Comparison Between Radial Approach and Femoral Approach With Vascular Closure Devices on the Occurrence of Access-Site Complications and Periprocedural Bleeding After Percutaneous Coronary Procedures: A Systematic Review and Meta-Analysis
Abstract: Objectives. Periprocedural bleedings, often related to vascular access site, represent an important drawback of percutaneous coronary procedures and are associated with worse outcomes. Radial access (RA) and, potentially, femoral access (FA) with vascular closure device (VCD) are useful strategies in order to mitigate periprocedural bleedings; nevertheless, their relative efficacy is largely undetermined. We aimed to perform a systematic review and meta-analysis of available studies comparing the efficacy of RA and FA with hemostasis by VCD (FA + VCD) on the reduction of access-site complications and/or periprocedural bleedings. Methods. Published studies reporting outcomes on access-site complications and periprocedural bleedings were included in the analysis. Data were extracted by two independent reviewers; odds ratio (OR) and 95% confidence interval (CI) were calculated by random-effects model and were used as summary statistics. Results. We included in the analysis 13 studies, of which 5 were randomized. Access-site complications were reported by 11 studies, amounting to 157,031 patients (77,713 in the RA group and 79,318 in the FA + VCD group), whereas periprocedural bleedings were reported by 12 studies, amounting to 600,196 patients (137,277 in the RA group and 462,919 in the FA + VCD group). RA was associated with a significant reduction in access-site complications (OR, 0.25; 95% CI ,0.21-0.31; P<.001) and periprocedural bleedings (OR, 0.40; 95% CI, 0.34-0.48; P<.001) as compared with FA + VCD; the results were consistent among randomized and observational studies. Conclusions. This meta-analysis shows that RA is superior to FA + VCD in the reduction of access-site complications and periprocedural bleedings.
J INVASIVE CARDIOL 2016;28(12):473-479. Epub 2016 September 15.
Key words: transradial approach, vascular closure devices, vascular complications, bleeding
Access-site complications and periprocedural bleedings represent a relevant issue in patients undergoing percutaneous coronary procedures and may adversely impact both in-hospital and long-term prognoses.1,2 Therefore, several bleeding avoidance strategies have been developed, such as radial approach (RA), the use of anticoagulant drugs with better safety profile,3-5 and potentially, the use of vascular closure devices (VCD) intended to achieve faster and possibly safer closure of the arteriotomy after procedures performed through femoral approach (FA).
According to pooled evidence coming from randomized studies, RA is more effective in reducing access-site complications and bleedings as compared with FA;6,7 similarly, data coming from both large registries and randomized trials suggest that the use of VCD for hemostasis following FA (FA + VCD) is associated with a significant reduction in access-site complications and bleedings vs FA with manual hemostasis.8-10
Nevertheless, evidence about the efficacy of RA as compared with FA + VCD is limited since only small, unpowered, randomized studies have been performed to date. Moreover, in many countries, FA with or without VCD is still the predominant approach to percutaneous coronary procedures. We conducted a systematic review and meta-analysis of both randomized and observational studies comparing RA with FA + VCD in patients undergoing PCI, focusing on access-site complications and periprocedural bleedings.
Methods
This meta-analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist.11 We searched major electronic databases (Medline, Scopus, Web of Science, and the Cochrane Library) through October 15, 2015. Medical subject headings and key words included the terms “(trans)radial,” “vascular access,” “(trans)femoral,” “coronary,” and “closure devices.” The reference section of selected papers and the “similar articles” section of PubMed were also searched.
Study selection. We adopted the following inclusion criteria: (1) full-text articles published in English; (2) studies comparing RA and FA with intended achievement of hemostasis by VCD in patients undergoing both diagnostic coronary angiography and/or percutaneous coronary intervention (PCI); and (3) studies reporting outcome data on access-site complications, periprocedural bleeding events, or both.
Outcomes. The study endpoints were: (1) access-site complications; and (2) periprocedural bleedings. The events relative to both endpoints were adjudicated according to the definitions adopted by each study. Access-site complications included hematoma, pseudoaneurysm, arteriovenous fistula, blood transfusion, surgical repair, and retroperitoneal hemorrhage; periprocedural bleedings included major bleedings, bleedings prolonging hospital stay, and non-access related bleedings in some studies (Table 1).
Data extraction and quality assessment. All relevant studies were independently extracted and reviewed by two investigators (SR and AS) who recorded outcome information on a standard Excel spreadsheet; any disagreement was resolved by consensus. The quality of studies was assessed by the Cochrane Collaboration’s tool for randomized studies and by the Newcastle Ottawa scale for non-randomized studies, respectively.12 Briefly, the Newcastle Ottawa scale for cohort studies assesses three areas of study quality: selection (four criteria), comparability (one criterion), and outcome (three criteria). A study can be awarded a maximum of 1 star for each numbered item within the selection and outcome categories. A maximum of 2 stars can be given for comparability. Scores can range from 0 (poor quality) to 9 (excellent quality).
Data analysis. Summary statistics were calculated by the Mantel-Haenszel method. Odds ratio (OR) and 95% confidence interval (CI) were calculated for dichotomous outcomes. The heterogeneity of the studies was analyzed using a chi-square test, for which a P-value <.20 was considered potentially heterogeneous. An I2 test of heterogeneity, which describes the percentage of total variation across studies that is due to heterogeneity, was also performed for every comparison. Heterogeneity is described as low, moderate, and high, based on I2 values of 25%, 50%, and 75%, respectively.
We used fixed-effects or random-effects models to produce across-study summary OR with 95% CIs. The random-effects estimate was preferentially used when statistical heterogeneity was observed. A 2-tailed P-value of <.05 was considered statistically significant. The potential for publication bias (ie, the likelihood of small studies with positive results being selectively published) was assessed by visual inspection of funnel plots, in which the treatment effect (OR) is plotted on the horizontal axis and the study weight (standard error of the OR) is plotted on the vertical axis; presence of asymmetry suggests possible publication bias. All statistical calculations were performed using Review Manager Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).
Results
We assessed for eligibility 119 records, 106 of which were excluded for being duplicates, not being relevant to the analysis, or not meeting inclusion criteria (Figure 1). Finally, 13 studies, of which 5 were randomized14,16,19-21 and 8 were observational,13,15,17,18,22-25 were included in the analysis (Table 1). All randomized studies, except the RIVAL (Radial Versus Femoral Access for Coronary Intervention) trial,21 were of small size. In the RIVAL study, the selection of vascular access (RA vs FA) was randomized, whereas femoral hemostasis technique was left to the discretion of treating physicians; femoral VCDs were used in 900 patients (25.6%) and data on non-coronary artery bypass graft (CABG) related major bleeding in this cohort as compared to the overall RA arm were included in the meta-analysis. Concerning observational studies, most data came from the National Cardiovascular Data Registry (NCDR)22 and from the British Cardiovascular Intervention Society (BCIS) database.24 The first one reported periprocedural bleedings within 72 hours of PCI in a large cohort of patients grouped according to access site used for PCI and type of anticoagulant (bivalirudin or heparin), whereas the latter reported access-site complications and bleedings in 2 propensity-matched cohorts of patients undergoing PCI through RA or FA + VCD, respectively. Concerning the NCDR, we focused on the outcomes relative to access-site related bleedings in patients receiving bivalirudin and treated either by RA or FA + VCD.
Main clinical characteristics, such as age, gender, body mass index, and prevalence of acute coronary syndrome, were not statistically different between the RA and FA + VCD groups across the majority of included studies; differently, the rate of glycoprotein IIb/IIIa blocker use was significantly higher in the RA group vs the FA + VCD group in 3 studies (Table 1).
Some studies included a particular subset of patients deemed at high risk of periprocedural bleeding, such as obese patients,17 fully anticoagulated patients,19 and end-stage liver disease patients.23
A suture-mediated closure device (Perclose, Abbott Vascular) and a collagen-based device (AngioSeal, St. Jude Medical) were used in the majority of studies; a nitinol clip-based device (Starclose, Abbott Vascular) was used in 3 studies, whereas a sandwich-type device (FemoSeal, St. Jude Medical) was used in 1 study. Data about the type of VCD were not reported either by the BCIS registry or by the CathPCI registry.
Eleven studies, of which 4 were randomized and 7 were observational, reported data on access-site complications, amounting to 157,031 patients (77,713 in the RA group and 79,318 in the FA + VCD group), whereas 12 studies (5 randomized and 7 observational) reported data on periprocedural bleedings, amounting to 600,196 patients (137,277 in the RA group and 462,919 in the FA + VCD group).
Access-site complications. In randomized studies, there were 8 events in 210 patients undergoing RA (3.8%) and 31 events in 222 patients undergoing FA + VCD (14.0%), with an OR of 0.19 (95% CI, 0.03-0.93; P=.04) favoring RA. In observational studies, there were 113 events in 77,503 patients undergoing RA (0.15%) and 503 events in 79,096 patients undergoing FA + VCD (0.64%), with an OR of 0.24 (95% CI, 0.20-0.30; P<.001) favoring RA. Overall, RA was associated with a significantly lower incidence of access-site complications vs FA + VCD (OR, 0.25; 95% CI, 0.21-0.31; P<.001). According to Chi-square test for subgroup differences, results were consistent between randomized and observational studies (Figure 2). We also performed a sensitivity analysis including only high-quality studies, ie, randomized studies fulfilling the Cochrane Collaboration’s tool for assessing the risk of bias and high-quality observational studies based on a Newcastle Ottawa Scale score of ≥7. This analysis yielded similar results, with an OR of 0.25 (0.20-0.30; P<.01) favoring RA. Visual inspection of inverted funnel plot did not suggest a significant publication bias.
Periprocedural bleedings. In randomized studies, there were 28 events in 3717 patients undergoing RA (0.75%) and 27 events in 1122 patients undergoing FA + VCD (2.41%), with an OR of 0.41 (95% CI, 0.13-1.30; P=.13). In observational studies, there were 297 events in 133,560 patients undergoing RA (0.22%) and 2621 events in 461,797 patients undergoing FA+VCD (0.57%), with an OR of 0.39 (95% CI, 0.34-0.44; P<.001). Overall, RA was associated with a significantly lower incidence of periprocedural bleedings vs FA + VCD (OR, 0.40; 95% CI, 0.34-0.48; P<.001). According to Chi-square test for subgroup differences, results were consistent between randomized and observational studies (Figure 3). Similar results were observed in a sensitivity analysis including high-quality studies (OR, 0.39; 95% CI, 0.34-0.44; P<.01). Visual inspection of inverted funnel plot did not suggest a significant publication bias.
Discussion
This meta-analysis shows that RA, as compared to FA with achievement of hemostasis by using VCD, is associated with a significant reduction in the occurrence of both access-site complications and periprocedural bleedings in patients undergoing diagnostic and interventional percutaneous coronary procedures. Given the costs and potential complications associated with VCD use, these data suggest that RA should be the preferred bleeding avoidance strategy in patients undergoing percutaneous coronary procedures.
Periprocedural bleedings, both access-site related and non-access-site related, are associated with an increased risk of in-hospital and long-term adverse events in patients undergoing PCI.26,27 Therefore, several bleeding avoidance strategies, including bivalirudin, radial approach, and VCDs, have been proposed in order to improve periprocedural safety and long-term outcomes; the implementation of these strategies, indeed, was found to be effective in reducing bleedings, particularly in high-risk patients, in large registries.28,29
The superiority of RA vs FA in the reduction on non-CABG related major bleedings (Bleeding Academic Research Consortium [BARC] 3 and 5) was recently confirmed by the MATRIX Access (Minimizing Adverse Haemorragic Events by Transradial Access Site and Systemic Implementation of angioX) trial, which enrolled patients with acute coronary syndrome undergoing an invasive strategy.30 On the other hand, strong evidence supporting the use of VCDs in order to reduce access-site complications and bleedings is lacking. Indeed, several meta-analyses failed to show a significant benefit of VCDs in reducing femoral access-site complications and bleedings vs manual hemostasis; actually, the risk of some adverse events, such as groin infection, was even greater with VCDs.31,32
Nevertheless, a recent large, randomized trial in patients undergoing coronary angiography demonstrated that VCDs are non-inferior to manual compression with respect to procedure complications33 and observational data coming from a large registry showed that VCDs were associated with a reduction in vascular complications and transfusions, but also with an increased risk of retroperitoneal bleeding, as compared with manual hemostasis;8 moreover, other drawbacks of VCDs include their cost and possible increase in bleeding risk in the case of device failure in fully anticoagulated patients, such as at the end of a PCI procedure. Notwithstanding these limitations, VCDs are considered to be an effective bleeding avoidance strategy, especially in countries where FA represents the preferred access route for coronary procedures.34
The relative efficacy of RA as compared with FA + VCD in the prevention of access-site complications and periprocedural bleeding is largely undetermined, since it was only assessed in small, unpowered randomized trials. Our meta-analysis, to the best of our knowledge, is the first one to pool available data from randomized and observational studies aiming to compare RA with FA + VCD in the reduction of access-site complications and periprocedural bleedings.
Study limitations. Our study suffers from several limitations, such as the inclusion of mainly observational data, likely affected by a selection bias, and the heterogeneous definitions of periprocedural bleedings adopted across different studies (Table 1). Indeed, although many studies focused on access-site bleedings, other studies also included non-access site bleedings; moreover, different criteria for the definition of severe, major bleedings were also adopted; finally, accurate adjudication of events was limited in many studies by the retrospective design.
Heterogeneity in the definition of bleeding events was shown to significantly affect their impact on adverse outcomes, such as death and myocardial infarction.35 This led the BARC to develop a standardized bleeding endpoint definition in order to optimally adjudicate the events and to better interpret relative safety comparisons of different therapeutic strategies;36 however, none of the studies included in this meta-analysis adopted the BARC classification.
Another debated issue is represented by radial artery occlusion, which may follow transradial procedures with a reported incidence between 0.8% and 30%.37 This event was not adjudicated as an access-site complication in most studies included in our meta-analysis as well as in large trials comparing RA with FA.21,30 The underreporting of this event arises from the fact that, in most cases, radial artery occlusion is asymptomatic due to blood supply to the hand from the ulnar artery and, to a lesser extent, from the interosseous artery; indeed, hand strength in patients with radial artery occlusion after coronary procedures was not reduced as compared with baseline values.38 Nevertheless, radial artery occlusion may be clinically relevant since it may jeopardize further use of the artery for future procedures, bypass grafting, and hemodialysis fistula;39 therefore, it should represent an endpoint of interest for future studies.
Conclusion
This meta-analysis suggests that RA is a more effective strategy for reducing access-site complications and periprocedural bleedings as compared with FA + VCD.
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From the 1Interventional Cardiology Unit and Emergency Department, Sandro Pertini Hospital, Rome, Italy; 2Department of Cardiology, University Hospital of North Staffordshire, Stoke-on-Trent, United Kingdom; 3Interventional Cardiology, Sant’Andrea Hospital, Rome, Italy; 4Cardiology Department, Western Health, Footscray Hospital, Australia; 5Medical University of Silesia, Silesian Center for Heart Diseases, Zabrze, Poland; 6University of Toledo Medical Center, Toledo, Ohio; 7Massy, Ramsay-Générale de Santé, France; and 8the Duke Clinical Research Institute, Durham, North Carolina.
Disclosure. The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rao reports consultant fees/honoraria from Terumo Interventional Systems, The Medicines Company, Medtronic, Merck, and Astra Zeneca. The remaining authors report no conflicts of interest regarding the contents herein.
Manuscript submitted April 22, 2016, final acceptance given July 5, 2016.
Address for correspondence: Dr Stefano Rigattieri, Interventional Cardiology Unit and Emergency Department, Sandro Pertini Hospital, Via dei Monti Tiburtini 385, 00157, Rome, Italy. Email: stefanorigattieri@yahoo.it
