. Epidemiologic studies have demonstrated that men have a higher incidence and prevalence rate of stroke than women.
      • Appelros P.
      • Stegmayr B.
      • Terent A.
      Sex differences in stroke epidemiology: a systematic review.
      The strokes that do occur in women tend to be more severe, however. In terms of revascularization, the available literature suggests that women have higher risk of perioperative adverse events.
      European Carotid Surgery Trialist's Collaborative Group
      Randomized trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).
      MRC Asymptomatic Carotid Surgery Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      This thus puts into question how much women actually benefit from carotid revascularization compared with men.
      The Society for Vascular Surgery (SVS) Vascular Registry (VR) on carotid procedures was developed to collect long-term outcomes on patients treated with CEA and CAS.
      • Sidawy A.N.
      • Zwolak R.M.
      • White R.A.
      • Siami F.S.
      • Schermerhorn M.L.
      • Sicard G.A.
      Outcomes Committee for the Society for Vascular Surgery. Risk-adjusted 30-day outcomes of carotid stenting and endarterectomy: results from the SVS Vascular Registry.
      As the first societal registry to enroll CEA and CAS patients, the VR is one of the largest published databases of carotid revascularization procedures in the United States. The purpose of this study was to use the SVS-VR to determine the effect of gender on outcomes after CEA and CAS.

      Methods

      VR data are reported by providers through Web-based electronic data capture. The measurement schedule includes baseline (preoperative) information, such as patient demographics, medical history, carotid symptom status, preprocedural diagnostic imaging, and laboratory values; procedural information, including procedural and predischarge complications; and follow-up information such as postprocedure mortality, stroke, myocardial infarction (MI), and other morbidity. All data entered into the VR are fully compliant with the Health Insurance Portability and Accountability Act regulations and are auditable. All data reports and analyses performed included only deidentified and aggregated data. Additional details regarding the SVS-VR have been previously discussed.
      • Sidawy A.N.
      • Zwolak R.M.
      • White R.A.
      • Siami F.S.
      • Schermerhorn M.L.
      • Sicard G.A.
      Outcomes Committee for the Society for Vascular Surgery. Risk-adjusted 30-day outcomes of carotid stenting and endarterectomy: results from the SVS Vascular Registry.
      New England Research Institutes Inc (NERI, Watertown, Mass) maintains the online database. Funding for the administration and database management of the VR has been provided by the SVS (Chicago, Ill).

       Outcomes

      The primary outcome measure is a composite of the incidence of death, stroke, or MI. Stroke is defined as any nonconvulsive, focal neurologic deficit of abrupt onset persisting >24 hours. The ischemic event must correspond to a vascular territory. An MI is classified as:
      • A Q wave MI in which one of the following criteria is required: (1) chest pain or other acute symptoms consistent with myocardial ischemia and new pathologic Q waves in two or more contiguous electrocardiogram (ECG) leads; or (2) new pathologic Q waves in two or more contiguous ECG leads and elevation of cardiac enzymes; or
      • A non-Q wave MI, which is defined as creatinine kinase ratio >2 and creatinine kinase-myocardial band >1 in the absence of new, pathologic Q waves.
      Analysis of the 30-day outcomes was based on only those patients who had at least a 30-day follow-up visit (>16 days) or who experienced an end point (death, stroke, or MI) ≤30 days of treatment.

       Statistical methods

      Tests of statistical significance were conducted with χ2 or Fisher exact tests for categoric variables and t-tests for continuous variables. Descriptive statistics are listed as mean ± standard deviation for continuous variables and percentage (frequency) for categoric variables. Subset analyses were performed using the two-tailed t-test for continuous variables and the Fisher exact test for discrete and categoric data. Unadjusted and adjusted odds ratios (ORs) found through multivariate logistic regression were used to compare the primary outcomes across subgroups and are presented with 95% confidence intervals (CIs). ORs were adjusted for significant baseline factors that were retained after applying the backward elimination method. Differences were considered significant if P was < .05. All statistical analyses were performed by NERI using SAS statistical software (SAS Institute, Cary, NC).

      Results

      For the purpose of this study, the analysis was limited to patients treated for carotid disease caused by atherosclerosis, radiation, and restenosis. This led to an exclusion of 454 patients treated for alternative etiologies (eg, dissection, fibromuscular dysplasia, and trauma). There were 9865 patients who had 30-day follow-up data, with 40.6% women (n = 4008) and 59.4% men (n = 5857). For CEA (65.8%; n = 6492), there were 41.3% women (n = 2678) and 58.7% men (n = 3814). For CAS (34.2%; n = 3373), there were 39.4% women (n = 1330) and (60.6%) men (n = 2043). The characteristics of the two gender groups can be found in Table I. Men and women had a similar age and ethnicity profile. Women were more likely to be treated for restenosis (10.2% vs 7.8%) and less often for radiation-induced disease (0.9% vs 2.3%). Men were more likely to be treated for symptomatic disease (41.6% vs 38.6%). There was an equal prevalence (55%) of patients with at least one high-risk factor as defined by the Center for Medicare and Medicaid Services.
      Table IBaseline demographics, disease etiology, and medical history
      Variable
      Continuous variables are presented as mean (range) and categoric variables as percentage (number).
      Female (n = 4008)Male (n = 5857)P
      P value for age was found using the t-test. All others were found using the χ2 test.
      Age, years71.1 (18-95)70.9 (35-98).2874
      White—Caucasian92.4 (3705)92.8 (5434).5302
      Hispanic3.5 (139)3.4 (200).9104
      Etiology
       Atherosclerosis88.9 (3563)89.9 (5268)<.0001
       Radiation0.9 (37)2.3 (132)
       Restenosis10.2 (408)7.8 (457)
       Carotid symptomatology, % symptomatic38.6 (1547)41.6 (2439).0026
       Stroke21.6 (864)23.2 (1358).0589
       Transient ischemic attack20.4 (817)20.7 (1210).7608
       Transient monocular blindness5.5 (219)6.5 (379).0434
       Any high-risk factor
      High-risk factors, as defined by Center for Medicare and Medicaid Services, include age >80 years, New York Heart Association Congestive Heart Failure Class III/IV, ejection fraction <30%, unstable angina, myocardial infarction (MI) ≤30 days, restenosis, radical neck dissection, contralateral occlusion, prior radiation to neck, contralateral laryngeal nerve injury, and high anatomic lesion.
      54.7 (2192)55.4 (3245).4843
      a Continuous variables are presented as mean (range) and categoric variables as percentage (number).
      b P value for age was found using the t-test. All others were found using the χ2 test.
      c High-risk factors, as defined by Center for Medicare and Medicaid Services, include age >80 years, New York Heart Association Congestive Heart Failure Class III/IV, ejection fraction <30%, unstable angina, myocardial infarction (MI) ≤30 days, restenosis, radical neck dissection, contralateral occlusion, prior radiation to neck, contralateral laryngeal nerve injury, and high anatomic lesion.
      The patient characteristics after separation by procedure and gender can be found in Table II. For both procedures, the age and ethnicity distribution were similar. There was a low prevalence (<2%) of CEA patients treated for radiation or restenosis. Men were more likely to be symptomatic (39.2% vs 35.8%; P < .007), driven by a higher (22.2% vs 19.2%; P = .004) previous history of stroke. For CAS patients, women had a higher prevalence of restenosis (28.7% vs 19.7%), and men were more likely to be treated for radiation-induced disease (6.2% vs 2.6%). The distribution by medical history within the two procedures was similar. Men tended to have a higher prevalence of coronary artery disease and history of MI and tobacco use, whereas women had a higher prevalence of hypertension and chronic obstructive pulmonary disease. There was no difference in the use of antiplatelet therapy or the presence of Center for Medicare and Medicaid Services high-risk factors. The differences between the percentages of men and women with baseline ultrasound stenosis >80% or contralateral stenosis >70% were not statistically significant.
      Table IIBaseline demographics, disease etiology, medical history, and carotid evaluation—stratified by procedure
      Variable
      Continuous variables are presented as mean (range) and categoric variables as percentage (number).
      CEA patientsCAS patients
      Female (n = 2678)Male (n = 3814)P
      P value for age was found using the t-test. P value for etiology was found using the χ2 test. All others were found using the Fisher exact test.
      Female (n = 1330)Male (n = 2043)P
      P value for age was found using the t-test. P value for etiology was found using the χ2 test. All others were found using the Fisher exact test.
      Age, years71.0 (37-95)70.7 (35-98).229571.2 (18-94)71.2 (35-96).8184
      White—Caucasian92.5 (2477)93.0 (3546).465592.3 (1228)92.4 (1888).9471
      Hispanic3.0 (81)2.7 (102).40324.4 (58)4.8 (98).6149
      Etiology
       Atherosclerosis99.0 (2650)98.4 (3754).178768.6 (913)74.1 (1514)<.0001
       Radiation0.1 (2)0.2 (6)2.6 (35)6.2 (126)
       Restenosis1.0 (26)1.4 (54)28.7 (382)19.7 (403)
       Carotid symptomatology, % symptomatic35.8 (960)39.2 (1494).006944.1 (587)46.3 (945).2292
       Stroke19.2 (514)22.2 (845).004026.3 (350)25.1 (513).4431
       Transient ischemic attack19.1 (511)19.1 (729)>.999923.0 (306)23.5 (481).7390
       TMB4.9 (131)5.7 (217).16236.6 (88)7.9 (162).1585
      Medical history
       Coronary artery disease40.4 (1082)53.8 (2053)<.000151.8 (689)63.2 (1291)<.0001
       MI12.8 (344)18.9 (719)<.000120.1 (267)23.6 (482).0176
       Valvular heart disease8.8 (235)7.2 (276).02466.3 (84)6.0 (122).7131
       Cardiac arrhythmia11.2 (301)14.2 (540).000614.4 (191)15.0 (307).6196
       Congestive heart failure8.3 (221)7.6 (288).302615.0 (199)14.2 (290).5484
       Hypertension85.4 (2287)83.4 (3182).032086.8 (1155)81.1 (1657)<.0001
       Diabetes31.1 (833)31.8 (1212).568936.2 (481)34.2 (699).2523
       COPD18.9 (505)16.9 (645).044022.3 (296)19.3 (394).0401
       Chronic renal failure2.9 (79)3.7 (140).12443.4 (45)4.1 (84).3126
       Peripheral vascular disease44.8 (1199)42.2 (1611).044437.1 (494)37.2 (760)>.9999
       GI ulcer/bleeding3.6 (96)2.7 (102).03995.4 (72)4.4 (89).1610
       Current or past smoker56.8 (1521)63.4 (2419)<.000154.0 (718)65.8 (1344)<.0001
       Cancer12.3 (330)13.5 (514).177414.2 (189)23.0 (469)<.0001
       Coagulopathy1.2 (32)1.5 (58).28291.4 (19)0.7 (14).0472
       ASA grade <392.2 (2468)90.2 (3440).006390.7 (1206)92.8 (1896).0276
       NYHA scale <295.2 (2550)95.5 (3644).547488.9 (1182)88.5 (1809).7814
       Aspirin or clopidogrel87.1 (2333)88.1 (3359).250295.6 (1272)96.3 (1968).3205
       Any high-risk factor
      High-risk factors, as defined by Center for Medicare and Medicaid Services, include age >80 years, NYHA Congestive Heart Failure Class III/IV, ejection fraction <30%, unstable angina, MI ≤30 days, restenosis, radical neck dissection, contralateral occlusion, prior radiation to neck, contralateral laryngeal nerve injury, and high anatomic lesion.
      36.7 (984)36.5 (1394).872990.8 (1208)90.6 (1851).8260
      Carotid evaluation
       Baseline ultrasound imaging >80%68.8 (1717)70.5 (2500).154877.6 (923)77.5 (1362)>.9999
       Contralateral stenosis >70%18.1 (482)19.0 (722).363626.1 (342)24.1 (489).2190
      Stent information
       Use of embolic protection96.7 (1286)97.7 (1997).0797
       No. of stents, >18.3 (110)6.5 (133).0565
      ASA, American Society of Anesthesiologists; CAS, carotid artery stenting; CEA, carotid endarterectomy; COPD, chronic obstructive pulmonary disease; GI, gastrointestinal; MI, myocardial infarction; NYHA, New York Heart Association; TMB, transient monocular blindness.
      a Continuous variables are presented as mean (range) and categoric variables as percentage (number).
      b P value for age was found using the t-test. P value for etiology was found using the χ2 test. All others were found using the Fisher exact test.
      c High-risk factors, as defined by Center for Medicare and Medicaid Services, include age >80 years, NYHA Congestive Heart Failure Class III/IV, ejection fraction <30%, unstable angina, MI ≤30 days, restenosis, radical neck dissection, contralateral occlusion, prior radiation to neck, contralateral laryngeal nerve injury, and high anatomic lesion.

       CEA patients

      In patients undergoing CEA (Tables III and IV), there was no statistically significant difference in the 30-day outcomes. The primary end point was nearly identical (4.07% female and 4.06% male), as were the individual end points of mortality, stroke, or MI. Asymptomatic patients undergoing CEA had the lowest event rates, with the composite death/stroke/MI rate being 3.03% in women and 3.19% in men. The rate was higher in symptomatic patients, with the primary end point occurring in 5.94% women and 5.42% men. Even after risk adjustment (Table V), no difference remained (OR, 1.15; 95% CI, 0.89-1.48; P = .2958) between women and men undergoing CEA.
      Table IIIThirty-day outcomes for patients undergoing carotid endarterectomy (CEA)
      Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      30-day eventsCEA patients, % (No.)
      Female (n = 2678)Male (n = 3814)P
      P values were based on the Fisher exact test.
      Mortality0.86 (23)0.87 (33)>.9999
      Stroke2.58 (69)2.49 (95).8724
      MI1.16 (31)1.26 (48).7320
      Death, stroke, or MI4.07 (109)4.06 (155)>.9999
      MI, Myocardial infarction.
      a Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      b P values were based on the Fisher exact test.
      Table IVThirty-day outcomes for symptomatic and asymptomatic patients undergoing carotid endarterectomy (CEA)
      Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      30-day eventsAsymptomatic CEA, % (No.)Symptomatic CEA, % (No.)
      Female (n = 1718)Male (n = 2320)P
      P values were based on the Fisher exact test.
      Female (n = 960)Male (n = 1494)P
      P values were based on the Fisher exact test.
      Mortality0.64 (11)0.82 (19).58131.25 (12)0.94 (14).5453
      Stroke1.51 (26)1.68 (39).70624.48 (43)3.75 (56).4007
      MI1.28 (22)1.21 (28).88590.94 (9)1.34 (20).4462
      Death, stroke, or MI3.03 (52)3.19 (74).78455.94 (57)5.42 (81).5912
      MI, Myocardial infarction.
      a Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      b P values were based on the Fisher exact test.
      Table VUnadjusted and risk-adjusted odds ratios (ORs) for patients undergoing carotid endarterectomy (CEA)
      Adjusted ORs were calculated after adjusting for American Society of Anesthesiologist grade <3 vs >3, presence of coronary artery disease, aspirin use, ejection fraction <30%, and unstable angina.
      30-day death, stroke, or MIFemale vs male
      UnadjustedAdjusted
      OR (95% CI)P
      P values were based on the Fisher exact test.
      OR (95% CI)P
      P values were based on the Fisher exact test.
      All CEA1.00 (0.78-1.29).99001.15 (0.89-1.48).2958
      Asymptomatic CEA0.95 (0.66-1.36).76851.05 (0.73-1.52).7854
      Symptomatic CEA1.10 (0.78-1.56).58841.24 (0.87-1.78).2321
      CI, Confidence interval; MI, myocardial infarction.
      a Adjusted ORs were calculated after adjusting for American Society of Anesthesiologist grade <3 vs >3, presence of coronary artery disease, aspirin use, ejection fraction <30%, and unstable angina.
      b P values were based on the Fisher exact test.

       CAS patients

      In patients undergoing CAS (Tables VI and VII), there again was no statistically significant difference in outcomes in the two gender groups. The composite death/stroke/MI rates were 6.69% in women and 6.80% in men, higher than the 4% rate in CEA patients. In asymptomatic patients, the event rate was higher for women (5.79% vs 4.55%; P = .2353). There was also a higher rate of primary end point in symptomatic men (9.42% vs 7.84%; P = .3088) than women. However, neither of these reached statistical significance. After risk adjustment (Table VIII), no difference remained between women and men (OR, 0.91; 95% CI, 0.68-1.21; P = .5115).
      Table VIThirty-day outcomes for patients undergoing carotid angioplasty and stenting (CAS)
      Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      30-day eventsCAS patients, % (No.)
      Female (n = 1330)Male (n = 2043)P
      P values were based on the Fisher exact test.
      Mortality1.80 (24)1.86 (38)>.9999
      Stroke4.44 (59)4.99 (102).5087
      MI1.65 (22)1.08 (22).1634
      Death, stroke, or MI6.69 (89)6.80 (139).9441
      MI, Myocardial infarction.
      a Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      b P values were based on the Fisher exact test.
      Table VIIThirty-day outcomes for symptomatic and asymptomatic patients undergoing carotid angioplasty and stenting (CAS)
      Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      30-day eventsAsymptomatic CAS, % (No.)Symptomatic CAS, % (No.)
      Female (n = 743)Male (n = 1098)P
      P values were based on the Fisher exact test.
      Female (n = 587)Male (n = 945)P
      P values were based on the Fisher exact test.
      Mortality1.75 (13)1.18 (13).32111.87 (11)2.65 (25).3882
      Stroke3.90 (29)2.82 (31).22875.11 (30)7.51 (71).0719
      MI1.21 (9)1.09 (12).82602.21 (13)1.06 (10).0841
      Death, stroke, or MI5.79 (43)4.55 (50).23537.84 (46)9.42 (89).3088
      MI, Myocardial infarction.
      a Events were defined as any event occurring intraoperatively, before discharge, or between discharge and 30 days. Rates are per-patient.
      b P values were based on the Fisher exact test.
      Table VIIIUnadjusted and risk-adjusted odds ratios (ORs) for patients undergoing carotid angioplasty and stenting (CAS)
      Adjusted ORs were calculated after adjusting for American Society of Anesthesiologist grade <3 vs >3, etiology of restenosis, history of prior neck radiation, age >80 years, and number of stents (>1).
      30-day death, stroke, or MIFemale vs male
      UnadjustedAdjusted
      OR (95% CI)P
      P values were based on the Fisher exact test.
      OR (95% CI)P
      P values were based on the Fisher exact test.
      All CAS0.98 (0.75-1.29).89940.91 (0.68-1.21).5115
      Asymptomatic CAS1.29 (0.85-1.96).23671.23 (0.80-1.88).3538
      Symptomatic CAS0.82 (0.56-1.19).28910.72 (0.49-1.06).0964
      CI, Confidence interval; MI, myocardial infarction.
      a Adjusted ORs were calculated after adjusting for American Society of Anesthesiologist grade <3 vs >3, etiology of restenosis, history of prior neck radiation, age >80 years, and number of stents (>1).
      b P values were based on the Fisher exact test.

      Discussion

      Revascularization has become an important treatment option for patients with carotid artery occlusive disease. In two landmark randomized control trials in the 1990s, the benefits of CEA over medical therapy were demonstrated for patients with moderate or severe internal carotid artery stenosis.
      North American Symptomatic Carotid Endarterectomy Trial (NASCET) Investigators
      Benefit of carotid endarterectomy for patients with high-grade carotid stenosis.
      Executive Committee for the Asymptomatic Carotid Atherosclerosis Study
      Endarterectomy for asymptomatic carotid artery stenosis.
      Additional studies since have demonstrated the safety and efficacy of CAS as an alternative treatment option.
      • Gurm H.S.
      • Yadav J.S.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • Bajwa T.K.
      • et al.
      Long-term results of carotid stenting versus endarterectomy in high-risk patients.
      International Carotid Stenting Investigators
      Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomized controlled trial.
      • Brott T.G.
      • Hobson 2nd, R.W.
      • Howard G.
      • Roubin G.S.
      • Clark W.M.
      • Brooks W.
      CREST investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis.
      Despite these findings, the benefit of carotid revascularization in women remains unclear.
      The available literature suggests that women have a higher risk of perioperative adverse events during carotid revascularization. In the Asymptomatic Carotid Atherosclerosis Study (ACAS), women had a higher rate of perioperative events (3.6% vs 1.7% for men) during CEA.
      Executive Committee for the Asymptomatic Carotid Atherosclerosis Study
      Endarterectomy for asymptomatic carotid artery stenosis.
      Combining that with a lower rate of events for women (8.7% vs 12.1% for men) treated with best medical therapy, this led to a much lower 5-year risk reduction for women (17%) compared with men (66%). Among patients with moderate stenosis in the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the number needed to treat with CEA to prevent one ipsilateral stroke was 12 and the number needed to treat to prevent one disabling stroke was 16 for men. The corresponding numbers for women were 67 and 125, respectively, potentially suggesting a lower long-term benefit of surgery for women.
      North American Symptomatic Carotid Endarterectomy Trial (NASCET) Investigators
      Benefit of carotid endarterectomy for patients with high-grade carotid stenosis.
      The Asymptomatic Carotid Surgery Trial (ACST) produced similar findings, with men deriving a higher 5-year absolute risk reduction (8.21% vs 4.08%) than women.
      MRC Asymptomatic Carotid Surgery Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      The data are somewhat unclear in the recent trials evaluating CAS and CEA. Women in the International Carotid Stenting Study (ICSS) had a higher 120-day event rate for CEA (7.6% vs 4.2%) but a lower rate for CAS (8.0% vs 8.7%).
      International Carotid Stenting Investigators
      Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomized controlled trial.
      The opposite was found in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), with a lower periprocedural event rate for women undergoing CEA (3.8%) than men (4.9%) but higher in CAS (6.8% vs 4.3%).
      • Howard V.J.
      • Lutsep H.L.
      • Mackey A.
      • Demaerschalk B.M.
      • Sam 2nd, A.D.
      • Gonzales N.R.
      • et al.
      Influence of sex on outcomes of stenting versus endarterectomy: a subgroup analysis of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).
      With potentially higher perioperative event rates, these data raise the question of how much women actually benefit from intervention.
      Gender clearly plays an important role in cardiovascular disease. A systematic review of epidemiologic studies found the stroke incidence rate was 33% higher and stroke prevalence was 41% higher in men than in women.
      • Appelros P.
      • Stegmayr B.
      • Terent A.
      Sex differences in stroke epidemiology: a systematic review.
      When strokes do occur, they tended to be more severe in women, with a 1-month case fatality of 24.7% compared with 19.7% for men. However, the specific factors that lead to differential gender-specific outcomes remain unclear. Several factors (including vessel diameter, plaque morphology, influence of sex hormones and thromboembolic potential) have been proposed to play an important role. However, the overall evidence for outcome differences by gender-specific characteristics in the published literature remains limited.
      • den Hartog A.G.
      • Algra A.
      • Moll F.L.
      • de Borst G.J.
      Mechanisms of gender-related outcome differences after carotid endarterectomy.
      This study identified 9865 patients who underwent carotid revascularization in the SVS-VR. The 30-day outcomes in women compared with men were essentially the same. Both gender groups had a similar 30-day composite rate of death/stroke/MI: ∼4% for CEA and 7% for CAS. After stratifying by symptomatology, no differences remained in outcome. There are likely several reasons why the results from this study differ from the published clinical trial data. The SVS-VR was designed to capture real-world outcomes and is available to all clinical facilities and providers in the United States. As such, it represents more of the routine practice found in this country as opposed to the carefully defined patient selection criteria and practitioner credentialing that is seen in randomized clinical trials. This difference in outcomes for actual practice compared with clinical trials has been shown in the past for CEA and CAS.
      • Wennberg D.E.
      • Lucas F.L.
      • Birkmeyer J.D.
      • Bredenberg C.E.
      • Fisher E.S.
      Variations in carotid endarterectomy mortality in the Medicare population: trial hospitals, volume, and patient characteristics.
      • Yeh R.W.
      • Kennedy K.
      • Spertus J.A.
      • Parikh S.A.
      • Sakhuja R.
      • Anderson H.V.
      • et al.
      Do postmarketing surveillance studies represent real-world populations?: A comparison of patient characteristics and outcomes after carotid artery stenting.
      Another important distinguishing feature about this study is that data collection in the SVS-VR began in July 2005, almost 20 years after the first patient was enrolled in ACAS or NASCET. During the intervening two decades, best medical therapy improved significantly with the widespread availability of medications such as clopidogrel and statins. The use of these medications no doubt had an effect on patient outcomes.
      National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
      Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
      Finally, we note that women were under-represented in carotid revascularization trials.
      • Howard V.J.
      • Lutsep H.L.
      • Mackey A.
      • Demaerschalk B.M.
      • Sam 2nd, A.D.
      • Gonzales N.R.
      • et al.
      Influence of sex on outcomes of stenting versus endarterectomy: a subgroup analysis of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).
      It thus merits emphasis that women represented >40% of this study cohort, more than any of the published randomized controlled trials.
      Several limitations of this analysis need to be addressed. The inherent weaknesses in the use of a registry, such as the SVS-VR, have previously been addressed.
      • Jim J.
      • Rubin B.G.
      • Ricotta 2nd, J.J.
      • Kenwood C.T.
      • Siami F.S.
      • Sicard G.A.
      SVS Outcomes Committee. Society for Vascular Surgery (SVS) Vascular Registry evaluation of comparative effectiveness of carotid revascularization procedures stratified by Medicare age.
      These include the potential for treatment bias, absence of certain anatomic information (such as plaque morphology), and reporting bias. Perhaps the most important limitation in this study is the lack of a comparison group for patients treated with best medical therapy.
      The hesitation in recommending carotid revascularization to women is derived from two observations. This study addresses the first by focusing on the rates of perioperative complications with carotid revascularization. However, we were not able to determine if women had a lower event rate if treated solely with medical therapy. Further studies certainly are needed to determine the gender-based outcomes in medical management of carotid artery disease.
      Finally, our analysis was limited to 30-day outcomes. As such, potential differences between genders in the development of recurrent disease were not investigated. Despite these limitations, data from this study still provide valuable information about the effectiveness of carotid revascularization in women.

      Conclusions

      In this large, real-world analysis, women and men demonstrated similar rates of perioperative events after carotid revascularization that were true for both CEA and CAS and were independent of symptomatic status. These data suggest that, contrary to previous reports, women do not have a higher risk of adverse events than men after carotid revascularization.

      Author contributions

      Conception and design: JJ, FS, JR
      Analysis and interpretation: CK, FS
      Data collection: CK, FS
      Writing the article: JJ, ED, GU, NO, CK, FS, RW, JR
      Critical revision of the article: JJ, ED, GU, NO, CK, FS, RW, JR
      Final approval of the article: JJ, ED, GU, NO, CK, FS, RW, JR
      Statistical analysis: CK, FS
      Obtained funding: RW
      Overall responsibility: JJ

      Appendix

       Society for Vascular Surgery Outcomes Committee

      Rodney A. White, MD (Chair), Thomas E. Brothers, MD, Ellen D. Dillavou, MD, Patrick J. Geraghty, MD, David L. Gillespie, MD, Philip P. Goodney, MD, Jeffrey Jim, MD, Sarah Murphy, BS, Nicholas H. Osborne, MD, Joseph J. Ricotta, II, MD, Michael C. Stoner, MD, and Gilbert R. Upchurch, Jr, MD.

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