The Lancet APRIL 23, 2011

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial

Sanjit S Jolly, Kari Niemelä, Denis Xavier, et al.

Bottom Line

In patients with acute coronary syndromes undergoing invasive management, radial artery access did not reduce the primary composite endpoint of death, myocardial infarction, stroke, or non-CABG-related major bleeding at 30 days compared to femoral access, though it significantly lowered rates of major vascular access site complications.

Key Findings

1. The primary composite outcome (death, myocardial infarction, stroke, or non-CABG major bleeding at 30 days) occurred in 3.7% of the radial access group versus 4.0% in the femoral access group (hazard ratio 0.92; 95% CI 0.72-1.17; p=0.50).
2. Major vascular access site complications were significantly reduced with radial access (1.4%) compared to femoral access (3.7%; p<0.0001).
3. Radial access was associated with a higher rate of access site crossover (7.6% vs 2.0%; p<0.0001).
4. Subgroup analysis indicated that high-volume radial PCI centers experienced a significant reduction in the primary outcome with radial access compared to femoral access (hazard ratio 0.49; 95% CI 0.28-0.87; p=0.021).

Study Design

Design
RCT
Open-Label
Sample
7,021
Patients
Duration
30 days
Median
Setting
Multicenter, 32 countries
Population Patients with acute coronary syndromes (both STEMI and NSTE-ACS) scheduled for coronary angiography and potential intervention
Intervention Radial artery access for coronary angiography/intervention
Comparator Femoral artery access for coronary angiography/intervention
Outcome Composite of death, myocardial infarction, stroke, or non-CABG-related major bleeding at 30 days

Study Limitations

The study was performed at experienced centers by operators with significant proficiency in both techniques, potentially underestimating the complication rates of less experienced operators.
The relatively low overall rate of major bleeding may have limited the trial's power to detect a statistically significant difference in bleeding outcomes between the groups.
Practice patterns regarding anticoagulation (e.g., low use of bivalirudin, high use of glycoprotein IIb/IIIa inhibitors) may influence the generalizability of the bleeding reduction findings to current practice.

Clinical Significance

The RIVAL trial established that radial artery access is a safe and effective alternative to the traditional femoral approach for patients with acute coronary syndromes, offering a clear advantage in reducing vascular access site complications without compromising procedural efficacy, particularly in high-volume settings.

Historical Context

Prior to RIVAL, the debate regarding radial versus femoral access was largely guided by observational studies and small randomized trials that suggested radial access might reduce bleeding. RIVAL was the first large-scale, international randomized controlled trial designed to definitively compare these strategies for primary clinical outcomes in an acute coronary syndrome population.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

Anatomically, why does the radial artery approach significantly reduce the risk of major vascular complications compared to the femoral approach, as demonstrated in the RIVAL trial?

Key Response

The radial artery is superficial, smaller in caliber, and sits directly over the distal radius (a bony structure), making it easily compressible in the event of bleeding. In contrast, the femoral artery is deeper, larger, and located near the retroperitoneal space; bleeding at this site can be occult and difficult to tamponade, leading to the higher rates of hematomas and pseudoaneurysms observed in the femoral arm of the study.

Resident
Resident

The RIVAL trial showed no significant difference in the primary composite endpoint for the total population but showed a benefit in the STEMI subgroup. How should this influence your choice of access site in a patient presenting with an inferior STEMI versus NSTE-ACS?

Key Response

While the overall trial was neutral, the pre-specified subgroup analysis for STEMI patients suggested a reduction in death, MI, or stroke. In STEMI, where patients are heavily anticoagulated and require urgent reperfusion, the bleeding benefit of radial access may translate into a mortality benefit (as later confirmed in trials like MATRIX). Therefore, radial access is preferred in STEMI when the operator is proficient, whereas in NSTE-ACS, the choice may be more flexible based on operator expertise.

Fellow
Fellow

The RIVAL trial demonstrated a significant interaction between center radial volume and the primary endpoint. What are the implications of this 'volume-outcome' relationship for the global generalizability of radial-first strategies?

Key Response

The trial found that benefit from radial access was primarily realized in high-volume radial centers (p=0.021 for interaction). This suggests that the 'radial advantage' is not intrinsic to the route alone but is highly dependent on operator proficiency. For a fellow, this emphasizes that the learning curve for radial access (estimated at 30-50 cases for basic proficiency) must be overcome before the theoretical benefits in safety and mortality can be clinically realized in high-risk ACS patients.

Attending
Attending

RIVAL failed to meet its primary composite endpoint of death, MI, stroke, or non-CABG bleeding, yet it is considered a landmark trial that catalyzed the shift to radial access. How do you reconcile a statistically neutral primary endpoint with a change in standard of care?

Key Response

The shift occurred because radial access demonstrated a clear, significant reduction in major vascular complications (1.4% vs 3.7%, p<0.0001) and was preferred by patients for earlier mobilization. In clinical practice, if two procedures offer similar hard outcomes (death/MI) but one significantly reduces procedural morbidity and improves patient experience, the safer profile dictates the standard of care, especially as subsequent meta-analyses and trials (MATRIX, RIVAL-STEMI) eventually showed mortality benefits in high-risk subsets.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

The RIVAL trial utilized a non-CABG-related major bleeding definition. How does the choice of bleeding scale (e.g., ACUITY, GUSTO, or TIMI) impact the sensitivity of a trial to detect differences between radial and femoral access, and why might this explain the neutral primary result?

Key Response

The primary endpoint in RIVAL used a composite that included bleeding, but different bleeding definitions vary in their inclusion of hematomas or access-site complications. RIVAL used a relatively strict 'major' bleeding definition. If a trial uses a more sensitive scale (like BARC or ACUITY) that captures smaller but clinically relevant access-site bleeds, the statistical power to find a difference increases. The neutral result in RIVAL's primary endpoint may partly stem from the dilution of the bleeding benefit by the harder endpoints of death and MI in a non-optimized (lower volume) population.

Journal Editor
Journal Editor

RIVAL reported a 7.6% crossover rate from the radial to the femoral group, compared to only 2.0% from femoral to radial. How does this high crossover rate affect the interpretation of the 'Intention-to-Treat' (ITT) analysis, particularly regarding the safety outcomes?

Key Response

In an ITT analysis, crossovers from radial to femoral are still analyzed in the radial group. Since these patients actually received the femoral procedure—often after a failed radial attempt—they are exposed to the higher risks of the femoral site. This 'dilutes' the perceived safety benefit of the radial approach. A reviewer would flag this as a potential bias toward the null, suggesting that the radial approach might actually be even safer than the ITT results indicate, although the Per-Protocol analysis usually helps clarify this.

Guideline Committee
Guideline Committee

How did the RIVAL trial's subgroup findings regarding STEMI and operator volume influence the evolution of the Class of Recommendation for radial access in subsequent ESC and ACC/AHA guidelines?

Key Response

RIVAL provided the first large-scale randomized evidence that radial access was non-inferior and safer regarding local complications. Based on RIVAL and subsequent trials like MATRIX, the ESC guidelines moved to a Class I (Level A) recommendation for radial access in ACS. The ACC/AHA guidelines also elevated radial access to Class I, specifically highlighting that the benefit is most pronounced in STEMI and when performed by 'radial-expert' operators, directly reflecting the RIVAL subgroup interactions.

Clinical Landscape

Noteworthy Related Trials

2008

RFAVI Trial

n = 702 · JACC

Tested

Radial artery access

Population

Patients undergoing PCI

Comparator

Femoral artery access

Endpoint

Vascular complications

Key result: Radial access was associated with a significant reduction in vascular complications compared to femoral access.
2015

MATRIX Trial

n = 8,404 · Lancet

Tested

Radial access

Population

Patients with acute coronary syndromes undergoing invasive management

Comparator

Femoral access

Endpoint

Major adverse cardiovascular events (MACE) and net adverse clinical events (NACE)

Key result: Radial access significantly reduced the rate of NACE and all-cause mortality compared to femoral access in patients with ACS.
2017

SAFARI-STEMI Trial

n = 2,292 · JACC

Tested

Radial access

Population

Patients with ST-segment elevation myocardial infarction

Comparator

Femoral access

Endpoint

All-cause mortality, MI, or stroke at 30 days

Key result: The radial approach did not show a statistically significant difference in the primary composite endpoint compared to femoral access in STEMI patients.

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