RIVAL Confounds Transradial PCI
The randomized, controlled RIVAL trial, presented in April at ACC.11, was expected to show a bleeding reduction with using radial access for PCI in patients with acute coronary syndromes (ACS). While the trial did not achieve its anticipated primary endpoint, transradial PCI may continue to gain utilization momentum if physicians succeed in deciphering how the results could impact their practice.

Unraveling RIVAL

With the goal of assessing radial versus femoral access for PCI in ACS patients, the RIVAL investigators, led by Sanjit Jolly, MD, of McMaster University's Population Health Research Institute in Hamilton, Ontario, enrolled 7,021 patients from 158 hospitals in 32 countries and randomly assigned them to radial (3,507 patients) or femoral access (3,514).

For the primary outcome of death, MI, stroke or non-CABG major bleeding, the rates were 3.7 percent in the radial access arm compared with 4 percent in the femoral access arm.

"The RIVAL findings came as a surprise to many practitioners, when the primary endpoints were not met for the general study population," according to Christopher T. Pyne, MD, of the Lahey Clinic in Burlington, Mass. At the study's inception, the RIVAL investigators had a working hypothesis that the major bleeding rates in the femoral arm would be much higher than the ultimate outcomes. The big surprise of RIVAL was how well the operators performed the femoral cases, which is a positive thing for patients."

However, the findings showed a more than 60 percent reduction in major vascular complications in the transradial arm. At 30 days, 42 patients in the radial group had large hematomas compared with 106 in the femoral arm. Pseudoaneurysms needing closure also were lower in the radial group: seven versus 23 patients.

Jolly concludes the "major benefit of radial access is preventing vascular complications, which is an important issue for patients." RIVAL also revealed that patients prefer the radial approach, causing the investigators to speculate that the adoption rate will continue to rise.

"While we do not completely understand why the radial arm performed better with vascular complications, the results of RIVAL reveal a very positive trend for patients, as both procedures indicate low bleeding rates," says Pyne. "As physicians, we are more concerned with improving patient outcomes than politicizing techniques."

Bleeding risk

"There are multiple bleeding definitions from TIMI Major Bleeding, which is stringent, to the ACUITY definition, which is broader, but RIVAL used a definition that would capture serious and life-threatening bleeding from the OASIS trial," Jolly explains.

In the trial, access-site bleeding accounted for one-third of the overall bleeds in these ACS patients, and two-thirds of the bleeding occurred due to gastrointestinal bleeding and other sources.

Sunil V. Rao, MD, of Durham VA Medical Center in N.C., who worked on the consensus report of the Bleeding Academic Research Consortium (BARC), which is looking to standardize bleeding definitions, says the consortium may help clarify the plethora of definitions. However, he says that bleeds should not be qualified as major or minor because of their severity to the patient.

"If the ACUITY bleeding definition that focuses on bleeds beyond the access-site had been employed in RIVAL, the transradial approach may have shown a benefit," Rao says. He adds that proper pharmacoinvasive therapy remains "tremendously important," and a complementary technique of employing bivalirudin (Angiomax, The Medicines Company), in addition to the transradial approach may ultimately result in the best patient outcomes.

"We're becoming increasingly aware of the potential for non-access site bleeding," says Pyne. "We previously thought that wrist access prohibited bleeding, but now we are becoming more cognizant of patients at risk for bleeding regardless of access site."

Interestingly, only 3 percent of the RIVAL population received bivalirudin, leading many physicians to speculate that the bleeding rates could have been equivalent between the femoral and radial access arms with greater usage of bivalirudin.

"Bivalirudin has been shown to be safer than heparin plus glycoprotein IIb/IIa inhibitors, but the rate the IIb/IIa inhibitors was only 25 percent in the trial," Jolly notes. Currently, there has not been a head-to-head trial of bivalirudin compared with a low modern dose of heparin monotherapy or selective use of IIb/IIa inhibitors.

Jolly recommends a holistic approach to bleeding reduction, which may utilize the transradial approach to reduce access-site bleeds and safer thrombotic regimens to reduce non access-site bleeds.

Procedure volume & STEMI

Of the six pre-specified RIVAL subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centers and in patients with STEMI, particularly for mortality.

High-volume centers and high-volume operators performed better with the transradial approach. "Institutional volume was as important as the individual operator volume," Pyne says.  

"We know that the more procedures you perform, the better you get, particularly with the transradial approach," says Jolly, "but there is no identifiable number of procedures that makes an operator proficient."

The median annual case volume per operator in RIVAL was 300, which is "significantly higher than the vast majority of operators in the U.S.," says Rao. While Jolly acknowledges that the results might not be currently translatable due to lower operator volumes in the U.S., he hypothesizes that transradial PCI volume for U.S. interventionalists might be comparable in the next five to 10 years.

For the mortality benefit seen in STEMI patients, Jolly acknowledges his lack of explanation and cautions others against hypothesizing too much about a study subgroup. However, this population receives more potent antithrombotic and antiplatelet therapies.

Also, the more experienced operators in RIVAL more oft opted for the transradial approach for STEMI patients, which might lead to superior outcomes. There are several ongoing trials specifically assessing transradial PCI for STEMI, promising more insight in the next two years.

Rao concludes that the vascular complication rates, coupled with patient preference and the mortality benefit for STEMI patients, indicate that radial PCI may be "ready for primetime."