Original Contribution

Radial Versus Femoral Approach in Women Undergoing Coronary Angiography: A Meta-Analysis of Randomized Controlled Trials

Shadi Al Halabi, MD, MPH1;  Lucas Burke, MD1;  Fizza Hussain, MD2;  John Lopez, MD1;  Verghese Mathew, MD1;  Ivo Bernat, MD, PhD3;  Adhir Shroff, MD, MPH4

Shadi Al Halabi, MD, MPH1;  Lucas Burke, MD1;  Fizza Hussain, MD2;  John Lopez, MD1;  Verghese Mathew, MD1;  Ivo Bernat, MD, PhD3;  Adhir Shroff, MD, MPH4

Abstract: Objectives. We sought to compare outcomes with radial vs femoral approach in female patients undergoing coronary angiography. Background. Women undergoing cardiac procedures have increased risk of bleeding and vascular complications, but are under-represented in randomized clinical trials (RCTs) involving coronary angiography. Methods. We performed a meta-analysis of RCTs comparing outcomes in women undergoing angiography with radial vs femoral approaches. The primary outcome was non-coronary artery bypass graft (CABG) related bleeding at 30 days. Secondary outcomes included major adverse cardiovascular or cerebrovascular events (MACCE; a composite of death, stroke or myocardial infarction), vascular complications, procedure duration, and access-site crossover. Results. Four studies (n = 6041 female patients) met the inclusion criteria. In female patients undergoing coronary angiography, radial access decreased non-CABG related bleeding (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.44-0.72; P<.001), MACCE (OR, 0.73; 95% CI, 0.58-0.93; P=.01), vascular complications (OR, 0.49; 95% CI, 0.32-0.75; P<.001) with no significant difference in procedure time (mean difference, 0.04; 95% CI, -0.97 to 0.89; P=.93). There was an increase in access-site crossover using the radial approach (OR, 2.86; 95% CI, 2.24-3.63; P<.001). Patients undergoing radial approach were more likely to prefer radial access for the next procedure (OR, 6.96; 95% CI, 5.70-8.50; P<.001). Conclusions. In female patients undergoing coronary angiography or intervention, the radial approach is associated with decreased bleeding, MACCE, and vascular complications. These data suggest that radial access should be the preferred approach for women.

J INVASIVE CARDIOL 2019 August 15 (Epub Ahead of Print).

Key words: bleeding, coronary angiography, female, femoral, mortality, percutaneous coronary intervention, radial, vascular complications, women

Women are at particularly higher risk of bleeding and vascular complications after percutaneous coronary intervention (PCI), and such complications are strongly associated with worse clinical outcomes in patients with acute coronary syndrome (ACS).1-4 The radial artery approach is a proven strategy to reduce bleeding risk in patients undergoing PCI; however, not all randomized trials have consistently shown a benefit of radial access in women.5 Observational data also suggest that women are much less likely to undergo radial access than men.6 This may be related to the smaller-caliber radial artery and its propensity to spasm. It is essential therefore to address the risk of bleeding in women undergoing coronary angiography, especially since women are under-represented in the medical literature.

The aim of this study was therefore to determine whether radial artery access was superior to femoral artery access in women undergoing coronary angiography or intervention with respect to bleeding, major adverse cardiovascular and cerebrovascular event (MACCE) rate, and vascular complications.


This meta-analysis was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).7

Literature review. We searched five databases (Pubmed, Medline, Embase, Ovid, and Cochrane) for relevant studies from January 1980 to June 2018. We searched prior systemic reviews to ensure inclusion of all eligible studies. We searched ClinicalTrials.gov to identify any ongoing randomized controlled trials (RCTs). This search was independently conducted by two investigators (SA and LB). Key terms included radial access, femoral access, angiography, percutaneous intervention, ischemic heart disease, acute coronary syndrome, women, female, mortality, bleeding, vascular complications, crossover, and fluoroscopy time.

Selection criteria and quality analysis. We used the following inclusion criteria: (1) prospective RCT that included at least 500 patients; (2) study patients underwent angiography and/or percutaneous intervention; (3) study compared radial with femoral access; (4) study included women; and (5) study reported at least one of the studied outcomes. Studies where outcomes for women were not available and those only published in abstract form were excluded. The quality of each RCT was assessed using Jadad’s scale.8

Data extraction. Relevant information was collected independently by three investigators (SA/LB/FH). These data included age, comorbidities, type of procedure, mortality, vascular complications, bleeding complications, fluoroscopy time, and patient preferences. Discrepancies were discussed and resolved by consensus.

Outcomes. The primary outcome was non-coronary artery bypass graft (CABG) related bleeding, which included the Bleeding Academic Research Consortium (BARC) definitions 2, 3, and 5. We performed multiple secondary analyses, including MACCE at 30 days, vascular complications, fluoroscopy time, and patient preference. Vascular complications included pseudoaneurysms requiring ultrasound compression, closure, or thrombin injection, arteriovenous fistulas, arteriovenous fistulas requiring intervention, limb ischemia, arterial occlusion requiring intervention, periprocedural access-site bleeding requiring anticoagulation reversal, large hematoma requiring prolonged hospitalization, damage to an adjacent nerve, and access-site complications requiring surgical or percutaneous intervention.

Statistical analysis. Fixed-effect models were used for all reported outcomes. Additional analysis was conducted using the random-effect model. We reported the effect measure for each outcome as the odds ratio (OR) with the related 95% confidence interval (CI).

Heterogeneity among studies was assessed with the inconsistency index (I2) statistic, which ranges from 0% to 100% and is defined as the percentage of the observed inter-trial variability that is due to heterogeneity rather than chance for each outcome (I2 >75% denotes significant heterogeneity). Potential publication bias was evaluated by means of Begg’s funnel-plot method.9 Two-tailed probability values of <.05 were considered significant. RevMan version 5.3 (The Cochrane Collaboration) was used for all analyses.


Study selection. Of 168 papers originally retrieved by searching the databases, four met the inclusion criteria. The selection process is detailed in Figure 1.

Characteristics of included studies and patients. The four RCTs were published between 2011 and 2018 and involved 6041 patients.5,10-12 One study was conducted in the United States, two were conducted in Europe, and one was multinational. All trials were published in English.

Most patients received acetylsalicylic acid (ASA) prior to PCI in two trials.11,12 One trial noted a high proportion of in-hospital ASA use,10 while all patients were recommended to receive aspirin in another trial.5 A high proportion of patients received a thienopyridine in two trials.11,12 One trial noted a high proportion of in-hospital thienopyridine use,10 while thienopyridine was recommended for all patients in another trial.5 The use of bivalirudin, heparin, and low molecular weight heparin varied between all four trials, as did the use of glycoprotein IIb/IIIa inhibitors.5,10-12 The mean age of patients included in the trials ranged from 54 to 82 years. Three trials included patients with ACS only, whereas one trial was made up of both ACS and non-ACS patients.5 The majority of patients underwent PCI in three trials,10-12 while a minority of patients underwent PCI in one trial.5 Further patient and procedure characteristics are listed in Table 1.

All of the trials were of high quality (≥3/5) according to the Jadad quality assessment score. There was no blinding, as this would not be possible for either the interventionalist or patient when comparing radial vs femoral artery access. All crossovers were accounted for in the four studies,10-12 and the reasons for crossover were reported in three of the studies.5,10-12

We were able to obtain unpublished outcomes specifically for women from one of the trials that met the inclusion criteria.12

Effects of radial vs femoral access on bleeding. For the endpoint of bleeding, all four studies reported non-CABG related bleeding events.5,10-12 Major bleeding occurred in 103 patients in the radial artery group and 188 patients in the femoral artery group. Radial artery access was associated with a significant reduction in major bleeding (OR, 0.56; 95% CI, 0.44-0.72; P<.001) (Figure 2).

Effects of radial vs femoral access on MACCE. Three studies reported death, stroke, or myocardial infarction at 30 days and radial access was associated with decreased MACCE.10-12 There were 129 MACCEs in the radial group compared with 183 events in the femoral group (OR, 0.73; 95% CI, 0.58-0.93; P=.01) (Figure 3).

Vascular complications. With regard to vascular complications, all four studies reported vascular complications.5,10-12 Vascular complications occurred in 33 patients in the radial artery group and 68 patients in the femoral artery group. Radial artery access was associated with a significant reduction in vascular complications when compared with femoral artery access (OR, 0.49; 95% CI, 0.32-0.75; P<.001) (Figure 4).

Access-site crossover. The rate of access-site crossover was reported in all four studies.5,10-12 The overall rate of access-site crossover was significantly higher in the radial access group, with 248 patients requiring a different access site as compared with 96 patients in the femoral artery group (OR, 2.86; 95% CI, 2.24-3.63; P<.001) (Figure 5). The predominant reason for crossover was radial artery spasm.5,10-12

Procedural time. Procedural time was reported for all four studies,5,10-12 and there was no significant difference between groups (mean difference, -0.04; 95% CI, -0.97 to 0.89; P=.97) (Figure 6).

Patient preference. Only two studies reported patient preference,5,10 but patients undergoing radial approach were more likely to prefer radial access for the next procedure (OR, 6.96; 95% CI, 5.70-8.50; P<.001).

Sensitivity analysis. We performed a sensitivity analysis, excluding one trial where <50% percent of patients underwent PCI and included the highest percentage of non-ACS patients.5 This analysis found that a radial approach continued to have a favorable effect on bleeding (OR, 0.58; 95% CI, 0.45-0.75; P<.001) and vascular complications (OR, 0.58; 95% CI, 0.39-0.87; P<.01). Another sensitivity analysis was performed using random-effects models with odds ratios as the effect measure, and yielded similar results.


This meta-analysis demonstrates that in female patients undergoing coronary angiography or PCI, radial artery access reduced major bleeding, MACCE, and vascular complications. There was no difference in procedural or fluoroscopic times, but higher rates of access-site crossover were associated with a radial approach. Finally, radial access was the preferred access site by patients when compared with femoral artery access.

The effects of using radial artery access for coronary angiography with regard to reducing the risk of bleeding in women was seen across all four studies. Large registries also demonstrate an association between female sex and higher bleeding rates associated with coronary angiography and PCI,13-15 which highlights the need for promoting this approach in real-world practice based on the results of the studies evaluated here.

This meta-analysis showed a significant decrease in MACCE. Recently, a large registry-based study from the United Kingdom that included 43,000 women undergoing PCI using the radial artery showed an association between radial access and a reduction in 30-day mortality and major adverse cardiovascular event (MACE) rates across a spectrum of clinical presentations.16 As such, the results of this meta-analysis of RCTs corroborates the credence that radial artery access may significantly improve outcomes in women undergoing coronary angiography and PCI.

Patient preference and shared decision-making with regard to choice of access site are important to consider when discussing catheter-based procedures with patients and their families.17 We found that patients undergoing catheterization via the radial artery were much more likely to prefer radial access for their next procedure. This is consistent with data from the recent PREVAS study by Kok et al,18 where 71.1% of patients with experience of both radial and femoral artery access for catheterization preferred use of the radial artery.

Despite sluggish adoption of radial artery access in the United States, the trend now demonstrates an almost linear relationship over time with regard to operators using the radial artery as the upfront site for performing PCI.19 Challenges with adopting radial artery access in women include smaller-caliber arteries, higher risk of radial artery spasm, and potential failure of PCI.20,21 We found a higher rate of crossover in the radial access arm, which was driven primarily by radial artery spasm.5,10-12 However, the improved outcomes with the radial artery approach likely warrant accepting a higher crossover rate after discussing the risks and benefits with the patient. In fact, the notion of incentivizing transradial access in primary PCI has been recently proposed by leaders in the field as a way of promoting this access-site approach.22

An important consideration of the trials evaluated in this meta-analysis involves the high proportion of ACS patients — a group that has been shown to have more frequent non-access site bleeding events when compared with non-ACS patients.23 While access-site bleeding rates have declined dramatically over time,24 non-access site bleeding events have not declined in a similar fashion in patients with ACS undergoing PCI.25 Thus, use of the radial artery for vascular access would not be expected to impact non-access site bleeding, which is associated with higher mortality at 1 year when compared with access-site bleeding events.25

Study limitations. First, we assessed outcomes only up to 30 days based on the reported outcomes in the included trials. Hence, we are unable to assess the long-term effects of each approach. Second, there was some variation in the definitions of bleeding and vascular complications used in the studies. Third, women are significantly under-represented in the majority of the radial vs femoral trials, and data on women are only seldom available. Thus, we sought data only from RCTs with >500 patients. Fourth, we are unable to comment on outcomes in women undergoing PCI only due to insufficient data from these trials.


Radial access has been shown to reduce mortality, access-site bleeding, and vascular complications.26 Women are also known to have higher bleeding risk than men.1-4,27 Although women potentially benefit from radial access due to higher baseline risk, observational large registries suggest they are less likely to undergo radial access.6,17 Additionally, landmark trials comparing radial and femoral access included mostly men. The results of this meta-analysis of the currently available RCTs comparing clinical outcomes between radial artery and femoral artery access for coronary angiography and PCI in women demonstrated that women benefit from a radial-first approach, and that this approach results in no significant difference in procedure time.


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From the 1Division of Cardiology and 2Department of Internal Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois; 3Department of Cardiology, University Hospital Pilsen, Pilsen, Czech Republic; and 4Division of Cardiology, University of Illinois, Chicago, Illinois.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bernat reports consulting/lecture income from Terumo. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted on March 6, 2019 and accepted on April 29, 2019.

Address for correspondence: Adhir Shroff, MD, MPH, Division of Cardiology, Department of Medicine University of Illinois Hospital & Health Sciences System, 740 West Taylor Street, Chicago, Il 60612. Email: arshroff@uic.edu