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Commentary
Vascular Closure Devices: Is the Case Closed?
December 2010
Vascular hemostasis is a key issue for the successful completion of either diagnostic or interventional percutaneous endovascular procedures. Traditionally, mechanical compression, either manual or using one of the commercially available femoral compression devices (FemoStop or C-Clamp), followed by prolonged bed rest (4 to 8 hours), was considered the gold-standard technique for achieving hemostasis after transfemoral percutaneous coronary interventions (PCI). Labor-intensive practice, prolonged immobilization, and considerable patient discomfort are the known limitations of mechanical compression techniques prompting a search for advantageous solutions.
Vascular closure devices (VCDs) represent an alternative approach to achieve hemostasis after PCI. The benefits of earlier ambulation and shorter hospital stays have led to increasing use of VCDs in the past decade.
Access-related vascular complications differ widely from a small hematoma to serious potentially fatal complications associated with prolonged hospitalization and increased costs. The incidence of vascular complications using mechanical compression depends on patient- and procedure-related characteristics, as well as operator experience and the learning curve.1–3 Female gender, older age, either too low or excessive weight and the presence of peripheral arterial disease are well-recognized patient-related factors associated with increased vascular complications, while larger introducer sheath size, longer procedural length and excessive anticoagulation, along with inaccurate location of the arterial puncture site, are the procedural factors known to increase local complication risk.4,5 The changing profile of the population treated with percutaneous techniques towards more elderly and high-risk patients, as well as increasing intervention complexity and introduction of composite adjunctive antiplatelet/antithrombotic therapy, may potentially affect the overall complication rate.
In this issue of the Journal, Hermanides et al, on behalf of the Zwolle Myocardial Infarction Study Group, present the results of the randomized ANGIO-Seal or manual Compression After coRonary intervention Evaluation (ANGIOCARE) study in patients undergoing PCI carried out using 6 French introducer sheaths.6 Patient ambulation was performed 4 hours after using the Angio-Seal and 8 hours after using manual compression. The trial was powered to demonstrate a superiority for the Angio-Seal versus manual compression, and a prespecified primary endpoint was a composite of large (> 5 cm) hematoma at the puncture site, groin bleeding resulting in prolonged hospital stay or blood transfusion or formation of arteriovenous fistula with or without surgical intervention at the puncture site. The study did not meet its primary endpoint, showing no significant differences in rates of vascular complications in PCI-treated patients managed with Angio-Seal or manual compression. In other words, Angio-Seal demonstrated the same safety profile as manual hemostasis. Only in a subgroup of patients with hypertension, the use of Angio-Seal was associated with a significantly lower rate of major vascular complications. Secondary endpoints including a post-procedural change in hemoglobin values and the overall duration of hospitalization were similar in the two groups.
Angio-Seal was one of the first devices to effectively close arterial punctures, and was approved for marketing by the U.S. Food and Drug Administration in 1996. It is an intraluminal VCD that creates a mechanical seal by “sandwiching” the puncture site between a bioabsorbable anchor and purified bovine collagen sponge which dissolves within 8 to 12 weeks. Among numerous reports on the Angio-Seal, very few are well-designed randomized, controlled studies.7–11 The majority of publications are cohort and case-controlled studies and registries. While these studies in large, unselected populations define practice patterns and assess the overall incidence of complications, they have inherent limitations such as suboptimal data collection, lack of monitoring and/or the lack of an appropriate control arm.
The authors of the manuscript should therefore be acknowledged for conducting a large prospective, randomized trial comparing use of the Angio-Seal closure device with manual compression in the setting of contemporary PCI. How should the results of the ANGIOCARE study be interpreted? Being by design a prospective randomized, controlled trial aiming to provide the highest level of scientific evidence, this study is a valuable contribution to the current body of evidence on VCDs. However, there are a few limitations that should be considered in the interpretation of this study.
First, this was a single-center study; lower scientific weight is given to single-center versus multicenter trials.12,13 Second, the definitions of access site-related vascular complications comprising the prespecified primary endpoint may be debated. This limitation is not specific to the ANGIOCARE study solely. Enormous heterogeneity in defining complications is a distinctive feature of all studies assessing VCDs, leading to difficulties in the interpretation of the results. That is why despite the numerous studies on VCDs published as peer-review publications, no major conclusion has been reached yet with regard to their safety.
Unification of standard definitions of major bleeding and vascular complications is therefore absolutely necessary in order to critically assess the results of future trials on VCDs and to avoid heterogeneity in outcomes. Consensus endpoint definitions should be created for the standardized assessment of vascular complications in a similar way where the interventional cardiology society have achieved an agreement to standardize endpoint definitions for clinical trials by arranging an academic research consortium (ARC).14 This will undoubtedly improve design and quality of future randomized, controlled trials on VCDs and their meticulous appraisal. Third, the duration of follow up should not be limited to in-hospital stay and should be extended to 30 days. The rate of late local complications is low but not negligible. Optimally, also, the data regarding patients’ viewpoints on the use of Angio-Seal as compared with mechanical compression should have been collected. It might be one of the endpoints where an advantage in favor of VCDs would be demonstrated. Figure1 summarizes information to be collected in properly conducted randomized, controlled trials on VCDs, and Figure 2 summarizes the main criteria for the assessment of VCDs.
A finding of lower incidence of complications in the subgroup of patients with hypertension using Angio-Seal should be considered with care. The study was underpowered to reveal differences in the rare endpoints in this subgroup, and therefore this outcome should be viewed as hypothesis-generating rather than conclusive.
In the ANGIOCARE study, the use of femoral angiography as recommended by the Angio-Seal manufacturer has not been routinely performed. While subject for debate, we believe that an arteriogram preceding vascular closure is required to provide key information on the arterial puncture site in relation to the femoral artery bifurcation, inguinal ligament and femoral head, as well as the size of the femoral artery, presence of atherosclerotic disease and vascular calcification. Certain findings on the femoral angiogram including small (
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From Technion – Israel Institute of Technology and Rambam Health Care Campus, Haifa, Israel.
Address for correspondence: Eugenia Nikolsky, MD, PhD, Director, Cardiovascular Research Unit, Rambam Health Care Campus, Haifa, Israel. E-mail: e_nikolsky@rambam.health.gov.il ?
A finding of lower incidence of complications in the subgroup of patients with hypertension using Angio-Seal should be considered with care. The study was underpowered to reveal differences in the rare endpoints in this subgroup, and therefore this outcome should be viewed as hypothesis-generating rather than conclusive.
In the ANGIOCARE study, the use of femoral angiography as recommended by the Angio-Seal manufacturer has not been routinely performed. While subject for debate, we believe that an arteriogram preceding vascular closure is required to provide key information on the arterial puncture site in relation to the femoral artery bifurcation, inguinal ligament and femoral head, as well as the size of the femoral artery, presence of atherosclerotic disease and vascular calcification. Certain findings on the femoral angiogram including small (
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