Long-term Outcomes of Carotid Endarterectomy With Simultaneous Proximal Common Carotid Endovascular Intervention

Carotid bifurcation stenosis may coexist simultaneously with more proximal common carotid artery (CCA) atherosclerotic plaquing, primarily at the vessel origin in the aortic arch. Obtaining long-term outcomes data is vital to making any definitive conclusions on the efficacy of performing this dual treatment. Four cohorts were created for perioperative outcome analysis and Kaplan-Meier freedom from event analysis: carotid endarterectomy (CEA) in isolation for asymptomatic disease; CEA in isolation for symptomatic patients; CEA with proximal CCA endovascular intervention for asymptomatic stenosis; and CEA with proximal CCA intervention for symptomatic patients. Binary logistic multivariable regression was performed for a perioperative neurological event and 90-day mortality risk determination, and Cox multivariable regression analysis was performed for a long-term freedom from cumulative ischemic neurological event and long-term mortality analysis. Symptomatology and type of surgery (CEA with or without CCA intervention) were individual variables in the multivariable analysis. The neurological ischemic event in this study encompassed transient ischemic attack and stroke combined. We noted a statistically significant (P < .001) progressive escalation in rates (Fig 3) of perioperative neurological event, myocardial infarction, carotid re-exploration, 90-day mortality and combined neurological event, and 90-day mortality moving from (A) asymptomatic CEA in isolation to (B) symptomatic CEA in isolation to (C) asymptomatic CEA combined with proximal CCA intervention to (D) symptomatic CEA in combination with proximal CCA intervention. After surgery, freedom from cerebral ischemia and mortality for patients undergoing dual intervention is closely aligned with patients undergoing CEA in isolation (Figs 1 and 2), indicating quality protection from adverse events. Comparison of baseline characteristics is listed in Table I. Multivariable analysis for the outcomes of the perioperative neurological ischemic event (Table II), combined perioperative neuro event and 90-day mortality (Table III), long-term mortality (Table IV), and long-term neurological ischemic event (Table V) is presented. Despite high adverse perioperative event rates for the combined CEA and CCA treatment, there is likely a long-term stroke reduction and mortality benefit to this approach in symptomatic patients based on the strength of benefit in North American Symptomatic Carotid Endarterectomy Trial (NASCET) and event-free rates seen herein after initial hospital discharge. The benefit of treating asymptomatic dual ICA and CCA lesions remains vague as the lack of natural history data on asymptomatic dual lesions in combination with improved outcomes with medical therapy makes definitive conclusions challenging.Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table IComparison of baseline characteristics and perioperative variables across cohortsVariableAsymptomatic CEA in isolation (N = 109,511)Symptomatic CEA in isolation (N = 56,743)Asymptomatic CEA + proximal CCA Tx (N = 608)Symptomatic CEA + proximal CCA Tx (N = 339)P valueMean age, years70.6470.4669.4470.45<.001Male64.962.25244.8<.001Race<.001 Native American0.20.30.00.6 Asian1.01.00.80.3 Black4.15.63.12.7 Hawaiian and Pacific Islander0.10.10.00.0 White91.488.992.894.4 Unknown0.10.10.00.0 Multiracial3.14.03.32.1Hx of smoking75.472.188.386.7<.001Hypertension89.888.089.889.1<.001Diabetes mellitus36.435.329.330.7<.001CAD28.922.434.529.2<.001CHF11.310.514.515.6<.001COPD23.021.632.737.2<.001CRI19.816.417.815.0<.001Anemia (Hgb <10)91.293.090.889.1<.001No preoperative antiplatelet11.110.68.19.7.02No preoperative statin17.515.415.116.2<.001Symptomatic lesion within 6 months0.0100.00.0100.0N/ALocal/regional anesthesia8.56.44.13.8<.001Yes patch used88.886.293.384.4<.001Shunt used49.352.642.845.1<.001Protamine used70.072.174.878.5<.001Yes EEG used28.831.532.733.0<.001Stump pressure used11.210.011.911.5<.001CAD, Coronary artery disease; CCA, common carotid artery; CEA, carotid endarterectomy; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; EEG, electroencephalogram; Hgb, hemoglobin; Hx, history of; N/A, not applicable; Tx, treatment.Data are presented as % unless otherwise specified. Open table in a new tab Table IIRisks for a perioperative neurologic event—binary logistic regression using univariable risks for all patients included in the studyPerioperative neurologic event, % (n/N)Univariable P valueAdjusted odds ratio (95% CI)Multivariable P valueSimultaneous proximal CCA Tx Yes3.6 (34/947)<.0015.84 (4.80-7.11)<.001 No1.7 (2880/165,869)Age, years Yes neurologic event71.25<.011.007 (1.003-1.011).001 No neurologic event70.56Sex Male1.7 (566/41,391).597 Female1.8 (1164/65,904)Race Native American2.4 (10/419).570 Asian2.0 (34/1661).917 Black2.5 (191/7690).648 Hawaiian and Pacific Isles1.7 (2/118).267 White1.7 (2551/151,357).736 Unknown2.8 (6/217).672 Multiracial2.2 (124/5630).683History of smoking Active or former smoker1.7 (2122/124,317.042 Never smoker1.9 (796/42,884)History of HTN Yes1.8 (2692/149,162)<.0011.42 (1.23-1.63)<.001 No1.3 (226/18,039)Hx of DM Yes1.9 (1169/60,146)<.0011.15 (1.07-1.25)<.001 No1.6 (1749/107,055)Hx of CAD Yes1.8 (817/44,684).117 No1.7 (2101/122,517)CHF Yes1.9 (348/18,495).133 No1.7 (2570/148,706)Hx of COPD Yes1.7 (655/37,770).85 No1.7 (2263/129,431)Hx of CRI Yes1.8 (572/31,163).177 No1.7 (2346/136,038)Hx of anemia Yes1.7 (2666/153,510).374 No1.8 (252/13,691)Preoperative antiplatelet Yes1.7 (2520/148,970)<.0011.27 (1.14-1.42)<.001 Not2.2 (398/18,231)Preoperative statin Yes1.7 (2375/139,164).0071.14 (1.03-1.25).01 Not1.9 (543/28,037)Local anesthesia Yes1.8 (2710/154,283).217 Not1.6 (208/12,918)Patch Yes1.7 (2467/147,002)<.0011.38 (1.24-1.54)<.001 No2.2 (451/20,199)Shunt Yes1.5 (1276/83,006)<.0011.31 (1.21-1.41)<.001 No2.0 (1642/84,195)Protamine Yes1.7 (1978/118,044)<.0011.14 (1.5-1.23).002 No1.9 (934/48,802)EEG Yes1.7 (2025/117,128).442 No1.8 (884/49,583)Stump pressure used Yes1.8 (2641/148,666).0061.09 (0.96-1.24).184 No1.5 (269/18,004)Symptomatic lesion within 6 months Yes1.7 (1476/56,812)<.0011.98 (1.84-2.14)<.001 No1.3 (1442/0389)Postoperative MI Yes4 (117/1224)<.0015.84 (4.80-7.11)<.001 No1.7 (2801/165,977)CAD, Coronary artery disease; CCA, common carotid artery; CHF, congestive heart failure; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; DM, diabetes mellitus; EEG, electroencephalogram; HTN, hypertension; Hx, history of; MI, myocardial infarction; Tx, treatment. Open table in a new tab Table IIICombined perioperative neuro event and 90-day mortality—binary logistic regression analysis using univariable risks for eventVariableCombined event rate, % (n/N)Univariable P valueAdjusted odds ratio (95% CI)Multivariable P valueProximal CCA endovascular intervention Yes2.8 (4651/165,869)<.0012.13 (1.62-2.80)<.001 No2.8 (59/947)Age, years Yes neurologic event72.19<.0011.02 (1.01-1.02)<.001 No neurologic event70.53Sex Male2.8 (2831/101,295).415 Female2.9 (1887/65,904)Race Native American3.6 (15/419) Asian2.8 (47/1661) Black3.7 (288/7690).431 Hawaiian3.4 (4/118) White2.8 (4184/151,357) Multiracial3.7 (8/217) Other3.0 (171/5630History of smoking Active or former smoker2.9 (3544/124,317).23 Never smoker2.7 (1174/42,884)History of HTN Yes2.9 (4359/149,162)<.0011.31 (1.17-1.46)<.001 No2.0 (359/18,039)Hx of DM Yes3.3 (1984/60,146)<.0011.19 (1.19-1.26)<.001 No2.6 (2734/107,055)Hx of CAD Yes3.3 (1496/44,684)<.0011.14 (1.07-1.22)<.001 No2.6 (3222/122,517)Hx of COPD Yes3.5 (1314/37,770)<.0011.26 (1.18-1.35)<.001 No2.6 (3404/129,431)Hx of CRI Yes3.6 (1136/31,163)<.0011.18 (1.10-1.27)<.001 No2.6 (3582/136,038)Hx of anemia Yes4.4 (605/13,691)<.0011.53 (1.40-1.67)<.001 No2.7 (4113/153,510)Hx of CHF Yes4.5 (838/18,495)<.0011.41 (1.30-1.53)<.001 No2.6 (3880/148,706)Preoperative antiplatelet Yes3.6 (652/18,231)<.0011.29 (1.18-1.40)<.001 Not2.7 (4066/148,970)Preoperative statin Yes3.2 (887/28,037)<.0011.16 (1.07-1.25)<.001 Not2.8 (3831/139,164)Local regional anesthesia Yes2.6 (334/12,918) No2.8 (4384/154,283).098No patch Yes3.4 (690/20,199)<.0011.28 (1.17-1.40)<.001 No2.7 (4028/147,002)Shunt Yes3.2 (2662/84,195)<.0011.29 (1.21-1.37)<.001 No2.5 (2056/83,006)Protamine Yes2.7 (3213/118,044) No3.1 (1496/48,802)<.0011.13 (1.06-1.21)<.001EEG Yes2.8 (1383/49,583).615 No2.8 (3321/117,128)Stump pressure Yes2.9 (4273/148,666)<.0011.10 (0.99-1.22)<.001 No2.4 (432/18,004)Symptomatic lesion within 6 months Yes4.1 (2318/56,812)<.0011.96 (1.85-2.08)<.001 Not2.2 (2400/110,389)Postoperative MI Yes19.6 (240/1224)<.0017.58 (6.53-8.79)<.001 No2.7 (4478/165,977)CAD, Coronary artery disease; CCA, common carotid artery; CHF, congestive heart failure; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; DM, diabetes mellitus; EEG, electroencephalogram; HTN, hypertension; Hx, history of; MI, myocardial infarction. Open table in a new tab Table IVRisks for mortality in long-term follow-up—Cox regression using univariable risksVariableMortality in LTFU, % (n/N)Univariable P valueHazard ratio (95% CI)Multivariable P valueProximal CCA endovascular intervention Yes11.8 (112/947).0091.40 (1.16-1.69)<.001 No9.3 (15,461/165,866)Age, years Yes mortality in LTF73.3<.0011.04 (1.04-1.04)<.001 No mortality in LTF70.3Sex Male9.5 (9671/101,292)<.0011.07 (1.03-1.12)<.001 Female9.0 (5959/65,901)Race Native American7.6 (32/419) Asian5.5 (91/1661) Black9.9 (759/7690) Hawaiian9.3 (11/118) White9.5 (14,398/151,351)1.07 (1.03-1.10)<.001 Multiracial5.1 (11/217) Other5.7 (321/5630)History of smoking Active or former smoker10.0 (12,438/124,315)<.0011.33 (1.27-1.40)<.001 Never smoker7.4 (3192/42,880)History of HTN Yes9.6 (14,340/149,159)<.0011.08 (1.01-1.16).027 No7.2 (1290/18,036)History of DM Yes11.1 (6652/60,145)<.0011.30 (1.25-1.35)<.001 No8.4 (8978/107,050)History of CAD Yes12.5 (5603/44,684)<.0011.20 (1.15-1.25)<.001 No8.2 (10,027/122,511)History of COPD Yes13.4 (5045/37,770)<.0011.60 (1.53-1.67)<.001 No8.2 (10,585/129,425)History of CRI Yes14.7 (4577/31,160)<.0011.33 (1.27-1.39)<.001 No8.1 (11,053/136,035)History of anemia Yes23.6 (3228/13,688)<.0011.97 (1.86-2.09)<.001 No8.1 (12,402/153,507)History of CHF Yes17.0 (3145/18,495)<.0011.76 (1.68-1.85)<.001 No8.4 (12,485/148,700)Preoperative antiplatelet Yes9.1 (13,603/1,148,967) Not11.1 (2027/18,228)<.0011.11 (1.05-1.18)<.001Preoperative statin Yes8.9 (12,397/139,161) Not11.5 (3233/28,034)<.0011.20 (1.12-1.29)<.001Local regional anesthesia Yes10.4 (1349/12,915)<.0011.00 (0.93-1.08).968 No9.3 (14,281/154,280)Patch Yes9.2 (13,466/146,999) No10.7 (2164/20,196)<.0011.11 (1.04-1.18)<.001Shunt Yes9.6 (8107/84,194)<.0011.07 (1.02-1.12).004 No9.1 (7523/83,001)Protamine use Yes8.9 (10,452/118,042) No10.5 (5126/48,801)<.0011.01 (0.97-1.05).639EEG use Yes10.1 (5000/49,580)<.0011.00 (0.95-1.05).986 No9.0 (10,563/117,128)Stump pressure use Yes6.8 (1227/18,004) No9.6 (14,332/148,663)<.0011.13 (1.06-1.21)<.001Symptomatic lesion within 6 months Yes8.4 (4797/56,810) No9.8 (10,833/110,385)<.0011.38 (1.32-1.46)<.001Postoperative MI Yes26.2 (321/1224)<.0012.20 (1.91-2.52)<.001 No9.2 (15,309/165,971)Antiplatelet on discharge Yes9.6 (7092/73,726)<.0011.15 (1.10-1.19)<.001 No9.1 (8538.93,469)Statin on discharge Yes8.3 (12,151/146,227) No16.6 (3479/20,968)<.0011.71 (1.59-1.84)<.001Smoking at LTF Yes9.1 (1640/18,010)<.0011.00 (0.95-1.06).929 No8.3 (9119/110,242)Antiplatelet at LTF Yes9.1 (11,765/128,825) No10.1 (3865/38,361)<.0011.15 (1.09-1.21)<.001Anticoagulation at LTF Yes8.4 (10,209/121,933) No12.0 (5421/45,253)<.0011.07 (0.98-1.17).114Statin at LTF Yes9.2 (7810/84,458) No9.5 (7820/82,728).1511.01 (0.96-1.06).688Ipsilateral recurrent stenosis >70% at LTF Yes8.4 (257/3059).9771.10 (0.97-1.25).128 No8.4 (10,502/125,193)Postoperative neuro event Yes21.5 (627/2918)<.0012.44 (2.22-2.69)<.001 No9.1 (15,003/164,277)CAD, Coronary artery disease; CCA, common carotid artery; CHF, congestive heart failure; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; DM, diabetes mellitus; EEG, electroencephalogram; HTN, hypertension; LTF, long-term follow-up; MI, myocardial infarction. Open table in a new tab Table VRisks for a neurologic ischemic event at long-term follow-up—Cox regression using univariable risksVariableNeurologic event in LTFU, % (n/N)Univariable P valueHazard ratio (95% CI)Multivariable P valueProximal CCA endovascular intervention Yes3.6 (34/947).0621.62 (1.14-2.29).007 No2.5 (4357/165,869)Age, years Yes neurologic event71.2<.0011.006 (1.00-1.01)<.001 No neurologic event70.6Sex Male2.6 (2645/101,294) Female2.7 (1750/65,904).584Race Native American2.9 (12/419) Asian2.6 (43/1661) Black3.5 (268/7690) Hawaiian3.4 (4/118) White2.6 (3868/151,356) Multiracial4.1 (9/217)<.0011.67 (0.62-2.21).647 Other3.4 (191/5630)History of smoking Active or former smoker2.6 (3197/124,317).0131.01 (0.94-1.08).826 Never smoker2.6 (1198/42,883)History of HTN Yes2.7 (3994/149,162)<.0011.13 (1.01-1.26).03 No2.2 (401/18,038)History of DM Yes2.8 (1694/60,146)<.0011.08 (1.01-1.15).028 No2.5 (2701/107,054)History of CAD Yes2.6 (1180/44,684).85 No2.6 (3215/122,516)History of COPD Yes2.6 (977/37,770) No2.6 (3418/129,430).57History of CRI Yes2.6 (805/31,163).595 No2.6 (3590/136,037)History of anemia Yes2.6 (351/13,690).653 No2.6 (4044/153,510)History of CHF Yes2.8 (514/18,495).179 No2.6 (3881/148,705)Preoperative antiplatelet Yes2.6 (3836/148,970) No3.1 (559/18,230)<.0011.13 (1.02-1.25).016Preoperative statin Yes2.6 (3649/139,164) No2.7 (746/28,036).714Local regional anesthesia Yes2.4 (308/12,917) No2.6 (4087/154,283).073Patch Yes2.5 (3739/147,002) No3.2 (6565/20,198)<.0011.27 (1.16-1.40)<.001Shunt Yes2.9 (2402/84,195)<.0011.16 (1.09-1.24)<.001 No2.4 (1993/83,005)Protamine use Yes2.6 (3019/118,044) No2.8 (1368/48,802).0051.11 (1.04-1.19).003EEG use Yes2.7 (1351.49,583).119 No2.6 (3035/117,128)Stump pressure use Yes2.3 (406/18,004) No2.7 (3981/148,666)<.0011.10 (0.98-1.23).093Symptomatic lesion within 6 months Yes4.5 (2584/56,812)<.0013.07 (2.83-3.34)<.001 No1.6 (1811/110,388)Postoperative MI Yes10.3 (126/1224)<.0013.17 (2.58-3.89)<.001 No2.6 (4269/165,976)Antiplatelet on discharge Yes3.2 (2352/73,730)<.0011.27 (1.19-1.35)<.001 No2.2 (2043/93,470)Statin on discharge Yes2.6 (3756.146,231) No3.0 (639/20,969)<.0011.24 (1.13-1.37)<.001Smoking at LTF Yes2.6 (3756/146,231)<.0011.08 (0.99-1.17).102 No2.9 (3169/110,243)Antiplatelet at LTF Yes2.4 (3102/128,831) No3.4 (1293/38,361)<.0011.34 (1.24-1.44)<.001Anticoagulation at LTF Yes2.8 (3471/121,935)<.0011.75 (1.56-1.96)<.001 No2.0 (924/45,257)Statin at LTF Yes3.4 (2888/84,460)<.0011.08 (0.99-1.18).087 No1.8 (1507/82,732)Ipsilateral recurrent stenosis >70% at LTF Yes5.2 (159/3059)<.0011.60 (1.36-1.87)<.001 No2.9 (3639/125,195)CAD, Coronary artery disease; CCA, common carotid artery; CHF, congestive heart failure; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; DM, diabetes mellitus; EEG, electroencephalogram; HTN, hypertension; LTF, long-term follow-up; MI, myocardial infarction. 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