Less Death, Major Bleeding With Transradial Access: Meta-analysis

BARCELONA, Spain—Transradial access for coronary angiography or PCI is associated with a significantly lower risk of all-cause mortality compared with transfemoral access, as well as a lower risk of major bleeding, a new patient-level meta-analysis shows.

The survival benefit observed was only partially explained by the reduction in major bleeding, however, and investigators suspect additional access site-related mechanisms are involved. Giuseppe Gargiulo, MD, PhD (University Federico II, Naples, Italy), who led the meta-analysis, said the additional benefit may stem from reductions in acute kidney injury with transradial access.

“Indeed, from the MATRIX trial, the largest trial in ACS available and included in this meta-analysis, we previously demonstrated that transradial access significantly reduces the rates of acute kidney injury,” Gargiulo told TCTMD. “It’s known from several studies—randomized and observational studies—that acute kidney injury is associated with mortality. We hypothesize that it could play a crucial role.”

The meta-analysis from the Radial Trialists’ Collaboration, which was presented today during a Hot Line session at the European Society of Cardiology (ESC) Congress 2022 and published simultaneously in Circulation, was not intended to uncover those additional mechanisms, however.

Instead, said Gargiulo, it was meant to provide greater clarity around whether transradial access reduces the risk of death compared with femoral access. Gargiulo said their results provide yet more evidence that transradial access should remain the gold-standard access site for PCI, particularly for ACS patients.

Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), the scheduled discussant following Gargiulo’s presentation, said there is little doubt that transradial access reduces bleeding, but added that there has been some question as to whether it is associated with lower mortality.

“Some studies have said yes, other studies have said no,” said Stone. “Studies have a predominance of this effect in patients with STEMI, but it really wasn’t clear.”  

Mortality Reduced Nearly 25%

To answer the mortality question, the researchers turned to seven trials, among them COLOR, MATRIX, RIFLE-STEACS, RIVAL, SAFARI-STEMI, SAFE-PCI for Women, and STEMI-RADIAL. In total, 21,600 participants (mean age 63.9 years; 31.9% female) were included, with an equal split of patients randomized to transradial or transfemoral access for either PCI (75.2%) or coronary angiography (24.8%). ACS was the predominant clinical presentation, 48.6% presenting with NSTE ACS and 46.2% presenting with STEMI.  

At 30 days, all-cause mortality was 23% lower with transradial access (1.6% vs 2.1%; P = 0.012). The number needed to treat to prevent one death was 214. The mortality benefit was consistent across subgroups, except for the presence of baseline anemia. In those with significant anemia, transradial access was associated with a 65% reduction in all-cause mortality but no benefit was seen in those without baseline anemia (P = 0.003 for interaction).

Major bleeding was 45% lower with transradial access than with the transfemoral approach (1.5% vs 2.7%; P < 0.001), and this benefit was consistent regardless of which major bleeding definition was used. Additionally, transradial access was associated with few instances of access site-related major bleeding, vascular complications, and blood transfusions. It was also associated with a shorter hospitalization stay. Net adverse clinical events (NACE) were 20% lower with the transradial approach (7.5% vs 9.1%, P < 0.001).

“The bleeding reduction with transradial access appears consistent across multiple secondary analyses, while the mortality reduction seems substantial, especially in patients with significant baseline anemia,” said Gargiulo during a press conference announcing the results.

In the “mediation analysis” to account for the reduction in all-cause mortality with transradial access, major bleeding, as noted, only partially explained the benefit. Researchers did observe that the effect of transradial access on mortality occurred within 10 days—and mostly within the first 2 days—after the procedure, underscoring “the association with the invasive procedure.” 

Subgroup Analyses

Discussing the meta-analysis, Stone homed in on the various subgroups, including patients with and without STEMI. In STEMI patients, transradial access was associated with a 28% relative risk reduction in mortality, but this benefit was not seen in stable or NSTE ACS patients. Even though the test for interaction was not significant (P = 0.235), Stone said the subgroup finding suggests almost all of the treatment benefit is in the STEMI subgroup.

Similarly, a larger reduction in mortality with transradial access was seen in high-volume radial operators as opposed to low- or intermediate-volume operators (P = 0.012 for interaction), and there did not appear to be a benefit in patients treated with bivalirudin. In the bivalirudin/unfractionated heparin subgroup, however, the test for interaction was not significant (P = 0.536). 

Stone called the new meta-analysis “very impressive,” stating that it strongly supports use of transradial access, particularly among the highlighted subgroups who appeared to benefit more. He also said that it provides some reassurance that if operators can’t go radial for some reason, mortality may not be increased with femoral access in stable or NSTE ACS patients, those without anemia, or when bivalirudin is used.

The 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines recommend radial access as the standard approach for PCI, regardless of clinical presentation, unless there are overriding procedural considerations (class I, level of evidence A). The 2021 American College of Cardiology and American Heart Association guidelines also recommend a radial-first approach, both in ACS and stable ischemic heart disease patients undergoing PCI (class I, level of evidence A).