Outcomes after Arterial Endovascular Procedures Performed in Patients with an Elevated International Normalized Ratio Joshua A. Wilensky, Ahsan T. Ali, Mohammed M. Moursi, Guillermo A. Escobar, and Matthew R. Smeds, Little Rock, Arkansas
Background: Patients treated with anticoagulants frequently require urgent vascular procedures and elevated prothrombin time/international normalized ratio (INR) is traditionally thought to increase access site bleeding complications after sheath removal. We aimed to determine the safety of percutaneous arterial procedures on patients with a high INR in the era of modern ultrasound-guided access and closure device use. Methods: Patients undergoing arterial endovascular procedures at a single institution between October 2010 and November 2012 were reviewed (n ¼ 1,333). We retrospectively analyzed all patients with an INR > 1.5. Venous procedures, lysis checks, and cases with no documented INR within 24 hr were excluded. Sixty-five patients with 91 punctures were identified. A comparison group was then generated from the last 91 patients intervened on with INR < 1.6. Demographics, intraoperative data, and postoperative complications were compared. Results: The demographics were similar. More Coumadin use and higher INR were found in the study group (71/91 and 0/91, P ¼ 0.001; 2.3 and 1.1 sec, P ¼ 0.001, respectively), but there was more antiplatelet use in the control group (68/91 and 51/91, P ¼ 0.01). Intraoperatively, the sheath sizes, protamine use, closure device use, ultrasound guidance, brachial access, and procedure types were not statistically different. Sheath sizes ranged from 4 to 22F in the study group and 4 to 20F in the control group. Paradoxically, heparin was administered more frequently in the study group (64/91 and 50/91, P ¼ 0.046). Bleeding complications occurred more commonly in the study group (3/91 and 1/91, P ¼ 0.62), but this failed to reach significance and the overall complication rate in both groups was low. Conclusions: Endovascular procedures may be performed safely with a low risk of bleeding complications in patients with an elevated INR. Ultrasound guidance and closure device use may allow these cases to be performed safely, but a larger series may be needed to confirm this.
INTRODUCTION Performing endovascular interventions in anticoagulated patients can be a challenging balance between incurring the risks of increased bleeding Department of Vascular and Endovascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR. Correspondence to: Matthew R. Smeds, MD, Department of Vascular Surgery, University of Arkansas for Medical Sciences, 4301 West Markham Street #520-2, Little Rock, AR 72205, USA; E-mail: mrsmeds@ uams.edu Ann Vasc Surg 2015; 29: 22–27 http://dx.doi.org/10.1016/j.avsg.2014.05.019 Ó 2015 Elsevier Inc. All rights reserved. Manuscript received: February 12, 2014; manuscript accepted: May 18, 2014; published online: June 12, 2014.
22
and access site complications versus the risks related to stopping the anticoagulation, such as thromboembolism, or delaying the procedure to normalize the prothrombin time. The most common indications for warfarin therapy include atrial fibrillation, a mechanical heart valve, and venous thromboembolism.1,2 After warfarin cessation, it takes on average 4 days for the international normalized ratio (INR) to drop to 1.5 from a therapeutic level in most patients and the majority of surgeons believe that it is safe to perform an intervention at or below this value.3e8 After warfarin is restarted, it takes at least 3 days for the INR to reach therapeutic levels and often requires bridging therapy with intravenous or unfractionated
Vol. 29, No. 1, January 2015
subcutaneous heparin.9 Therefore, arranging procedures in patients on anticoagulation result in added costs not only from the bridging therapy and prolonged hospitalization, but also from case cancellation for patients with an unexpectedly high INR.10e13 In addition, anticoagulated patients who need a procedure performed in an urgent or emergent manner may have their cases delayed while waiting for normalization of their clotting parameters. The advent of arteriotomy closure devices and the increasing use of ultrasound-guided access for endovascular interventions have increased the safety of percutaneous vascular procedures.14e20 However, there have been few studies to date examining the efficacy of endovascular interventions in patients on anticoagulation. We performed a retrospective study to determine the safety of percutaneous procedures in patients with elevated INR.
METHODS A retrospective review of all patients undergoing percutaneous endovascular interventions from October 2010 to November 2012 was performed. We included for analysis all patients with INR > 1.5, and a size-matched comparison group, which was collected using the last 91 consecutive patients over the same time period with INR < 1.6. Venous procedures, lysis checks, and cases with no documented INR within 24 hr of the procedure were excluded. All procedures were performed at a single hospital by one of the 5 full-time academic surgeons and our study protocol was approved by the Institutional Review Board of the University of Arkansas for Medical Sciences. Patient charts and medical records were reviewed for demographic information, intraoperative data, vascular access site complications, 30-day postoperative adverse events, and clinical followup, as well as any secondary procedures performed after initial intervention. Vascular access site complications included pseudoaneurysm, retroperitoneal hemorrhage, arteriovenous fistula, or return to the operating room for any bleeding complication. Statistical Analysis Clinical features and outcomes were compared between the anticoagulated group and the control group. Categorical data were analyzed using a contingency table with Fisher’s exact test and twotailed P values. A paired t-test with two-tailed P values was used for analyzing continuous data.
Endovascular procedures with elevated INR 23
Table I. Baseline demographics
Male Age BMI Current smoker Current or ex-smoker Diabetes Hypertension CAD Antiplatelet use ASA Plavix Aggrenox ASA/plavix Coumadin use Perioperative INR
Elevated INR (n ¼ 91)
Control (n ¼ 91)
59 (65%) 60.1 26.1 32 (35%) 72 (79%) 27 (30%) 64 (70%) 32 (35%) 51 (56%) 42 (46%) 1 (1%) 0 (0%) 8 (9%) 71 (78%) 2.3
52 (57%) 62 26.2 48 (53%) 74 (81%) 36 (40%) 76 (84%) 29 (32%) 68 (75%) 30 (33%) 13 (14%) 1 (1%) 24 (26%) 0 (0%) 1.1
P value
0.36 0.33 0.88 0.02 0.85 0.21 0.05 0.75 0.01
0.001 0.001
ASA, American Society of Anesthesiologists; BMI, body mass index; CAD, coronary artery disease. Bold values represent P 1.5, resulting in 91 puncture sites. A control group was generated from the last 91 punctures (85 patients) intervened on with INR < 1.6. There were statistically more current smokers as well as more patients on antiplatelet therapy in the control group. As expected, there were more patients on Coumadin and a higher INR in the study group (71/91 vs. 0/91, P ¼ 0.001; 2.3 vs. 1.1, P ¼ 0.001, respectively). The remainder of the preoperative demographic variables was similar between the 2 groups (Table I). Within the study group, there were 44 (48%) punctures with an INR 1.6e2, 32 (35%) punctures with an INR 2.1e3, and 15 (17%) punctures with INR > 3. There was no difference between the groups in regards to whether the procedure was a diagnostic angiogram alone or a percutaneous intervention, with the majority (58/91 and 49/91, P ¼ 0.23) of both groups being interventions (Table II). However, there were statistically more lysis cases (9/91 vs. 1/91, P ¼ 0.02) as well as emergent cases (23/ 91 vs. 4/91, P ¼ 0.0001) performed in the study group as compared with the control group. There was a trend toward more endovascular aneurysm repair in the study group, but this did not reach statistical significance (17/91 and 8/91, P ¼ 0.08). Of note, brachial access was in 9 (10%) patients in the study group and 7 (8%) patients in the control group.
24 Wilensky et al.
Annals of Vascular Surgery
Table II. Procedure type
Diagnostic angiogram Intervention PTA or stent Lysis +/ EVAR/TEVAR Other Emergent procedure
Table IV. Sheath size
Elevated INR (n ¼ 91)
Control (n ¼ 91)
P value
33 58 29 9 17 3 23
42 49 36 1 8 4 4
0.23 0.23 0.35 0.02 0.08 1.0 0.0001
(36%) (64%) (32%) (10%) (19%) (3%) (25%)
(46%) (54%) (40%) (1%) (9%) (4%) (4%)
EVAR, endovascular aneurysm repair; PTA, percutaneous transluminal angioplasty; TEVAR, thoracic endovascular aneurysm repair. Bold values represent P 6 US guidance Heparin during case Protamine Closure device Angioseal Mynx Perclose Intervention Arm access
Control (n ¼ 91)
P value
43/91 (47%) 36/91 (40%) 12/91 (13%)
62/91 (68%) 23/91 (25%) 6/91 (7%)
0.007 0.06 0.24
Bold values represent P
Background: Patients treated with anticoagulants frequently require urgent vascular procedures and elevated prothrombin time/international normalized ratio (INR) is traditionally thought to increase access site bleeding complications after sheath removal. We aimed to determine the safety of percutaneous arterial procedures on patients with a high INR in the era of modern ultrasound-guided access and closure device use. Methods: Patients undergoing arterial endovascular procedures at a single institution between October 2010 and November 2012 were reviewed (n ¼ 1,333). We retrospectively analyzed all patients with an INR > 1.5. Venous procedures, lysis checks, and cases with no documented INR within 24 hr were excluded. Sixty-five patients with 91 punctures were identified. A comparison group was then generated from the last 91 patients intervened on with INR < 1.6. Demographics, intraoperative data, and postoperative complications were compared. Results: The demographics were similar. More Coumadin use and higher INR were found in the study group (71/91 and 0/91, P ¼ 0.001; 2.3 and 1.1 sec, P ¼ 0.001, respectively), but there was more antiplatelet use in the control group (68/91 and 51/91, P ¼ 0.01). Intraoperatively, the sheath sizes, protamine use, closure device use, ultrasound guidance, brachial access, and procedure types were not statistically different. Sheath sizes ranged from 4 to 22F in the study group and 4 to 20F in the control group. Paradoxically, heparin was administered more frequently in the study group (64/91 and 50/91, P ¼ 0.046). Bleeding complications occurred more commonly in the study group (3/91 and 1/91, P ¼ 0.62), but this failed to reach significance and the overall complication rate in both groups was low. Conclusions: Endovascular procedures may be performed safely with a low risk of bleeding complications in patients with an elevated INR. Ultrasound guidance and closure device use may allow these cases to be performed safely, but a larger series may be needed to confirm this.
INTRODUCTION Performing endovascular interventions in anticoagulated patients can be a challenging balance between incurring the risks of increased bleeding Department of Vascular and Endovascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR. Correspondence to: Matthew R. Smeds, MD, Department of Vascular Surgery, University of Arkansas for Medical Sciences, 4301 West Markham Street #520-2, Little Rock, AR 72205, USA; E-mail: mrsmeds@ uams.edu Ann Vasc Surg 2015; 29: 22–27 http://dx.doi.org/10.1016/j.avsg.2014.05.019 Ó 2015 Elsevier Inc. All rights reserved. Manuscript received: February 12, 2014; manuscript accepted: May 18, 2014; published online: June 12, 2014.
22
and access site complications versus the risks related to stopping the anticoagulation, such as thromboembolism, or delaying the procedure to normalize the prothrombin time. The most common indications for warfarin therapy include atrial fibrillation, a mechanical heart valve, and venous thromboembolism.1,2 After warfarin cessation, it takes on average 4 days for the international normalized ratio (INR) to drop to 1.5 from a therapeutic level in most patients and the majority of surgeons believe that it is safe to perform an intervention at or below this value.3e8 After warfarin is restarted, it takes at least 3 days for the INR to reach therapeutic levels and often requires bridging therapy with intravenous or unfractionated
Vol. 29, No. 1, January 2015
subcutaneous heparin.9 Therefore, arranging procedures in patients on anticoagulation result in added costs not only from the bridging therapy and prolonged hospitalization, but also from case cancellation for patients with an unexpectedly high INR.10e13 In addition, anticoagulated patients who need a procedure performed in an urgent or emergent manner may have their cases delayed while waiting for normalization of their clotting parameters. The advent of arteriotomy closure devices and the increasing use of ultrasound-guided access for endovascular interventions have increased the safety of percutaneous vascular procedures.14e20 However, there have been few studies to date examining the efficacy of endovascular interventions in patients on anticoagulation. We performed a retrospective study to determine the safety of percutaneous procedures in patients with elevated INR.
METHODS A retrospective review of all patients undergoing percutaneous endovascular interventions from October 2010 to November 2012 was performed. We included for analysis all patients with INR > 1.5, and a size-matched comparison group, which was collected using the last 91 consecutive patients over the same time period with INR < 1.6. Venous procedures, lysis checks, and cases with no documented INR within 24 hr of the procedure were excluded. All procedures were performed at a single hospital by one of the 5 full-time academic surgeons and our study protocol was approved by the Institutional Review Board of the University of Arkansas for Medical Sciences. Patient charts and medical records were reviewed for demographic information, intraoperative data, vascular access site complications, 30-day postoperative adverse events, and clinical followup, as well as any secondary procedures performed after initial intervention. Vascular access site complications included pseudoaneurysm, retroperitoneal hemorrhage, arteriovenous fistula, or return to the operating room for any bleeding complication. Statistical Analysis Clinical features and outcomes were compared between the anticoagulated group and the control group. Categorical data were analyzed using a contingency table with Fisher’s exact test and twotailed P values. A paired t-test with two-tailed P values was used for analyzing continuous data.
Endovascular procedures with elevated INR 23
Table I. Baseline demographics
Male Age BMI Current smoker Current or ex-smoker Diabetes Hypertension CAD Antiplatelet use ASA Plavix Aggrenox ASA/plavix Coumadin use Perioperative INR
Elevated INR (n ¼ 91)
Control (n ¼ 91)
59 (65%) 60.1 26.1 32 (35%) 72 (79%) 27 (30%) 64 (70%) 32 (35%) 51 (56%) 42 (46%) 1 (1%) 0 (0%) 8 (9%) 71 (78%) 2.3
52 (57%) 62 26.2 48 (53%) 74 (81%) 36 (40%) 76 (84%) 29 (32%) 68 (75%) 30 (33%) 13 (14%) 1 (1%) 24 (26%) 0 (0%) 1.1
P value
0.36 0.33 0.88 0.02 0.85 0.21 0.05 0.75 0.01
0.001 0.001
ASA, American Society of Anesthesiologists; BMI, body mass index; CAD, coronary artery disease. Bold values represent P 1.5, resulting in 91 puncture sites. A control group was generated from the last 91 punctures (85 patients) intervened on with INR < 1.6. There were statistically more current smokers as well as more patients on antiplatelet therapy in the control group. As expected, there were more patients on Coumadin and a higher INR in the study group (71/91 vs. 0/91, P ¼ 0.001; 2.3 vs. 1.1, P ¼ 0.001, respectively). The remainder of the preoperative demographic variables was similar between the 2 groups (Table I). Within the study group, there were 44 (48%) punctures with an INR 1.6e2, 32 (35%) punctures with an INR 2.1e3, and 15 (17%) punctures with INR > 3. There was no difference between the groups in regards to whether the procedure was a diagnostic angiogram alone or a percutaneous intervention, with the majority (58/91 and 49/91, P ¼ 0.23) of both groups being interventions (Table II). However, there were statistically more lysis cases (9/91 vs. 1/91, P ¼ 0.02) as well as emergent cases (23/ 91 vs. 4/91, P ¼ 0.0001) performed in the study group as compared with the control group. There was a trend toward more endovascular aneurysm repair in the study group, but this did not reach statistical significance (17/91 and 8/91, P ¼ 0.08). Of note, brachial access was in 9 (10%) patients in the study group and 7 (8%) patients in the control group.
24 Wilensky et al.
Annals of Vascular Surgery
Table II. Procedure type
Diagnostic angiogram Intervention PTA or stent Lysis +/ EVAR/TEVAR Other Emergent procedure
Table IV. Sheath size
Elevated INR (n ¼ 91)
Control (n ¼ 91)
P value
33 58 29 9 17 3 23
42 49 36 1 8 4 4
0.23 0.23 0.35 0.02 0.08 1.0 0.0001
(36%) (64%) (32%) (10%) (19%) (3%) (25%)
(46%) (54%) (40%) (1%) (9%) (4%) (4%)
EVAR, endovascular aneurysm repair; PTA, percutaneous transluminal angioplasty; TEVAR, thoracic endovascular aneurysm repair. Bold values represent P 6 US guidance Heparin during case Protamine Closure device Angioseal Mynx Perclose Intervention Arm access
Control (n ¼ 91)
P value
43/91 (47%) 36/91 (40%) 12/91 (13%)
62/91 (68%) 23/91 (25%) 6/91 (7%)
0.007 0.06 0.24
Bold values represent P
