Radial Versus Femoral Access in Invasively Managed Patients With Acute Coronary Syndrome
Early invasive management and combined use of potent antithrombotic drugs have substantially reduced the risk for ischemic events in patients with acute coronary syndrome (ACS) but this came at the price of increased bleeding (1, 2) Major bleeding events are consistently recognized as important determinants of death and ischemia (3, 4) and strategies to avoid bleeding are key to improving the outcomes of patients with ACS who are invasively managed (5) Over the past 2 decades, the radial access site has been increasingly used as an alternative to the femoral access site for both diagnostic and interventional purposes; the main advantage of radial procedures is that they are associated with a lower incidence of vascular bleeding complications (68) Comparative trials conducted in patients with ACS have come to conflicting conclusions about the effect of the radial approach in reducing mortality and ischemic events on top of a consistent bleeding benefit (919) An earlier meta analysis conducted across the broad spectrum of percutaneous coronary interventions concluded that radial access reduces major bleeding with a corresponding trend for fewer ischemic events compared with femoral access (8) Three more meta analyses restricted to patients with ST segment elevation myocardial infarction (STEMI) (2022) and 1 article that included a meta analysis of ACS trials (19) concluded that radial access is associated with lower mortality and major bleeding. Of note, several older trials pooled in these meta analyses were single center, included a small number of patients, and were of lower methodological quality. Small trials, particularly when affected by substantial bias, tend to report greater treatment benefits than larger trials and may favor increased heterogeneity and distortion when included in meta analyses (23, 24) We conducted an updated systematic review and meta analysis that focused on large, high quality, contemporary randomized studies comparing radial and femoral access in invasively managed patients with ACS. Methods Protocol and Registration The protocol was registered in the PROSPERO database (CRD42015022031) and was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) standards (25) At the editors' request, this paper focuses on a random effects meta analysis of the higher quality large trials. Data Sources and Searches The full search string is reproduced in Appendix Table 1. MEDLINE, EMBASE, and Cochrane databases were searched for reports published from January 1990 through August 2015. Additional sources included www.clinicaltrials.gov, www.clinicaltrialresults.org, www.tctmd.com, www.cardiosource.com, www.theheart.org, www.escardio.org, Google Scholar, and abstracts or presentations from major cardiovascular meetings. We searched the reference lists of relevant studies and reviews, editorials, and letters to identify further citations. The most updated or inclusive data for a given study were chosen for abstraction. Appendix Table 1. Search String Study Selection We selected trials published in English or presented at a major cardiovascular meeting through August 2015 that met all the following inclusion criteria: 1) patients with ACS with intended percutaneous coronary intervention; 2) randomized, multicenter study of radial versus femoral access; and 3) study reporting procedural, in hospital, or 30 day outcomes. Data Extraction and Quality Assessment Two investigators independently identified studies, extracted data, and rated the risk of bias at the study level, as recommended by the Cochrane Collaboration (26) Studies deemed to be at low, unclear, and high risk of bias received 1, 0, and 1 point for each domain of the Cochrane tool, respectively. A low risk of bias was defined as a total score of 4 or higher. Conflicts were adjudicated by consensus. Study Outcomes The main outcome of interest was all cause death. Other outcomes included myocardial infarction, stroke, major adverse cardiovascular events (MACE) access site bleeding, and major bleeding. Procedural data (duration and crossover rates [that is, switch from radial to femoral in the radial group and from femoral to radial in the femoral group] were also explored. Data Synthesis and Analysis Meta analysis was limited to recent large, high quality trials. The results of those studies were combined by using a MantelHaenszel random effects model to account for heterogeneity between groups (27) The BiggerstaffTweedie (28) estimator was used to quantify the variation in the true effects of each study as expressed by the statistic. Results were also pooled in an additional analysis by using the method of DerSimonian and Laird (29) Overall estimates of effect for the comparison of radial versus femoral access were reported as relative risks (RRs) and 95% CIs for dichotomous outcomes and as standardized mean differences and 95% CIs for continuous outcomes. Statistical heterogeneity was assessed with Cochran Q statistics via a chi square test and was quantified by using the I 2 statistic; I 2 values less than 25% 25% to 50% and greater than 50% represented mild, moderate, and severe heterogeneity, respectively (30) A sensitivity analysis restricted to studies enrolling only patients with STEMI was performed. Egger regression asymmetry tests were used to explore the chance of publication bias. Statistical analyses were performed with Review Manager (Nordic Cochrane Centre, Cochrane Collaboration) Comprehensive Meta Analysis (Biostat) and Trial Sequential Analysis (Copenhagen Trial Unit, Rigshospitalet) software. Role of the Funding Source No external funding was received. Results The initial search identified 227 citations, of which 27 were retrieved for full text review. Seventeen of these met inclusion criteria (919, 3136) whereas 10 were nonrandomized or post hoc comparisons of vascular access sites from randomized trials of other interventions (Figure 1) Thirteen of the 17 eligible randomized trials (915, 3136) were small single center studies or were judged to be at high risk of bias and to contribute little information (Appendix Table 2) The 4 higher quality trials encompassed a total of 17133 patients (8552 randomly assigned to radial access and 8581 randomly assigned to femoral access) (1619) Figure 1. Summary of evidence search and selection. Selection process for studies to be included in the meta analysis in compliance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) standards. Appendix Table 2. Details of Randomized Trials of Radial Versus Femoral Access Excluded From Meta analysis Because of Their Single Center Design and/or Risk of Bias Tables 1 and 2 list key characteristics of these trials and related interventions. All were multicenter and included patients with ACS undergoing percutaneous coronary intervention. Two trialsRIFLE STEACS (Radial Versus Femoral Randomized Investigation in ST Elevation Acute Coronary Syndrome) (17) and STEMI RADIAL (Trial Comparing Radial and Femoral Approach in Primary Percutaneous Coronary Intervention) (18)included only patients with STEMI. All trials excluded patients with severe peripheral artery disease, and 2 trialsRIVAL (A Trial of Trans radial Versus Trans femoral Percutaneous Coronary Intervention Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy) (16) and STEMI RADIAL (18)excluded patients with cardiogenic shock. All trials mandated that providers have a minimum degree of proficiency in radial procedures. Although study quality was rated high overall, trials shared a risk of performance bias because participants could not be blinded to the access site (Appendix Figure 1) Table 1. Details of Studies Included in Meta analysis Table 2. Patients and Procedural Characteristics Appendix Figure 1. Risk of bias in the studies included in the meta analysis. Plus sign denotes low risk. Minus sign denotes high risk. MATRIX Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX; RIFLE STEACS Radial Versus Femoral Randomized Investigation in ST Elevation Acute Coronary Syndrome; RIVAL A Trial of Trans radial Versus Trans femoral Percutaneous Coronary Intervention Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy; STEMI RADIAL Trial Comparing Radial and Femoral Approach in Primary Percutaneous Coronary Intervention. The mean or median age of participants in the 4 trials ranged between 62 and 65 years, and men accounted for 72% to 79% of patients. In studies that reported sheath size, 6 French sheaths were used in most cases. Heparin, unfractionated or low molecular weight, was the most commonly used anticoagulant, and the use of glycoprotein IIb/IIIa inhibitors ranged widely across studies according to clinical presentation (Table 2) Procedural Duration and Access Site Crossover Data on procedural duration were available in RIFLE STEACS (17) STEMI RADIAL (18) and a substudy of RIVAL for a proportion of patients undergoing primary or rescue percutaneous coronary intervention (37) Overall, radial procedures lasted longer than femoral procedures, although the difference was trivial (standardized mean difference, 0.11 minutes [95% CI, 0.04 to 0.18 minutes] P= 0.002) Radial access was associated with a 4 fold higher risk for access site crossover (P< 0.001) (Appendix Figure 2) However, the pooled rates of access site crossover were low in both groups (6.3% in the radial group and 1.7% in the femoral group) Appendix Figure 2. Meta analysis of radial versus femoral access for access site crossover. MATRIX Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX; RIFLE STEACS Radial Versus Femoral Randomized Investigation in ST Elevation Acute Coronary Syndrome; RIVAL A T
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