The Safety and Efficacy of “Pre-closure” Utilizing the Closer™ Suture-mediated Vascular Closure Device for Achievement of Hemost

The Prostar^® XL (Perclose, Redwood City, California) allows the femoral arterial puncture site to be closed percutaneously with two nonabsorbable sutures. The Perclose AcceleRated Ambulation and DischargE (PARADISE) trial1 showed that use of the Prostar XL device, combined with the use of hydrochloride lidocaine containing 1% epinephrine as local anesthesia to reduce blood oozing from subcutaneous tissue, was a safe and effective means to achieve hemostasis and to improve time-to-ambulation and discharge after percutaneous coronary interventions (PCI). The Closer 6 Fr suture-mediated percutaneous vascular closure device, which is smaller than the 8–10 Fr Prostar XL, inserts easily into the artery without predilatation of subcutaneous tissue. In particular, the suture deployment technique prior to sheath insertion (pre-closure) allows the use of a larger sheath introducer than the size of the suture-mediated device because the diameter of suture capture with the Closer is larger than an 8 Fr hole. The Closer has been shown to be effective for closure of 6 Fr sheath punctures,^2,3 and a previous study4 showed that the pre-closure technique improved the time-to-hemostasis, ambulation and discharge compared to manual compression. The purpose of this study was to assess the safety and efficacy of the pre-closure technique using the Closer device in terms of time-to-hemostasis, ambulation and patient discharge. Methods Study patients. Between January and September 2001, the 6 Fr Closer device was used post-PCI in 153 consecutive patients. The inclusion criteria were: 1) patient age (range from 18 to 80 years old); 2) patients were not pregnant; 3) catheterization procedure was able to be performed from the femoral approach using a 7 or 8 Fr sheath; 4) patients would be able to leave the hospital within 24 hours post-PCI; and 5) patients were acceptable candidates for emergent vascular surgical repair. The exclusion criteria were: 1) patients with known platelet dysfunction or bleeding diathesis; 2) patients who were enrolled in other clinical trials; 3) patients requiring intraaortic balloon pump insertion; 4) patient with acute coronary syndrome; 5) patients who had received the collagen plug hemostasis device; 6) arterial sheath insertion at the profunda artery confirmed by angiography of the femoral artery; 7) clinical or ultrasound evidence of significant peripheral vascular disease, history of vascular surgery, absent pedal pulse, femoral artery bruit, hematoma, or pseudoaneurysm; and 8) patients who developed a hematoma during PCI. Eligible patients were invited to participate in this study and informed consent was obtained under a protocol approved by each institution’s ethics committee. Study procedure. Following artery access with an 18-gauge single-wall puncture needle, angiography of the femoral artery was performed before sheath insertion to confirm that the puncture was at the femoral artery segment that was straight and had no stenosis. In patients undergoing PCI with an 8 Fr sheath, the puncture needle was exchanged over the guide wire for the Closer 6 Fr. The device was positioned in the artery, the sutures deployed, and the device was removed over the wire with placement of the 8 Fr sheath. The sutures were tied after sheath removal (pre-closure arm). Patients undergoing PCI with a 7 Fr sheath remained in the laboratory on the catheterization table where the sheath was removed and the Closer device was deployed. Immediately following this, a final Clincher Knot was tied (standard arm). Hydrochloride lidocaine containing 1% epinephrine as local anesthesia was administered if a patient had pain at the puncture site follwing tying of the sutures. These procedures were performed using the manufacturer’s recommended technique. After the procedure, patients could sit on the catheterization table without hemorrhage or oozing from the puncture site. In cases where there was a small amount of oozing, post-procedure management called for an initial one-hour period of bed rest. Patients could elevate their head from 30 to 45 degrees and turn over leaving their access leg restrained. After about one hour, they were able to sit on the bed without bleeding or oozing from the puncture site and were able to walk after another one to two hours. Patients were discharged the following day unless cardiovascular and peripheral vascular complications were reported. Oral antibiotics were administed four days after the procedure in all patients. The use of anticoagulation agents such as heparin during PCI was confirmed at each site, and antithrombotic or anticoagulant agents were administered post-PCI. Use of such medications was recorded. Study endpoint and definitions. The primary endpoint was time-to-hospital discharge, which was calculated as the total time from the start of the hemostasis procedure until leaving the hospital. Secondary endpoints were time-to-procedure, time-to-hemostasis, time-to-ambulation (time-to-sitting and time-to-ambulation were noted, as was distance walked), the incidence of major complications at the femoral access site, and patient discomfort. In the pre-closure arm, time-to-procedure was defined as the total time elapsed from insertion of the Closer device to deployment of the percutaneous sutures before sheath insertion, and from removal of the guiding catheter until cutting the suture below skin level. Time-to-hemostasis was defined as the time elapsed from removal of the guiding catheter until hemostasis was achieved. In the standard arm, time-to-procedure was defined as the time elapsed from removal of the guiding catheter until cutting the sutures below skin level. Time-to-hemostasis was defined as the time elapsed from removal of the guiding catheter until hemostasis was achieved. Procedure success was defined as complete hemostasis achieved by the Closer with or without 5 minutes of adjunctive manual compression. Time-to-sitting was defined as the time elapsed from hemostasis to sitting on the bed without bleeding, and time-to-ambulation was defined as the time elapsed from hemostasis to walking without complications. Peripheral vascular complications were categorized as follows: 1) vascular surgical repair or ultrasound-guided compression for uncontrolled bleeding, large pseudoaneurysm, arteriovenous fistula, femoral artery occlusion due to thrombosis or dissection; 2) infection at the puncture site requiring intravenous antibiotics; 3) re-bleeding at the puncture site; 4) femoral nerve injury; 5) small pseudoaneurysm treated medically; and 6) hematoma (0.5 to 3 cm and > 3 cm). Activated clotting time (ACT) value was measured immediately after catheterization. Follow-up. Patients were examined serially until hospital discharge and then signs of femoral puncture site complication were confirmed by office examination or telephone follow-up at two to four weeks post-discharge. Data management and statistical analysis. Case report forms were completed at each institution. Categorical variables are expressed as frequencies and percentages, whereas continuous variables are expressed as mean value ± standard deviation when appropriate. Results Patient characteristics. Among 153 study patients, a total of 97 patients undergoing PCI with an 8 Fr sheath had percutaneous sutures deployed before sheath placement (pre-closure arm), while the other 56 patients had percutaneous sutures deployed immediately after sheath removal (standard arm). The clinical characteristics and laboratory data are summarized in Table 1. Time-to-procedure and hemostasis. Procedural variables and time-to-procedure and hemostasis are summarized in Table 2. The procedures were successful in 99% of patients in the pre-closure arm and in all patients in the standard arm. In the pre-closure arm, percutaneous sutures were deployed successfully deployed in one patient before sheath insertion, however, this patient experienced hemorrhaging from the puncture site after the sutures were tied, requiring 20 minutes of conventional manual compression. Additional local anesthesia containing 1% epinephrine was required in only 30% of patients, and no additional adjunctive compression was required in the pre-closure arm patients. In the standard arm, 73% of patients required additional local anesthesia due to pain at the puncture site, however, no patients required additional adjunctive compression. Thus, in both arms of this study, the time-to-procedure did not differ from the time-to-hemostasis. However, 22% of patients required adjunctive manual compression in the PARADISE trial, and the time-to-hemostasis was longer than the time-to-procedure in the PARADISE trial. Time-to-sitting and ambulation: The time-to-ambulation is summarized in Table 2. After hemostasis, patients in the pre-closure arm were able to sit up after a mean time of 1.4 ± 1.7 hours of bed rest, walking was possible after 3.6 ± 2.8 hours, and discharge was possible after 21.3 ± 3.4 hours. These results are comparable to those in the standard arm and the PARADISE trial. A total 19 patients (20%) in the pre-closure arm and 30 patients (53%) in the standard arm were able to sit up on the catheterization table without hemorrhage or oozing from the puncture site. A total 73 patients (75%) in the pre-closure arm and 49 patients (88%) in the standard arm were able to sit up within 1.5 hours. A total of 67 patients (69%) in the pre-closure arm and 46 patients (82%) in the standard arm were able to ambulate within 3.5 hours. Time-to-discharge. The time-to-discharge is indicated in Table 2. Within 24 hours, 92 (95%) of the pre-closure arm patients and 54 (96%) of the standard arm patients were discharged. No patients in the pre-closure arm remained hospitalized more two days following angioplasty, as compared to 1 (2%) patient in the standard arm and 3 (3%) patients in the PARADISE trial. Peripheral vascular complications. In this trial, the overall incidence of peripheral vascular complications was quite low despite full anticoagulation with a prolonged activated clotting time (Table 3). In the pre-closure arm, a 1.5 cm hematoma was present after one patient sat up, though his time-to-hemostasis was 4 minutes without additional local anesthesia or oozing. However, because his hematoma did not become large, he was discharged 16.2 hours after the procedure. In the standard arm, no major or minor complications were reported. To evaluate the incidence of delayed complications, puncture sites were confirmed by clinical examination or telephone follow-up two to four weeks after discharge. At follow-up examination, none of the patients in either arm of this study presented with major or minor complications. In the PARADISE trial, however, only one patient developed a small hematoma during hospitalization. At follow-up examination, one patient had developed a small hematoma. Another patient whose time-to-ambulation was 2.5 hours without oozing and who was discharged within 24 hours post-procedure, presented with an infection at the suture site that required surgical repair. Discussion There still remain situations that require the use of larger-sized sheaths, although the trend is to use smaller 6 Fr sheaths for the femoral approach. Directional coronary atherectomy catheters, large rotational atherectomy burrs and some brachytherapy systems are used over 8 Fr delivery catheters. In the PARADISE trial,¹ the Prostar XL device, combined with the use of hydrochloride lidocaine containing 1% epinephrine as local anesthesia, was able to reduce oozing from the tissue surrounding the puncture site and to shorten patients’ time-to-ambulation and discharge. However, 22% of patients in the PARADISE trial required adjunctive manual compression due to oozing from the puncture site, thus the time-to-hemostasis was longer than the time-to-procedure. The pre-closure technique utilizing the 6 Fr Closer device allows for the use of a sheath introducer that is larger than the size of the suture-mediated device because the diameter of suture capture with the Closer is larger than an 8 Fr hole. A previous study showed that the pre-closure technique using the Closer device reduced the time-to-hemostasis compared with manual compression.⁴ In this study, the time to hemostasis of the pre-closure arm was comparable to those of the other two groups without requiring additional manual compression. The results of this study suggest that the Closer device is a safe means to achieve hemostasis using larger sheaths without causing oozing from the puncture site. Following hemostasis, patients in the pre-closure arm were able to sit up after a mean time of 1.4 ± 1.7 hours of bed rest, ambulation was possible after 3.6 ± 2.8 hours, and discharge was possible after 21.3 ± 3.4 hours. These results are comparable to those in the standard arm of the present study and the PARADISE trial. Although the procedure and hemostasis were successfully completed, oozing of blood from subcutaneous tissue was persistent in the early ambulation and discharge patients in the EDEN trial.⁵ In the PARADISE trial, oozing from subcutaneous tissue at the puncture site was reduced by using hydrochloride lidocaine containing 1% epinephrine in all patients. However, because the 6 Fr Closer requires no skin incision before insertion of the device, the size was smaller than that of the Proster XL device. In this study, oozing of blood did not prolong the time-to-ambulation and discharge regardless of whether additional local anesthesia was used. Peripheral vascular complications after catheterization are associated with some risk factors such as larger sheath size and aggressive anticoagulation with or without closure devices.⁶ Furthermore, according to previsou reports,^7–10 the Prostar XL device has not significantly decreased major complications. Several reports^6,11–12 in the surgical literature suggest that percutaneous suture-mediated closure devices are associated with pseudoaneurysms not amenable to ultrasound compression therapy, greater loss of blood, the need for transfusions, and a higher incidence of groin infections compared with manual compression. The above-mentioned studies suggest that groin complications tend to appear later in patients on whom closure devices are used compared to those who receive manual compression, and that infections tend to occur more frequently in patients on whom closure devices are used. Oral antibiotics were administered to prevent infection four days post-procedure in all patients in this study and no major complication occurred prior to follow-up examination. In the PARADISE trial, full anesthesia and careful predilatation of subcutaneous tissue reduces the incidence of minor bleeding complications such as hematomas.¹ Very few patiens in this study experienced minor bleeding complications because the Closer device, which is smaller than earlier devices, requires no predilatation of subcutaneous tissue. Thus, the complication rates in this study are lower than those described in previous reports.^6,7Study limitations. This study has several important limitations. First, there were more patients enrolled in the pre-closure arm (n = 97) than in the standard arm (n = 56), leading to a potential bias. However, clinical characteristics did not differ significantly between the two arms. Secondly, although hydrochloride lidocaine containing 1% epinephrine as local anesthesia was used for all patients in the PARADISE trial to reduce oozing problems, it was used in 30% patients in the pre-closure arm and 73% in the standard arm. However, the Closer device eliminated the need for additional local anesthesia to reduce oozing of blood from the puncture site because it is smaller than the 8–10 Fr Prostar XL, and inserts easily into the artery without predilatation of subcutaneous tissue. Finally, although the enrollment of the study population was not randomized or prospective, we compared our patient data with those of the PARADISE trial which was published previously. The devices and the procedure for suture tying were different between these two studies. Thus, no definitive conclusions can be drawn from these retrospective comparisons regarding the relative efficacy of pre-closure versus standard closure techniques, nor from the Closer device versus the Prostar XL device. Conclusions The Closer suture-mediated percutaneous closure device appears to be a safe and rapid means of achieving hemostasis, ambulation and discharge. Moreover, the pre-closure technique appears to achieve hemostasis using a large-sized sheath post-PCI without causing major peripheral complications.

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