Author + information
- Received June 18, 2013
- Revision received September 29, 2013
- Accepted October 8, 2013
- Published online March 18, 2014.
- Sanjit S. Jolly, MD, MSc∗∗ (, )
- John Cairns, MD†,
- Salim Yusuf, MBBS, DPhil∗,
- Kari Niemela, MD, PhD‡,
- Philippe Gabriel Steg, MD§,
- Matthew Worthley, MD‖,
- Emile Ferrari, MD¶,
- Warren J. Cantor, MD#,
- Anthony Fung, MD†,
- Nicholas Valettas, MD, MSc∗,
- Michael Rokoss, MD∗,
- Goran K. Olivecrona, MD, PhD∗∗,
- Petr Widimsky, MD††,
- Asim N. Cheema, MD, PhD‡‡,
- Peggy Gao, MSc∗,
- Shamir R. Mehta, MD, MSc∗,
- RIVAL Investigators
- ∗McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
- †University of British Columbia, Vancouver, British Columbia, Canada
- ‡Tampere University Hospital and Heart Center, Tampere, Finland
- §Université Paris-Diderot, Paris, France
- ‖University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia
- ¶Hopital Pasteur, Nice, France
- #Southlake Regional Health Centre, University of Toronto, Ontario, Canada
- ∗∗Skane University Hospital, Lund, Sweden
- ††Charles University, Hospital Kralovske Vinohrady, Prague, Czech Republic
- ‡‡St. Michael's Hospital, University of Toronto, Ontario, Canada
- ↵∗Reprint requests and correspondence:
Dr. Sanjit S. Jolly, Room C3 118 CVSRI Building, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Objectives The study sought to evaluate the relationship between procedural volume and outcomes with radial and femoral approach.
Background RIVAL (RadIal Vs. femorAL) was a randomized trial of radial versus femoral access for coronary angiography/intervention (N = 7,021), which overall did not show a difference in primary outcome of death, myocardial infarction, stroke, or non–coronary artery bypass graft major bleeding.
Methods In pre-specified subgroup analyses, the hazard ratios for the primary outcome were compared among centers divided by tertiles and among individual operators. A multivariable Cox proportional hazards model was used to determine the independent effect of center and operator volumes after adjusting for other variables.
Results In high-volume radial centers, the primary outcome was reduced with radial versus femoral access (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.87) but not in intermediate- (HR: 1.23; 95% CI: 0.88 to 1.72) or low-volume centers (HR: 0.83; 95% CI: 0.52 to 1.31; interaction p = 0.021). High-volume centers enrolled a higher proportion of ST-segment elevation myocardial infarction (STEMI). After adjustment for STEMI, the benefit of radial access persisted at high-volume radial centers. There was no difference in the primary outcome between radial and femoral access by operator volume: high-volume operators (HR: 0.79; 95% CI: 0.48 to 1.28), intermediate (HR: 0.87; 95% CI: 0.60 to 1.27), and low (HR: 1.10; 95% CI: 0.74 to 1.65; interaction p = 0.536). However, in a multivariable model, overall center volume and radial center volume were independently associated with the primary outcome but not femoral center volume (overall percutaneous coronary intervention volume HR: 0.92, 95% CI: 0.88 to 0.96; radial volume HR: 0.88, 95% CI: 0.80 to 0.97; and femoral volume HR: 1.00, 95% CI: 0.94 to 1.07; p = 0.98).
Conclusions Procedural volume and expertise are important, particularly for radial percutaneous coronary intervention. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention [PCI] Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273)
- acute coronary syndrome(s)
- femoral access
- percutaneous coronary intervention
- procedural volume
- radial access
Unlike a new drug therapy, a procedural or surgical innovation is likely dependent on the skill and experience of the physicians performing the technique. Accordingly, the Consolidated Standards of Reporting Trials (CONSORT) guidelines recommend that all randomized trials of nonpharmacological interventions collect data and perform analyses based on procedural volume (1).
Greater percutaneous coronary intervention (PCI) procedural volume has been linked to improved clinical outcomes in studies reporting primarily femoral access (2,3). These data have led to the American College of Cardiology, American Heart Association, and Society of Cardiac Angiography and Intervention guidelines recommending a minimum of 75 PCI procedures per year for an interventional cardiologist to enhance patient safety (4). However, radial access is technically more challenging and may have a longer learning curve and require higher volumes to achieve and maintain proficiency (5). With rapidly increasing use of radial access, it is important to understand the relationship between procedural volume and outcomes with this technique.
The RIVAL (RadIal Vs. femorAL) trial randomized 7,021 patients with acute coronary syndromes (ACS) to radial versus femoral access for coronary angiography and intervention (6,7). The trial showed no difference between radial and femoral access for the primary outcome of death, myocardial infarction (MI), stroke, or non–coronary artery bypass graft surgery (CABG)–related major bleeding, but radial access was associated with a statistically significant 63% reduction in major vascular complications. In the subgroup of high-volume radial centers the primary outcome was reduced by radial versus femoral access, but it was not reduced in intermediate- or low-volume radial centers. There was no significant interaction by individual operator radial volume.
The objective of the present analyses is to explore in greater depth the interaction between procedural volumes and access site for various outcomes in the RIVAL trial.
The design of the RIVAL trial has been previously published (6). It was a prospective randomized trial among patients with acute coronary syndromes comparing radial versus femoral access for coronary angiography and same sitting PCI if clinically indicated. Between June 6, 2006, and November 3, 2010, 7,021 patients were enrolled from 158 hospitals in 32 countries.
Patients were eligible for the study if: 1) they presented with non–ST-segment or ST-segment elevation ACS; 2) they were to be managed with an invasive approach; 3) the interventional cardiologist was willing to proceed with either radial or femoral approach (and had expertise with both, including at least 50 radial procedures within the previous year); and 4) the patient had intact dual circulation of the hand documented by Allen's test. Patients were not eligible if they presented with cardiogenic shock, had severe peripheral vascular disease precluding a femoral approach, or had prior coronary bypass surgery with use of more than 1 internal mammary artery.
The primary outcome was the composite of death, MI, stroke, or non–CABG-related major bleeding. Each center was required to report the number of overall, radial, and femoral procedures per year for participating operators. At each center, the median operator volume for a center was calculated and used to classify center volume because overall center volume was not collected.
Centers were divided into tertiles according to the median radial PCI volume of their operators: (low [≤60 radial PCI/year/operator], intermediate [61 to 146 radial PCI/year/operator], and high [>146 radial PCI/year/operator]). The tertile analysis for center and operator volume was pre-specified.
Baseline characteristics and cointerventions were documented for the tertiles of low-, intermediate-, and high-volume radial centers (Table 1). The hazard ratios of radial versus femoral access for the primary outcome and secondary outcomes were compared within these tertiles.
ST-segment elevation MI and center volume
High-volume radial centers enrolled significantly higher proportion of ST-segment elevation myocardial infarction (STEMI). Interactions were observed with benefit of radial access in both STEMI subgroup and high-volume radial centers. As a result, an adjusted analysis was performed using the diagnosis of STEMI prior to randomization in a Cox proportional hazards model to help determine the independent effect of volume apart from STEMI (8).
For operator-level data instead of center-level analyses, operators were divided into tertiles according to individual operator radial PCI volume: (low [≤70 radial PCI/year/operator], intermediate [71 to 142 radial PCI/year/operator], high [>142 radial PCI/year/operator]). The hazard ratios (HRs) for the primary and secondary outcomes were compared within these tertiles. Finally, for both center and operator tertiles, stratified analyses for STEMI and non–ST-segment elevation acute coronary syndromes (NSTEACS) were performed.
All analyses were by intention to treat, unless otherwise specified. For subgroup analyses, HRs and 95% confidence intervals (CIs) and interaction p values were calculated. Statistical interactions were evaluated at a significance level of 0.05 with no adjustment made for multiple comparisons.
Observational multivariable analyses of volume and outcome
A multivariable analysis with a Cox proportional hazards model was performed to determine if overall (radial and femoral) center PCI volume (per 50 PCI/year for center's median operator volume) was independently associated with the primary outcome, mortality, and non-CABG major bleeding after adjusting for age, sex, diabetes, prior PCI, creatinine, systolic blood pressure and heart rate at presentation, STEMI, elevated biomarker at presentation, Killip class, in-hospital PCI, in-hospital coronary bypass surgery, glycoprotein IIb/IIIa inhibitor therapy, and enrollment during the CURRENT (Clopidogrel and Aspirin Optimal Usage to Reduce Recurrent evenTs) trial or after.
A similar analysis was repeated for radial PCI center volumes for patients randomized to radial access and femoral PCI center volumes for patients randomized to femoral access. Finally, this analysis was repeated at the individual operator level for overall operator PCI volume, radial volume, and femoral volume. The same variables for operator-level analysis were used as for center analysis in the Cox proportional hazards model.
All statistical analyses were performed using SAS version 9.1 (SAS Institute Inc., Cary, North Carolina).
The baseline characteristics of patients enrolled from low-, intermediate-, and high-volume radial centers are shown in Table 1. High-volume centers were more likely to enroll STEMI patients and patients with Killip class ≥2 heart failure at presentation. High-volume radial centers had higher PCI rates, perhaps explained by their higher proportion of subjects with STEMI. Intermediate-volume radial centers randomized a higher proportion of elderly patients (age >75 years) with biomarker-positive NSTEACS. Lower-volume radial centers tended to use more diagnostic catheters and were more likely to use 3 or more PCI guide catheters during a procedure.
Among patients undergoing primary PCI, door-to-balloon times were not collected, but the time from randomization to completion of PCI was longer in radial than femoral procedures in low- (65 min vs. 52 min; p < 0.001) and intermediate-volume centers (72 min vs. 60 min; p = 0.011), but was not significantly different in high-volume radial centers (55 min vs. 51 min; p = 0.78) (Fig. 1). Low-volume radial centers performed 20% of PCI procedures per year via radial access, whereas high-volume centers performed 75% (Table 2).
Radial versus femoral access in subgroups of center volume (low, intermediate, and high)
For the primary outcome, a benefit was observed for radial versus femoral access in the highest-volume radial centers (1.6% vs. 3.2%; HR: 0.49, 95% CI: 0.28 to 0.87) but not in intermediate- (5.4% vs. 4.4%; HR: 1.23, 95% CI: 0.88 to 1.72) or low-volume radial centers (3.4% vs. 4.2%; HR: 0.83, 95% CI: 0.52 to 1.31; interaction p = 0.021) (Table 3).
For the composite of death, MI, or stroke, a benefit was observed for radial versus femoral access in the highest-volume radial centers (1.3% vs. 2.7%; HR: 0.50, 95% CI: 0.27 to 0.92) but not in intermediate- (4.9% vs. 3.6%; HR: 1.38, 95% CI: 0.96 to 1.98) or low-volume radial centers (2.8% vs. 3.4%; HR: 0.82, 95% CI: 0.49 to 1.36; interaction p = 0.013) (Table 3).
Among the subgroups of high-, intermediate-, and low-volume radial centers, there were no differences in the outcome of non-CABG major bleeding using the RIVAL definition for radial versus femoral access (Table 3). However, for ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial non-CABG major bleeding, the largest reductions with radial access occurred at high-volume radial centers (HR: 0.23, 95% CI: 0.12 to 0.43) compared with intermediate- (HR: 0.59, 95% CI: 0.40 to 0.87) and low-volume radial centers (HR: 0.41, 95% CI: 0.21 to 0.77; interaction p = 0.037). The lowest access site crossover from radial to femoral was observed in highest-volume radial centers (HR: 1.92, 95% CI: 1.19 to 3.08) compared with intermediate- (HR: 4.22, 95% CI: 2.89 to 6.18) and low-volume radial centers (HR: 7.13, 95% CI: 3.79 to 13.40; interaction p = 0.003).
There were no differences in PCI success rates or angiographic complications between radial and femoral access across the subgroups of high, intermediate, and low radial center volume (Table 3).
Femoral outcomes in different radial tertiles
To determine if the benefit of radial access in high-volume radial centers was due to poorer outcomes in femoral patients, we performed an adjusted analysis comparing patients randomized to femoral access between low- and high-volume radial sites using variables listed in the Methods section. There were no significant differences for primary outcome for patients randomized to femoral access (high-volume radial centers 3.2% vs. low-volume 4.2% for femoral patients; adjusted HR: 0.67, 95% CI: 0.42 to 1.09; p = 0.10) and non-CABG major bleeding (adjusted HR: 1.07, 95% CI: 0.41 to 2.79; p = 0.89).
Radial versus femoral access in subgroups of individual operator volume (low, intermediate, and high)
For the primary outcome, there were no significant differences between radial and femoral access in the tertiles of high- (2.5% vs. 3.1%; HR: 0.79, 95% CI: 0.48 to 1.29), intermediate- (4.3% vs. 4.9%; HR: 0.87, 95% CI: 0.60 to 1.27), and low-volume radial operators (4.2% vs. 3.8%; HR: 1.10, 95% CI: 0.74 to 1.65; interaction p = 0.54). There were no significant differences in the components of the primary outcome between radial versus femoral access in the subgroups of high-, intermediate-, and low-volume radial operators (Table 4). There were significant reductions in major vascular complications with radial versus femoral access within each of the tertiles of high-, intermediate-, and low-volume radial operators (Table 4).
Benefit of radial in high-volume centers persists after adjustment for STEMI
High-volume centers enrolled a much higher proportion of STEMI, and given the interaction of both the STEMI and center subgroups, it was important to determine the independent effect of volume after accounting for STEMI. After adjusting for STEMI in the Cox proportional hazards model, the benefit of radial versus femoral access persisted in high-volume radial centers (adjusted HR: 0.50, 95% CI: 0.28 to 0.88) compared with the intermediate- (HR: 1.24, 95% CI: 0.89 to 1.73) and low-volume radial centers (adjusted HR: 0.83, 95% CI: 0.52 to 1.31; interaction p = 0.020). The results for center and operator tertiles stratified by STEMI versus NSTEACS are shown in Table 5 and show consistent findings for the primary outcome.
PCI center volume and outcome (multivariable observational analysis)
In a multivariable analysis, increasing PCI center volume (per 50 PCI for median operator at center) was independently associated with improved rates of primary outcome (adjusted HR: 0.92, 95% CI: 0.88 to 0.96) (Fig. 2, Online Table 1). Other independent predictors of the primary outcome were age, serum creatinine level, systolic blood pressure at presentation, STEMI at presentation, Killip class II heart failure, and prior CABG surgery.
Similarly, in a multivariable analysis in only radial patients, radial PCI center volume was also independently associated with improved rates of primary outcome (adjusted HR: 0.88, 95% CI: 0.80 to 0.97) (Fig. 2, Online Table 2). Finally, in a multivariable analysis in only femoral patients, femoral PCI center volume (adjusted HR: 1.00, 95% CI: 0.94 to 1.07) was not independently associated with primary outcome (Fig. 2, Online Table 3).
For mortality, overall PCI center volume (HR: 0.94, 95% CI: 0.88 to 1.01), radial volume (HR: 0.90, 95% CI: 0.77 to 1.04), or femoral volume (HR: 1.03, 95% CI: 0.92 to 1.14) were not independently associated with overall mortality (Fig. 2). For non-CABG major bleeding, overall PCI center volume was independently associated with lower rates of non-CABG major bleeding (HR: 0.82, 95% CI: 0.73 to 0.92), but this was not significant for radial center volume (HR: 0.84, 95% CI: 0.64 to 1.10) or femoral center volume (HR: 0.94, 95% CI: 0.81 to 1.09).
Individual PCI operator volume and outcome (multivariable analysis)
In a multivariable analysis, using individual PCI operator volume as a continuous variable, increasing overall PCI (radial + femoral) operator volume (per 50 PCI) was independently associated with improved rates of the primary outcome (adjusted HR: 0.94, 95% CI: 0.90 to 0.97) (Fig. 3). Similarly, in a multivariable analysis in only radial patients, radial operator volume was also independently associated with primary outcome (adjusted HR: 0.90, 95% CI: 0.83 to 0.98) (Fig. 3). In femoral patients, femoral operator volume (adjusted HR: 1.00, 95% CI: 0.94 to 1.07) was not independently associated with primary outcome (Fig. 3).
RIVAL is the largest trial to compare radial versus femoral access among patients with acute coronary syndromes. In high-volume radial centers, radial access significantly reduced the primary outcome compared with femoral access, but this was not observed in intermediate- or low-volume radial centers. By contrast, we found no interaction according to individual operator radial volume. At the level of both center and operator, overall PCI volume and radial volume were independently associated with the primary outcome, but not femoral volume.
Prior PCI data from administrative databases have shown center volume to be a more robust predictor of outcome compared to individual operator volume (2,8). The stronger relationship with center volume and outcome in the literature may provide insight into our findings of a significant subgroup interaction at the center level but not operator level for radial access (7). In an analysis of the New York Registry (N = 107,713), after adjustment for case mix, mortality after PCI was only associated with center volume and not operator volume (8). Similarly, in an analysis from the Medicare National Claims Database (N = 167,208), after adjustment, mortality was only associated with center volume and not operator volume (2). It is possible that the center effect is greater due to the care of the whole team of healthcare providers (interventional fellows and nurses) and center resources rather than just the individual senior physician.
Finally, is it possible the benefit observed in high-volume radial centers is due to their lack of expertise with femoral access and worse femoral outcomes? This hypothesis is not supported by the data in the RIVAL trial; the primary outcome rates trended lower among femoral cases in high-volume radial centers compared with low-volume radial centers, which were primarily femoral centers (3.8% vs. 4.2%, respectively) with similar rates of non-CABG major bleeding.
Prior studies in predominantly femoral PCI have demonstrated improved outcomes in operators performing more than 50 PCI procedures per year (2). The lack of a relationship between femoral PCI volume and outcome in the RIVAL study may be due to the fact that the procedural volume range in RIVAL was much higher than most prior studies (median PCI volume of 300/year/operator; interquartile range: 190 to 400) so that the level of experience for femoral procedures was high enough in all centers, such that they were all similarly expert.
First, lifetime experience of radial access of operators at our centers was not captured in the RIVAL study. It is possible that senior individuals performing radial access for many years may have a different annual volume outcome relationship than individuals with less experience. Second, the involvement of trainees during procedures was not recorded and it is possible that larger, higher-volume centers may have more trainees involved in procedures. Third, subgroup findings should generally be considered exploratory despite being pre-specified and consistent with pre-specified direction. Fourth, procedural volume may be an imperfect surrogate for expertise as some operators may require different annual volume to achieve the same proficiency. Fifth, lifetime procedural volume was not collected in RIVAL so we cannot identify a minimum of procedures for proficiency. Finally, the association between procedural volume and outcome may not be causal as there may be other variables that impact outcomes at these institutions.
In the RIVAL trial, radial access compared with femoral access reduced the primary outcome in high-volume radial centers. Increasing procedural volume was independently associated with better outcomes particularly with radial access.
The Population Health Research Institute has received research support from sanofi-aventis, Bristol-Myers Squibb, and Medtronic. Dr. Jolly has received consulting fees (modest) from sanofi-aventis, GlaxoSmithKline, and AstraZeneca. Dr. Cairns has recently chaired or been a member of the data and safety monitoring board of the following industry-sponsored trials: PALLAS (sanofi-aventis), ACTIVE (sanofi-aventis), and AVERROES (Bristol-Myers Squibb); has served as a consultant to Boehringer Ingelheim Canada; and is a member of the steering committee of the TOTAL trial, which receives funding from Medtronic. Dr. Steg has received research support from sanofi-aventis and Servier; has served as a consultant and received honoraria (modest) from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo-Lilly, GlaxoSmithKline, Merck, Otsuka, Roche, sanofi-aventis, Servier, and The Medicines Company; and owns stock options in Aterovax. Dr. Mehta has received consulting fees/honoraria (modest) from Abbott Vascular, sanofi-aventis, Eli Lilly, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- acute coronary syndrome(s)
- coronary artery bypass graft
- confidence interval
- hazard ratio
- myocardial infarction
- non–ST-segment elevation acute coronary syndromes
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- Received June 18, 2013.
- Revision received September 29, 2013.
- Accepted October 8, 2013.
- American College of Cardiology Foundation
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