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, Salim Yusuf, John Cairns, et al.

Bottom Line

In patients with acute coronary syndromes, radial access was comparable to femoral access for the primary composite endpoint but significantly reduced major vascular access site complications and showed potential mortality/ischemic benefits in high-volume centers and STEMI patients.

Key Findings

1. The primary composite outcome of death, myocardial infarction (MI), stroke, or non-CABG-related major bleeding at 30 days occurred in 3.7% of the radial group and 4.0% of the femoral group (HR 0.92, 95% CI 0.72-1.17; p=0.50) [1.2.5].

2. Rates of non-CABG-related major bleeding alone were low and not significantly different between the two access routes (0.7% radial vs. 0.9% femoral; HR 0.73, p=0.23).

3. Major vascular access site complications were significantly reduced with radial access compared to femoral access (1.4% vs. 3.7%; p<0.0001), primarily driven by fewer large hematomas (1.2% vs. 3.0%; p<0.0001) and pseudoaneurysms requiring closure (0.2% vs. 0.6%; p=0.006).

4. In prespecified subgroup analyses, radial access significantly reduced the primary composite outcome in centers with the highest tertile of radial procedural volume (HR 0.49; p=0.015) and in patients presenting with ST-segment elevation myocardial infarction (STEMI) (HR 0.60; p=0.026).

Study Design

Design

RCT

Open-Label

Sample

7,021

Patients

Duration

30 days

Median

Setting

Multicenter, 32 countries

Population Patients with acute coronary syndromes (unstable angina, NSTEMI, or STEMI) undergoing coronary angiography with intent for possible percutaneous coronary intervention.

Intervention Radial artery access for coronary angiography and percutaneous coronary intervention.

Comparator Femoral artery access for coronary angiography and percutaneous coronary intervention.

Outcome A composite of death, myocardial infarction, stroke, or non-CABG-related major bleeding at 30 days.

Study Limitations

• The trial was open-label, meaning operators were not blinded to the access site, although clinical outcomes were assessed by a blinded committee.

• The study failed to meet its primary efficacy endpoint in the overall cohort; the significant benefits observed in high-volume centers and STEMI patients were derived from subgroup analyses.

• Participating operators were required to have performed at least 50 radial procedures in the preceding year; thus, the safety and efficacy outcomes may not be generalizable to low-volume or inexperienced radial operators.

Clinical Significance

The RIVAL trial was a landmark study that proved radial access is as effective as femoral access while dramatically reducing vascular access site complications in ACS patients. By demonstrating that high-radial-volume centers and STEMI patients derive substantial clinical benefits from the radial approach, the trial established the 'volume-outcome' relationship for radial access and catalyzed a major paradigm shift toward the 'radial first' strategy that now dominates international PCI guidelines.

Historical Context

Historically, the transfemoral approach was the standard access route for coronary angiography and intervention, despite being associated with bleeding and vascular complications that correlate with increased mortality in ACS patients. Prior to 2011, small randomized trials and observational registries suggested transradial access could lower bleeding rates. RIVAL was the first large-scale, multicenter, randomized trial designed to definitively compare transradial and transfemoral access in ACS, ultimately laying the foundation for modern guidelines prioritizing radial access to optimize patient safety.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

Why is the radial artery anatomically preferred over the femoral artery for minimizing bleeding complications during cardiac catheterization in ACS patients, and what bedside test is classically performed prior to its access?

Key Response

The radial artery is superficial and easily compressible against the radius bone, facilitating rapid hemostasis. In contrast, the femoral artery is deeper and carries a significant risk of concealed, life-threatening retroperitoneal bleeding. The Allen test is classically performed to confirm adequate collateral blood flow to the hand via the ulnar artery before radial access is attempted.

Resident

In managing a patient presenting with an acute STEMI, how should the findings of the RIVAL trial influence your choice of vascular access, assuming your catheterization lab has high radial volume?

Key Response

While the RIVAL trial showed no significant difference in the primary composite endpoint for the overall ACS cohort, it demonstrated a significant reduction in mortality and ischemic events specifically in the STEMI subgroup and at high-volume radial centers. Therefore, radial access is the preferred approach for STEMI management when operator expertise is available.

Fellow

The RIVAL trial revealed a mortality benefit for radial access specifically in the STEMI subgroup but not in the NSTEMI/UA cohort. What are the mechanistic and pharmacological factors that explain this divergent outcome?

Key Response

STEMI patients generally have a higher acuity of illness and often receive more aggressive, potent antithrombotic and antiplatelet regimens upfront (such as GP IIb/IIIa inhibitors), giving them a higher baseline risk for catastrophic bleeding. By virtually eliminating access-site bleeding via the radial approach in this highly anticoagulated subset, the reduction in bleeding translates more directly into a measurable survival advantage compared to lower-risk NSTEMI/UA patients.

Attending

Given the strong operator volume-outcome interaction demonstrated in the RIVAL trial, how should a primarily femoral-trained attending safely transition their practice to a radial-first approach without compromising patient safety during the learning curve?

Key Response

RIVAL highlighted that the benefits of radial access are highly dependent on operator and center volume. Attendings must balance the ethical imperative to adopt an evidence-based safer technique with the inherent risks of a learning curve. This requires structured proctoring, initially selecting stable non-complex cases for radial access, and maintaining a low threshold to cross over to femoral access to avoid prolonged procedural ischemic times.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

The RIVAL trial utilized a primary composite endpoint of death, MI, stroke, or non-CABG major bleeding. From a methodological standpoint, how did the inclusion of non-access-site bleeding and broad ischemic events dilute the measurable treatment effect of the access-site intervention?

Key Response

The intervention (radial access) has a targeted biological mechanism: preventing access-site complications. By pooling access-site bleeding with non-access-site bleeding (e.g., gastrointestinal hemorrhage) and systemic ischemic events into a single composite primary endpoint, the study introduced substantial statistical noise. This dilution of the specific treatment effect made it highly challenging to achieve statistical significance for the primary outcome.

Journal Editor

A critical reviewer of the RIVAL trial would point to the asymmetrical crossover rate, with 7.6% crossing from radial to femoral versus only 2.0% from femoral to radial. How does this asymmetry bias the intention-to-treat (ITT) analysis regarding the safety profile of the radial approach?

Key Response

In a strict ITT analysis, patients randomized to the radial arm who crossed over to the femoral arm (often due to radial spasm or anatomical tortuosity) had any subsequent femoral access-site complications attributed to the radial group. This asymmetrical crossover biases the results toward the null and potentially underestimates the true safety and efficacy of successful radial access.

Guideline Committee

How did the subgroup findings of the RIVAL trial regarding access-site complications and STEMI mortality, in combination with subsequent trials, influence the current ACC/AHA and ESC guidelines regarding the Class of Recommendation for vascular access in ACS?

Key Response

RIVAL provided pivotal evidence that radial access significantly lowers major vascular access-site complications and suggested a mortality benefit in STEMI and high-volume centers. Combined with subsequent trials like MATRIX, this compelling evidence led both the ACC/AHA and ESC to upgrade radial access to a Class I recommendation (Level of Evidence A) over femoral access for patients with ACS undergoing invasive management.

Clinical Landscape

Noteworthy Related Trials

2012

RIFLE-STEACS Trial

n = 1,001 · JACC

Tested

Radial access

Population

Patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI

Comparator

Femoral access

Endpoint

30-day net adverse clinical events (NACE)

Key result: Radial access significantly reduced 30-day NACE, primarily driven by remarkably lower rates of major bleeding and cardiac death.

2015

MATRIX Trial

n = 8,404 · Lancet

Tested

Radial access

Population

Patients with acute coronary syndrome undergoing invasive management

Comparator

Femoral access

Endpoint

30-day MACE (death, MI, stroke) and NACE (MACE or major bleeding)

Key result: Radial access significantly reduced net adverse clinical events and major bleeding, along with a reduction in all-cause mortality compared to femoral access.

2019

SAFARI-STEMI Trial

n = 2,292 · JAMA

Tested

Radial access

Population

Patients with STEMI undergoing primary PCI

Comparator

Femoral access

Endpoint

30-day all-cause mortality

Key result: The trial was stopped early for futility, showing no significant difference in 30-day all-cause mortality between radial and femoral access in contemporary practice.

Tailored to your role

Want this tailored to you?

Add your specialty or training stage to get role-specific takeaways and more questions.

Personalize this analysis