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J ENDOVASC THER 2014;21:822–828
^ CLINICAL
INVESTIGATION ——————————————————————————
^
Safety and Effectiveness of a Novel Vascular Closure Device: A Prospective Study of the ExoSeal Compared to the Angio-Seal and ProGlide Kaffer Kara, MD1; Amir A. Mahabadi, MD2; Hanna Rothe2; Patrick Muller, MD1; Jan Kruger, MD1; ¨ ¨ 1 3 1 Horst Neubauer, MD ; Oliver Klein-Wiele, MD ; Andreas Mugge, MD ; Philipp Kahlert, MD2; ¨ 2 and Raimund Erbel, MD 1
Cardiovascular Center, St. Josef Hospital, Ruhr-University Bochum, Germany. 2Department of Cardiology, West-German Heart Center Essen, University of Duisburg- Essen, Germany. 3 Department of Cardiology, University of Witten-Herdecke, Germany. ^
^
Purpose: To prospectively assess the safety and efficacy of a novel absorbable vascular closure device (ExoSeal) in patients undergoing cardiac catheterization with femoral access compared to the established collagen-based (Angio-Seal) and suture-mediated (ProGlide) closure devices. Methods: This prospective, observational, dual-center, non-randomized, non-blinded study enrolled 1013 patients (65.1611.8 years) undergoing cardiac catheterization via a common femoral artery access in which hemostasis was achieved using a vascular closure device (255 Angio-Seal, 258 ProGlide, and 500 ExoSeal). In hospital complications (bleeding, hematoma, pseudoaneurysm, vessel occlusion, dissection, and arteriovenous fistula) of the puncture site and device failures (persistent bleeding) were recorded and compared for ExoSeal vs. the established devices (Angio-Seal þ ProGlide). Results: There were more complications after utilization of ExoSeal compared to established devices (3.6% vs. 1.2%, p¼0.012). No significant difference was observed in the device success rate between the established vascular closure devices (96.3%) and the novel device (94.8%, p¼0.28). Considering each closure system, Angio-Seal had the lowest complication rate (0.4%) and the highest efficacy (99.2%); the latter differed significantly from ExoSeal (94.8%, p¼0.001). Logistic regression analysis revealed a .3-fold odds of complications when using ExoSeal, which remained unchanged in multivariate analysis. Conclusion: Utilization of the novel vascular closure device is associated with a higher complication rate and a similar device failure rate compared to collagen-based and suturemediated devices, with Angio-Seal having the lowest complication and device failure rates. J Endovasc Ther. 2014;21:822–828 Key words: vascular closure devices, femoral artery access, vascular access, hemostasis, complications, collagen-based closure device, suture-mediated closure device, absorbable plug ^ ^
Vascular complications at the puncture site are still the most frequent complications in interventional cardiology and are associated with increased morbidity and mortality.1–3
The 1-year mortality in patients with vascular complications at the puncture site is 7.5% compared to 1.1% for those without complications.4 Moreover, most of the complications
The authors declare no association with any individual, company, or organization having a vested interest in the subject matter/products mentioned in this article. Corresponding author: Kaffer Kara, MD, Cardiovascular Center, St. Josef Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany. E-mail: [email protected] Q 2014 INTERNATIONAL SOCIETY
OF
ENDOVASCULAR SPECIALISTS
doi:10.1583/14-4744MR.1
Available at www.jevt.org
J ENDOVASC THER 2014;21:822–828
COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
at the puncture site require additional treatment, such as manual compression, transfusion, and transcatheter or surgical therapy. These are associated with further patient discomfort and extended hospital stay. Vascular closure devices (VCD) are well established in percutaneous diagnostic and therapeutic procedures. Over more than 20 years of experience, many studies and metaanalyses have documented the safety and effectiveness of VCDs in patients undergoing transfemoral catheterization.5–9 The risk of complications is not increased compared to manual compression, which is still the gold standard to achieve hemostasis at the puncture site. The most common types of VCD are collagen-based followed by suture-mediated.10 Recently, a novel vascular closure device with an absorbable plug has been developed. The synthetic polyglycolic acid plug is placed extravascularly without impeding the arterial blood flow; it is completely absorbed within 60 to 90 days. Major benefits of this new absorbable advice are its deployment through the existing procedure sheath without the need for sheath exchange and the avoidance of material in the vessel lumen. There is a lack of large prospective studies investigating the safety profile of this new absorbable VCD compared to the established VCDs. Therefore, the aim of this prospective observational study was to assess the efficacy and safety of a new absorbable VCD compared to individual collagen-based and suture-mediated VCDs in patients undergoing transfemoral cardiac catheterization.
METHODS Study Design This study was a prospective, observational, dual center, non-randomized analysis of consecutive patients undergoing coronary catheterization for diagnostic or therapeutic procedures via a 6-F transfemoral sheath. Indications for coronary angiography included acute coronary syndrome, known stenosis of one coronary artery, positive stress-testing, typical angina combined with extended risk factor profile, or other indication including
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patients staged for kidney or liver transplantation. According to the study protocol, the participating physician was to use any of the 3 study VCDs (6-F only) at his/her discretion to close the femoral artery puncture without giving preference to any VCD in special situations. A VCD was not used if the puncture was through the posterior wall, if there were multiple punctures, or if a VCD at the puncture site had been used within the last 90 days. Patients did not receive a VCD if fibrinolytic drugs were given. Only experienced personnel performed the femoral artery puncture and closure device deployment. Participating physicians had experience of at least 500 transfemoral catheterizations and at least 50 cases with each VCD. Moreover, physicians using the novel VCD had been previously certified by the manufacturer. The examiners periodically reviewed the number of each utilized VCD to achieve a homogeneous application of the devices. After deployment of the VCD, the physician filled out a data entry form indicating the device type and size, duration of the deployment procedure, deployment success or failure (and cause), and any patient discomfort. Within 6 hours and before discharge, a physician examined the puncture site and completed another data entry form regarding the examination. If there was any complication, dedicated study personnel were called to record the event and monitor any necessary procedure or treatment (e.g., pictures were taken of any hematoma).
Study Devices The ExoSeal VCD (Cordis Corporation, Bridgewater, NJ, USA) is a novel device that seals the puncture with a plug applied on the outside of the vessel wall, without impeding blood flow because no material remains inside the artery. The plug consists of synthetic polyglycolic acid that is fully reabsorbed within 60 to 90 days. The VCD is placed though the existing procedure sheath over a nitinol indicator wire with a visual display on the handle; a pulsatile bleed-back indicator shows the correct position of the plug when it
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COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
leaves the artery and is placed on the extravascular surface of the femoral artery access site in the puncture channel. Hemostasis is achieved after 2 minutes of manual compression. More details on device deployment can be found elsewhere.11,12 The Angio-Seal device (St. Jude Medical, St. Paul, MN, USA) consists of an absorbable intraluminal component (‘‘anchor’’) and a small collagen plug.13–17 After sheath exchange, the anchor is deployed intraluminally such that the arterial wall and the arteriotomy site are ‘‘sandwiched’’ between the anchor and the collagen plug, inducing hemostasis. The ProGlide VCD (Abbott Vascular, Abbott Park, IL, USA) is a suture-mediated closure system utilizing a single monofilament polypropylene suture. This device is composed of a plunger, handle, guide, and a sheath. After sheath exchange, the needles are placed around the puncture site and a suture loop is formatted by depressing a plunger on the device. The device is then removed, leaving behind the suture tails. A knot is tied and pushed toward the arteriotomy to achieve hemostasis.17–19
VCD Technique After administration of local anesthetic using a 23-G Terumo spinal needle, the femoral artery (usually the right) was palpated using the bony landmarks of the iliac crest and the symphysis. If the anatomy was uncertain (e.g., in obese patients), fluoroscopy was performed to locate the femoral head. The 18-G needle was advanced toward the artery until the spurt of pulsatile blood was seen (no ultrasound guidance is used in our clinical practice). This was followed by the introduction of a guidewire, which is advanced gently into the artery (modified Seldinger technique). After removal of the puncture needle, a 6-F sheath was inserted. For diagnostic procedures, patients received 2500 units of unfractionated heparin; in therapeutic procedures, 7500 to 10,000 (weightadjusted) units of unfractionated heparin were administered during the intervention. After the procedure, the VCD was applied according the instructors for use of each device. No
J ENDOVASC THER 2014;21:822–828
additional compression bandages were used in any case. Following the intervention, patients were supine for 6 hours. They were examined for access site complications with inspection of the puncture within 6 hours and before discharge. If any complication occurred, the subsequent procedures were recorded in detail. When no complications were noted, patients were discharged home with instructions to report immediately any swelling, hematoma, or pain.
Definitions and Data Capture Device failure after utilization of the VCD was defined as persistent bleeding requiring subsequent manual compression until hemostasis was achieved and the use of a compression bandage for 24 hours. In-hospital complications included bleeding, hematoma, pseudoaneurysm, vessel occlusion, dissection, and arteriovenous fistula. Complications were divided into major and minor as defined in previously published studies.19 Major complications were those requiring any endovascular or surgical intervention. Bleeding requiring transfusion or decreasing hemoglobin .2 g/dL was also considered a major complication. Moreover, hospitalization extended because of any puncture site complication was also recorded as a major complication. Minor complications included any observed events not requiring an intervention or increasing the hospital length of stay. Hematomas .3 cm in diameter were considered minor complications when no intervention was necessary. Patient age, sex, and traditional risk factors (diabetes, hypertension, hyperlipidemia, obesity, and history of smoking) were systematically recorded. Diabetes and hyperlipidemia were defined by a history of or being on medical treatment for the disease or first diagnosis during the hospital stay. Hypertension was defined as systolic blood pressure .140 mmHg or diastolic blood pressure .90 mmHg measured several times or intake of antihypertensive medication. Smoking was classified as current, former, or no history of smoking. Moreover, the antiplatelet or anticoagulation regimen was documented.
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COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
825
^
^ TABLE 1 Patient Characteristics Overall (n¼1013)
Angio-Seal þ ProGlide (n¼513)
ExoSeal (n¼500)
p
65.1611.8 704 (69.5%) 285 (28.1%) 924 (91.2%) 264 (26.1%) 760 (75.0%) 148 (14.6%) 170 (16.8%)
65.4611.7 376 (73.3%) 167 (32.6%) 484 (94.3%) 144 (28.1%) 398 (77.6%) 76 (14.8%) 89 (17.3%)
65.0611.9 328 (65.6%) 118 (23.6%) 440 (88.0%) 120 (24.0%) 362 (72.4%) 72 (14.4%) 81 (16.2%)
0.81 0.008 0.002 ,0.0001 0.145 0.057 0.87
430 446 137 450
212 249 52 270
218 197 85 180
Age, y Men Obesity Hypertension Diabetes Hyperlipidemia Smoking Former Antiplatelet therapy Single Dual None Therapeutic procedure
(42.4%) (44.0%) (13.5%) (44.4%)
(41.3%) (48.5%) (10.1%) (52.6%)
(43.6%) (39.4%) (17.0%) (35.9%)
0.009
,0.0001
^
^ Continuous data are presented as the means 6 standard deviation; categorical data are given as the counts/sample (percentage).
RESULTS
Statistical Analysis Patient characteristics are presented as mean 6 standard deviation for continuous variables and as count (percentage) for dichotomous traits. Data were analyzed for ExoSeal vs. the established VCDs (AngioSeal þ ProGlide). Differences in complication rates between these groups were explored using the Fisher exact test. Logistic regression analysis was used to determine an association between ExoSeal and complications. Multivariable analysis included the following variables: age, gender, obesity, hypertension, smoking, hyperlipidemia, diabetes, and therapeutic procedure. P,0.05 indicated statistical significance. All computations were performed using SPSS software (version 20.0; IBM Corporation, Somers, NY, USA).
From 2012 to 2013, 1013 patients (704 men; mean age 65.1611.8 years) were enrolled in this study. Of the performed procedures (255 Angio-Seal, 258 ProGlide, 500 ExoSeal), 563 were diagnostic and 450 were therapeutic. Patient details are shown in Table 1. In the total cohort, 24 (2.4%) complications were observed (Table 2): 18 (1.8%) minor and 6 (0.6%) major. In all, 18 hematomas (13 ExoSeal, 4 ProGlide, and 1 Angio-Seal) were classified as minor complications. One ExoSeal patient had a hematoma with a decrease in hemoglobin .2 g/dL. In 3 patients with increasing hematoma, manual compression and compression bandage were necessary, delaying hospital discharge (2 ExoSeal and 1 ProGlide). A pseudoaneurysm was observed in 1 ExoSeal patient and an arteriovenous fistula in another.
^
^ TABLE 2 Complication and Device Failure Rates for Each Vascular Closure Device Angio-Seal (n¼255) Complications Major Minor Device failure
^
1 0 1 2
(0.4%) (0%) (0.4%) (0.8%)
ProGlide (n¼258) 5 1 4 17
(1.9%) (0.4%) (1.6%) (6.6%)
ExoSeal (n¼500) 18 5 13 26
(3.6%) (1.0%) (2.6%) (5.2%)
Total (n¼1013) 24 6 18 45
(2.4%) (0.6%) (1.8%) (4.4%)
^
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COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
J ENDOVASC THER 2014;21:822–828
^
^ TABLE 3 Complication Rate of Each Vascular Closure Device Stratified by Procedure Type
Diagnostic procedures Therapeutic procedures
Angio-Seal
ProGlide
ExoSeal
1/150 (0.7%) 0/105 (0%)
1/93 (1.1%) 4/165 (2.4%)
6/320 (1.9%) 12/180 (6.7%)
^
^
There was a significantly higher complication rate after utilizing the ExoSeal compared to the established VCDs (3.6% vs. 1.2%, p¼0.012). Considering each VCD separately, there were higher complication rates with the ExoSeal compared to the Angio-Seal (3.6% vs. 0.4%, p¼0.004) and the ProGlide (3.6% vs. 1.6%, p¼0.148), though the latter was not statistically significant. This trend was also seen for minor and major complications, again not reaching statistical significance due to the small numbers of complications in each group. Table 3 shows the complication rate of each VCD stratified for diagnostic and therapeutic procedures. In logistic regression, the application of the ExoSeal was associated with a .3-fold increased risk of complications (Table 4). The incidence of complications did not decline with growing ExoSeal experience (3 in January-June 2012, 2 in July-December 2012, 9 in January-June 2013, and 4 in July-December 2013). Overall device failure occurred in 45 (4.4%) patients, and hemostasis was achieved by manual compression and compression bandage (Table 2). Therefore, overall device success was 95.6%. There was no significant difference in success rates between the established VCDs (96.3%) and the novel VCD (94.8%, p¼0.28). Considering each VCD, Angio-Seal (0.8%) had lowest device failure
followed by ExoSeal (5.2%) and ProGlide (6.6%), with significant differences for AngioSeal vs. ProGlide (p,0.001) and Angio-Seal vs. ExoSeal (p,0.0001). In logistic regression analysis, the use of ExoSeal was not associated with greater device failure (Table 4).
DISCUSSION This prospective study compared the safety and effectiveness of established VCDs (AngioSeal and ProGlide) with a novel VCD (ExoSeal) after diagnostic and therapeutic cardiac catheterization using a 6-F sheath. There were 3 times as many complications after ExoSeal than the established VCDs. Device failure rates were not significantly different between the groups. Considering each VCD, AngioSeal had the fewest complications and the highest efficacy rate. A notable strength of our study was the excellent experience of the operators with VCDs and the high number of patients enrolled. Most recently executed studies and registries found improving safety profiles for VCDs compared to manual compression2,20 after transfemoral cardiac catheterization. The largest published registry to date, which included 1,861,566 patients, demonstrated good performance of VCDs compared to manual compression in patients undergoing percuta-
^
^ TABLE 4 Logistic Regression Analyses of Complications and Device Failure for the ExoSeal Compared to the Established Vascular Closure Devices Complications
Device Failure
Model
Odds Ratio (95% CI)
p
Odds Ratio (95% CI)
p
Unadjusted Multivariate*
3.16 (1.25 to 8.03) 3.21 (1.20 to 8.37)
0.016 0.017
1.43 (0.78 to 2.62) 1.42 (0.75 to 2.67)
0.25 0.28
^
^ * Adjusted for age, gender, obesity, hypertension, smoking, hyperlipidemia, diabetes, and therapeutic procedure. CI: confidence interval.
J ENDOVASC THER 2014;21:822–828
neous coronary interventions.18 The utilization of Angio-Seal or ProGlide reduced the vascular complication rate by .30%.20 This escalating performance profile for VCDs may be explained partly by the increasing technical development of the devices (less cumbersome) and the growing experience in handling them. Both the collagen-based and the suturemediated VCDs affect the lumen of the vessel, which may be a source of complications (e.g., vessel occlusion).13 Therefore, a VCD such as ExoSeal, which does not remain in the vessel lumen, could further reduce complications. Moreover, frequent sheath exchanges, which are necessary with the established VCDs but not with the ExoSeal, may be a source of complications.21 These positive features of ExoSeal could be major benefits of this new absorbable device. The first randomized trial (ECLIPSE: Ensure’s Vascular Closure Device Speeds Hemostasis) compared the performance of ExoSeal to manual compression in patients undergoing coronary or peripheral procedures.12 This study showed more vascular complications at the puncture site in the ExoSeal group (8.5% vs. 4.0%) for the secondary safety composite endpoint, but the difference was not statistically significant (p¼0.14). Another retrospective single-center analysis reported low complication rates (1.2%) for the use of the novel VCD in diagnostic and interventional procedures.11 To the best of our knowledge, no other prospective study has compared the safety and efficacy of this novel VCD against established closure systems. However, despite the previously described features suggesting improved safety profiles with the ExoSeal, we saw significantly higher complication rates with the novel VCD compared to the established devices. It has to be acknowledged that the complication rate of ExoSeal, though higher than the comparator group in our cohort, was still moderate. The low complication rate of Angio-Seal þ ProGlide as described in our study is comparable to previously published data.6,7,17,20 There was no significant difference in device failure for ExoSeal compared to the established VCDs. The observed low device
COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
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failure rate for Angio-Seal and higher rate for ProGlide are known from previously published data.20
Limitations A major limitation of this study was the lack of randomization. Hence, the groups were not well matched in all aspects. In the Angio-Seal þ ProGlide group, hypertension, obesity, therapeutic procedures, and male patients were more frequent; moreover, more patients received dual antiplatelet therapy. Although therapeutic procedures and more intensive antiplatelet therapy are known risk factors for complications, the complication rate was higher for the ExoSeal group despite the group’s lower frequency of interventions.22 Another limitation of this study is that Angio-Seal was introduced .20 years ago and there is a lot of experience with this device. It might be possible that with increasing technical development of the ExoSeal and the growing experience in handling the new device, the complication rates will be reduced in future.
Conclusion Utilization of the ExoSeal is associated with higher complication rates compared to collagen-based (Angio-Seal) and suture-mediated (ProGlide) VCDs, with the Angio-Seal having the lowest complication and device failure rates.
REFERENCES 1. Manoukian SV, Feit F, Mehran R, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY Trial. J Am Coll Cardiol. 2007;49: 1362–1368. 2. Marso SP, Amin AP, House JA, et al. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA. 2010;303:2156– 2164. 3. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart Disease and Stroke Statistics — 2011 Update. A report from the American Heart Association 2011. Circulation. 2011;123:e18–e209.
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4. Omoigui NA, Califf RM, Pieper K, et al. Peripheral vascular complications in the coronary angioplasty versus excisional atherectomy trial (CAVEAT-I). J Am Coll Cardiol. 1995;26: 922–930. 5. Madigan JB, Ratnam LA, Belli AM. Arterial closure devices. A review. J Cardiovasc Surg. 2007;48:607–624. ¨ 6. Koreny M, Riedmuller E, Nikfardjam M, et al. Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and metaanalysis. JAMA 2004;291:350–357. 7. Nikolsky E, Mehran R, Halkin A, et al. Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: a meta-analysis. J Am Coll Cardiol. 2004;44:1200–1209. 8. Vaitkus PT. A meta-analysis of percutaneous vascular closure devices after diagnostic catheterization and percutaneous coronary intervention. J Invasive Cardiol. 2004;16:243–246. 9. Behan MW, Large JK, Patel NR, et al. A randomised controlled trial comparing the routine use of an Angio-Seal STS device strategy with conventional femoral haemostasis methods in a district general hospital. Int J Clin Pract. 2007;61:367–372. 10. Weinstein M. Vascular Closure. In: Cardiovascular Device Handbook 2003. New York: J.P. Morgan Securities Inc.; 2003:91–95. 11. Boschewitz JM, Andersson M, Naehle CP, et al. Retrospective evaluation of safety and effectiveness of the EXOSEAL vascular closure device for single vascular closure and closure after repeat puncture in diagnostic and interventional radiology: single-center experience. J Vasc Interv Radiol. 2013;24:698–702. 12. Wong SC, Bachinsky W, Cambier P, et al. A randomized comparison of a novel bioabsorbable vascular closure device versus manual compression in the achievement of hemostasis after percutaneous femoral procedures: the ECLIPSE (Ensure’s Vascular Closure Device Speeds Hemostasis Trial). JACC Cardiovasc Interv. 2009;2:785–793.
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13. Kara K, Mahabadi AA, Berg MH, et al. Utilization of collagen-based vascular closure devices in patients with severe peripheral artery disease. J Invasive Cardiol. 2013;25:19–22. 14. Kara K, Kahlert P, Mahabadi AA, et al. Comparison of collagen-based vascular closure devices in patients with vs. without severe peripheral artery disease. J Endovasc Ther. 2014;21:79–84. 15. Henry M, Amor M, Allaoui M, et al. A new access site management tool: the Angio-Seal hemostatic puncture closure device. J Endovasc Surg. 1995;2:289–296. ¨ 16. Beyer-Enke SA, Soldner J, Zeitler E. Immediate sealing of arterial puncture site following femoropopliteal angioplasty: a prospective randomized trial. Cardiovasc Intervent Radiol. 1996;19:406–410. 17. Schwartz BG, Burstein S, Economides C, et al. Review of vascular closure devices. J Invasive Cardiol. 2010;22:599–607. 18. Tavris DR, Wang Y, Jacobs S, et al. Bleeding and vascular complications at the femoral access site following percutaneous coronary intervention (PCI): an evaluation of hemostasis strategies. J Invasive Cardiol. 2012;24:328–334. 19. Ansel G, Yakubov S, Neilsen C, et al. Safety and efficacy of staple-mediated femoral arteriotomy closure: results from a randomized multicenter study. Catheter Cardiovasc Interv. 2006; 67:546–553. 20. Martin JL, Pratsos A, Magargee E, et al. A randomized trial comparing compression, Perclose Proglide and Angio-Seal VIP for arterial closure following percutaneous coronary intervention: the CAP trial. Catheter Cardiovasc Interv. 2008;71:1–5. 21. Shammas NW, Allie D, Hall P, et al. Predictors of in-hospital and 30-day complications of peripheral vascular interventions using bivalirudin as the primary anticoagulant: results from the APPROVE Registry. J Invasive Cardiol. 2005;17:356–359. 22. Ricci MA, Trevisani GT, Pilcher DB. Vascular complications of cardiac catheterization. Am J Surg. 1994;167:375–378.
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^ CLINICAL
INVESTIGATION ——————————————————————————
^
Safety and Effectiveness of a Novel Vascular Closure Device: A Prospective Study of the ExoSeal Compared to the Angio-Seal and ProGlide Kaffer Kara, MD1; Amir A. Mahabadi, MD2; Hanna Rothe2; Patrick Muller, MD1; Jan Kruger, MD1; ¨ ¨ 1 3 1 Horst Neubauer, MD ; Oliver Klein-Wiele, MD ; Andreas Mugge, MD ; Philipp Kahlert, MD2; ¨ 2 and Raimund Erbel, MD 1
Cardiovascular Center, St. Josef Hospital, Ruhr-University Bochum, Germany. 2Department of Cardiology, West-German Heart Center Essen, University of Duisburg- Essen, Germany. 3 Department of Cardiology, University of Witten-Herdecke, Germany. ^
^
Purpose: To prospectively assess the safety and efficacy of a novel absorbable vascular closure device (ExoSeal) in patients undergoing cardiac catheterization with femoral access compared to the established collagen-based (Angio-Seal) and suture-mediated (ProGlide) closure devices. Methods: This prospective, observational, dual-center, non-randomized, non-blinded study enrolled 1013 patients (65.1611.8 years) undergoing cardiac catheterization via a common femoral artery access in which hemostasis was achieved using a vascular closure device (255 Angio-Seal, 258 ProGlide, and 500 ExoSeal). In hospital complications (bleeding, hematoma, pseudoaneurysm, vessel occlusion, dissection, and arteriovenous fistula) of the puncture site and device failures (persistent bleeding) were recorded and compared for ExoSeal vs. the established devices (Angio-Seal þ ProGlide). Results: There were more complications after utilization of ExoSeal compared to established devices (3.6% vs. 1.2%, p¼0.012). No significant difference was observed in the device success rate between the established vascular closure devices (96.3%) and the novel device (94.8%, p¼0.28). Considering each closure system, Angio-Seal had the lowest complication rate (0.4%) and the highest efficacy (99.2%); the latter differed significantly from ExoSeal (94.8%, p¼0.001). Logistic regression analysis revealed a .3-fold odds of complications when using ExoSeal, which remained unchanged in multivariate analysis. Conclusion: Utilization of the novel vascular closure device is associated with a higher complication rate and a similar device failure rate compared to collagen-based and suturemediated devices, with Angio-Seal having the lowest complication and device failure rates. J Endovasc Ther. 2014;21:822–828 Key words: vascular closure devices, femoral artery access, vascular access, hemostasis, complications, collagen-based closure device, suture-mediated closure device, absorbable plug ^ ^
Vascular complications at the puncture site are still the most frequent complications in interventional cardiology and are associated with increased morbidity and mortality.1–3
The 1-year mortality in patients with vascular complications at the puncture site is 7.5% compared to 1.1% for those without complications.4 Moreover, most of the complications
The authors declare no association with any individual, company, or organization having a vested interest in the subject matter/products mentioned in this article. Corresponding author: Kaffer Kara, MD, Cardiovascular Center, St. Josef Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany. E-mail: [email protected] Q 2014 INTERNATIONAL SOCIETY
OF
ENDOVASCULAR SPECIALISTS
doi:10.1583/14-4744MR.1
Available at www.jevt.org
J ENDOVASC THER 2014;21:822–828
COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
at the puncture site require additional treatment, such as manual compression, transfusion, and transcatheter or surgical therapy. These are associated with further patient discomfort and extended hospital stay. Vascular closure devices (VCD) are well established in percutaneous diagnostic and therapeutic procedures. Over more than 20 years of experience, many studies and metaanalyses have documented the safety and effectiveness of VCDs in patients undergoing transfemoral catheterization.5–9 The risk of complications is not increased compared to manual compression, which is still the gold standard to achieve hemostasis at the puncture site. The most common types of VCD are collagen-based followed by suture-mediated.10 Recently, a novel vascular closure device with an absorbable plug has been developed. The synthetic polyglycolic acid plug is placed extravascularly without impeding the arterial blood flow; it is completely absorbed within 60 to 90 days. Major benefits of this new absorbable advice are its deployment through the existing procedure sheath without the need for sheath exchange and the avoidance of material in the vessel lumen. There is a lack of large prospective studies investigating the safety profile of this new absorbable VCD compared to the established VCDs. Therefore, the aim of this prospective observational study was to assess the efficacy and safety of a new absorbable VCD compared to individual collagen-based and suture-mediated VCDs in patients undergoing transfemoral cardiac catheterization.
METHODS Study Design This study was a prospective, observational, dual center, non-randomized analysis of consecutive patients undergoing coronary catheterization for diagnostic or therapeutic procedures via a 6-F transfemoral sheath. Indications for coronary angiography included acute coronary syndrome, known stenosis of one coronary artery, positive stress-testing, typical angina combined with extended risk factor profile, or other indication including
823
patients staged for kidney or liver transplantation. According to the study protocol, the participating physician was to use any of the 3 study VCDs (6-F only) at his/her discretion to close the femoral artery puncture without giving preference to any VCD in special situations. A VCD was not used if the puncture was through the posterior wall, if there were multiple punctures, or if a VCD at the puncture site had been used within the last 90 days. Patients did not receive a VCD if fibrinolytic drugs were given. Only experienced personnel performed the femoral artery puncture and closure device deployment. Participating physicians had experience of at least 500 transfemoral catheterizations and at least 50 cases with each VCD. Moreover, physicians using the novel VCD had been previously certified by the manufacturer. The examiners periodically reviewed the number of each utilized VCD to achieve a homogeneous application of the devices. After deployment of the VCD, the physician filled out a data entry form indicating the device type and size, duration of the deployment procedure, deployment success or failure (and cause), and any patient discomfort. Within 6 hours and before discharge, a physician examined the puncture site and completed another data entry form regarding the examination. If there was any complication, dedicated study personnel were called to record the event and monitor any necessary procedure or treatment (e.g., pictures were taken of any hematoma).
Study Devices The ExoSeal VCD (Cordis Corporation, Bridgewater, NJ, USA) is a novel device that seals the puncture with a plug applied on the outside of the vessel wall, without impeding blood flow because no material remains inside the artery. The plug consists of synthetic polyglycolic acid that is fully reabsorbed within 60 to 90 days. The VCD is placed though the existing procedure sheath over a nitinol indicator wire with a visual display on the handle; a pulsatile bleed-back indicator shows the correct position of the plug when it
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COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
leaves the artery and is placed on the extravascular surface of the femoral artery access site in the puncture channel. Hemostasis is achieved after 2 minutes of manual compression. More details on device deployment can be found elsewhere.11,12 The Angio-Seal device (St. Jude Medical, St. Paul, MN, USA) consists of an absorbable intraluminal component (‘‘anchor’’) and a small collagen plug.13–17 After sheath exchange, the anchor is deployed intraluminally such that the arterial wall and the arteriotomy site are ‘‘sandwiched’’ between the anchor and the collagen plug, inducing hemostasis. The ProGlide VCD (Abbott Vascular, Abbott Park, IL, USA) is a suture-mediated closure system utilizing a single monofilament polypropylene suture. This device is composed of a plunger, handle, guide, and a sheath. After sheath exchange, the needles are placed around the puncture site and a suture loop is formatted by depressing a plunger on the device. The device is then removed, leaving behind the suture tails. A knot is tied and pushed toward the arteriotomy to achieve hemostasis.17–19
VCD Technique After administration of local anesthetic using a 23-G Terumo spinal needle, the femoral artery (usually the right) was palpated using the bony landmarks of the iliac crest and the symphysis. If the anatomy was uncertain (e.g., in obese patients), fluoroscopy was performed to locate the femoral head. The 18-G needle was advanced toward the artery until the spurt of pulsatile blood was seen (no ultrasound guidance is used in our clinical practice). This was followed by the introduction of a guidewire, which is advanced gently into the artery (modified Seldinger technique). After removal of the puncture needle, a 6-F sheath was inserted. For diagnostic procedures, patients received 2500 units of unfractionated heparin; in therapeutic procedures, 7500 to 10,000 (weightadjusted) units of unfractionated heparin were administered during the intervention. After the procedure, the VCD was applied according the instructors for use of each device. No
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additional compression bandages were used in any case. Following the intervention, patients were supine for 6 hours. They were examined for access site complications with inspection of the puncture within 6 hours and before discharge. If any complication occurred, the subsequent procedures were recorded in detail. When no complications were noted, patients were discharged home with instructions to report immediately any swelling, hematoma, or pain.
Definitions and Data Capture Device failure after utilization of the VCD was defined as persistent bleeding requiring subsequent manual compression until hemostasis was achieved and the use of a compression bandage for 24 hours. In-hospital complications included bleeding, hematoma, pseudoaneurysm, vessel occlusion, dissection, and arteriovenous fistula. Complications were divided into major and minor as defined in previously published studies.19 Major complications were those requiring any endovascular or surgical intervention. Bleeding requiring transfusion or decreasing hemoglobin .2 g/dL was also considered a major complication. Moreover, hospitalization extended because of any puncture site complication was also recorded as a major complication. Minor complications included any observed events not requiring an intervention or increasing the hospital length of stay. Hematomas .3 cm in diameter were considered minor complications when no intervention was necessary. Patient age, sex, and traditional risk factors (diabetes, hypertension, hyperlipidemia, obesity, and history of smoking) were systematically recorded. Diabetes and hyperlipidemia were defined by a history of or being on medical treatment for the disease or first diagnosis during the hospital stay. Hypertension was defined as systolic blood pressure .140 mmHg or diastolic blood pressure .90 mmHg measured several times or intake of antihypertensive medication. Smoking was classified as current, former, or no history of smoking. Moreover, the antiplatelet or anticoagulation regimen was documented.
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COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
825
^
^ TABLE 1 Patient Characteristics Overall (n¼1013)
Angio-Seal þ ProGlide (n¼513)
ExoSeal (n¼500)
p
65.1611.8 704 (69.5%) 285 (28.1%) 924 (91.2%) 264 (26.1%) 760 (75.0%) 148 (14.6%) 170 (16.8%)
65.4611.7 376 (73.3%) 167 (32.6%) 484 (94.3%) 144 (28.1%) 398 (77.6%) 76 (14.8%) 89 (17.3%)
65.0611.9 328 (65.6%) 118 (23.6%) 440 (88.0%) 120 (24.0%) 362 (72.4%) 72 (14.4%) 81 (16.2%)
0.81 0.008 0.002 ,0.0001 0.145 0.057 0.87
430 446 137 450
212 249 52 270
218 197 85 180
Age, y Men Obesity Hypertension Diabetes Hyperlipidemia Smoking Former Antiplatelet therapy Single Dual None Therapeutic procedure
(42.4%) (44.0%) (13.5%) (44.4%)
(41.3%) (48.5%) (10.1%) (52.6%)
(43.6%) (39.4%) (17.0%) (35.9%)
0.009
,0.0001
^
^ Continuous data are presented as the means 6 standard deviation; categorical data are given as the counts/sample (percentage).
RESULTS
Statistical Analysis Patient characteristics are presented as mean 6 standard deviation for continuous variables and as count (percentage) for dichotomous traits. Data were analyzed for ExoSeal vs. the established VCDs (AngioSeal þ ProGlide). Differences in complication rates between these groups were explored using the Fisher exact test. Logistic regression analysis was used to determine an association between ExoSeal and complications. Multivariable analysis included the following variables: age, gender, obesity, hypertension, smoking, hyperlipidemia, diabetes, and therapeutic procedure. P,0.05 indicated statistical significance. All computations were performed using SPSS software (version 20.0; IBM Corporation, Somers, NY, USA).
From 2012 to 2013, 1013 patients (704 men; mean age 65.1611.8 years) were enrolled in this study. Of the performed procedures (255 Angio-Seal, 258 ProGlide, 500 ExoSeal), 563 were diagnostic and 450 were therapeutic. Patient details are shown in Table 1. In the total cohort, 24 (2.4%) complications were observed (Table 2): 18 (1.8%) minor and 6 (0.6%) major. In all, 18 hematomas (13 ExoSeal, 4 ProGlide, and 1 Angio-Seal) were classified as minor complications. One ExoSeal patient had a hematoma with a decrease in hemoglobin .2 g/dL. In 3 patients with increasing hematoma, manual compression and compression bandage were necessary, delaying hospital discharge (2 ExoSeal and 1 ProGlide). A pseudoaneurysm was observed in 1 ExoSeal patient and an arteriovenous fistula in another.
^
^ TABLE 2 Complication and Device Failure Rates for Each Vascular Closure Device Angio-Seal (n¼255) Complications Major Minor Device failure
^
1 0 1 2
(0.4%) (0%) (0.4%) (0.8%)
ProGlide (n¼258) 5 1 4 17
(1.9%) (0.4%) (1.6%) (6.6%)
ExoSeal (n¼500) 18 5 13 26
(3.6%) (1.0%) (2.6%) (5.2%)
Total (n¼1013) 24 6 18 45
(2.4%) (0.6%) (1.8%) (4.4%)
^
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COMPARISON OF VASCULAR CLOSURE DEVICES Kara et al.
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^
^ TABLE 3 Complication Rate of Each Vascular Closure Device Stratified by Procedure Type
Diagnostic procedures Therapeutic procedures
Angio-Seal
ProGlide
ExoSeal
1/150 (0.7%) 0/105 (0%)
1/93 (1.1%) 4/165 (2.4%)
6/320 (1.9%) 12/180 (6.7%)
^
^
There was a significantly higher complication rate after utilizing the ExoSeal compared to the established VCDs (3.6% vs. 1.2%, p¼0.012). Considering each VCD separately, there were higher complication rates with the ExoSeal compared to the Angio-Seal (3.6% vs. 0.4%, p¼0.004) and the ProGlide (3.6% vs. 1.6%, p¼0.148), though the latter was not statistically significant. This trend was also seen for minor and major complications, again not reaching statistical significance due to the small numbers of complications in each group. Table 3 shows the complication rate of each VCD stratified for diagnostic and therapeutic procedures. In logistic regression, the application of the ExoSeal was associated with a .3-fold increased risk of complications (Table 4). The incidence of complications did not decline with growing ExoSeal experience (3 in January-June 2012, 2 in July-December 2012, 9 in January-June 2013, and 4 in July-December 2013). Overall device failure occurred in 45 (4.4%) patients, and hemostasis was achieved by manual compression and compression bandage (Table 2). Therefore, overall device success was 95.6%. There was no significant difference in success rates between the established VCDs (96.3%) and the novel VCD (94.8%, p¼0.28). Considering each VCD, Angio-Seal (0.8%) had lowest device failure
followed by ExoSeal (5.2%) and ProGlide (6.6%), with significant differences for AngioSeal vs. ProGlide (p,0.001) and Angio-Seal vs. ExoSeal (p,0.0001). In logistic regression analysis, the use of ExoSeal was not associated with greater device failure (Table 4).
DISCUSSION This prospective study compared the safety and effectiveness of established VCDs (AngioSeal and ProGlide) with a novel VCD (ExoSeal) after diagnostic and therapeutic cardiac catheterization using a 6-F sheath. There were 3 times as many complications after ExoSeal than the established VCDs. Device failure rates were not significantly different between the groups. Considering each VCD, AngioSeal had the fewest complications and the highest efficacy rate. A notable strength of our study was the excellent experience of the operators with VCDs and the high number of patients enrolled. Most recently executed studies and registries found improving safety profiles for VCDs compared to manual compression2,20 after transfemoral cardiac catheterization. The largest published registry to date, which included 1,861,566 patients, demonstrated good performance of VCDs compared to manual compression in patients undergoing percuta-
^
^ TABLE 4 Logistic Regression Analyses of Complications and Device Failure for the ExoSeal Compared to the Established Vascular Closure Devices Complications
Device Failure
Model
Odds Ratio (95% CI)
p
Odds Ratio (95% CI)
p
Unadjusted Multivariate*
3.16 (1.25 to 8.03) 3.21 (1.20 to 8.37)
0.016 0.017
1.43 (0.78 to 2.62) 1.42 (0.75 to 2.67)
0.25 0.28
^
^ * Adjusted for age, gender, obesity, hypertension, smoking, hyperlipidemia, diabetes, and therapeutic procedure. CI: confidence interval.
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neous coronary interventions.18 The utilization of Angio-Seal or ProGlide reduced the vascular complication rate by .30%.20 This escalating performance profile for VCDs may be explained partly by the increasing technical development of the devices (less cumbersome) and the growing experience in handling them. Both the collagen-based and the suturemediated VCDs affect the lumen of the vessel, which may be a source of complications (e.g., vessel occlusion).13 Therefore, a VCD such as ExoSeal, which does not remain in the vessel lumen, could further reduce complications. Moreover, frequent sheath exchanges, which are necessary with the established VCDs but not with the ExoSeal, may be a source of complications.21 These positive features of ExoSeal could be major benefits of this new absorbable device. The first randomized trial (ECLIPSE: Ensure’s Vascular Closure Device Speeds Hemostasis) compared the performance of ExoSeal to manual compression in patients undergoing coronary or peripheral procedures.12 This study showed more vascular complications at the puncture site in the ExoSeal group (8.5% vs. 4.0%) for the secondary safety composite endpoint, but the difference was not statistically significant (p¼0.14). Another retrospective single-center analysis reported low complication rates (1.2%) for the use of the novel VCD in diagnostic and interventional procedures.11 To the best of our knowledge, no other prospective study has compared the safety and efficacy of this novel VCD against established closure systems. However, despite the previously described features suggesting improved safety profiles with the ExoSeal, we saw significantly higher complication rates with the novel VCD compared to the established devices. It has to be acknowledged that the complication rate of ExoSeal, though higher than the comparator group in our cohort, was still moderate. The low complication rate of Angio-Seal þ ProGlide as described in our study is comparable to previously published data.6,7,17,20 There was no significant difference in device failure for ExoSeal compared to the established VCDs. The observed low device
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failure rate for Angio-Seal and higher rate for ProGlide are known from previously published data.20
Limitations A major limitation of this study was the lack of randomization. Hence, the groups were not well matched in all aspects. In the Angio-Seal þ ProGlide group, hypertension, obesity, therapeutic procedures, and male patients were more frequent; moreover, more patients received dual antiplatelet therapy. Although therapeutic procedures and more intensive antiplatelet therapy are known risk factors for complications, the complication rate was higher for the ExoSeal group despite the group’s lower frequency of interventions.22 Another limitation of this study is that Angio-Seal was introduced .20 years ago and there is a lot of experience with this device. It might be possible that with increasing technical development of the ExoSeal and the growing experience in handling the new device, the complication rates will be reduced in future.
Conclusion Utilization of the ExoSeal is associated with higher complication rates compared to collagen-based (Angio-Seal) and suture-mediated (ProGlide) VCDs, with the Angio-Seal having the lowest complication and device failure rates.
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