Meta-analysis Pins Down Survival Benefit for Transradial Access

Patrice Wendling

August 31, 2022

A new patient-level meta-analysis shows lower 30-day mortality and major bleeding with transradial vs transfemoral access for coronary angiography or percutaneous coronary intervention, adding support to existing guidelines but leaving open the question of why patients live longer.

"The bleeding benefit with transradial access appears consistent across multi sensitivity and subgroup analyses, whereas the mortality reduction seems substantial, especially in patients with baseline anemia," reported Giuseppe Gargiulo, MD, PhD, University Federico II of Naples, Italy.

The results were presented in a hotline session at the European Society of Cardiology (ESC) Congress 2022 and published simultaneously in Circulation.

European and American guidelines endorse preferential use of transradial access (TRA) over transfemoral access (TFA), however, debate continues to swirl over a survival benefit because it has been seen in some but not all TRA trials, he noted.

The Radial Trialists' Collaboration took up the challenge, examining individual data from 21,600 patients (mean age, 64 years; 32% women) in seven contemporary trials over the last decade: COLOR, MATRIX, RIFLE-STEACS, RIVAL, SAFARI-STEMI, SAFE-PCI for Women, and STEMI-RADIAL.

The cohort was evenly divided between TRA and TFA for either percutaneous coronary intervention (75%) or coronary angiography (25%). Nearly all patients presented with acute coronary syndrome (ACS), of which 49% was non–ST-segment–elevation ACS (NSTEACS) and 46% ST-elevation myocardial infarction (STEMI).

In an intention-to-treat analysis, all-cause mortality at 30 days was 1.6% with TRA and 2.1% with TFA corresponding to a 23% relative risk reduction (hazard ratio [HR], 0.77; P = .012). The number needed to treat to prevent one death was 214.

The mortality benefit was consistent across subgroups, with the exception of baseline anemia. Patients with significant anemia (hemoglobin < 11 g/dL) had a 65% relative reduction in the risk for death and a number needed to treat of 20 compared with those with mild or no anemia (7.7% vs 1.7%; HR; 0.35; P = .003). "In secondary analyses, this effect remained significant, indicating that it was independent of the cutoff used," Gargiulo said.

The survival benefit was confirmed in the per-protocol and as-treated, percutaneous coronary intervention, ACS, and myocardial infarction cohorts. It mainly occurred in the first 2 days after the procedure and remained throughout the 30 days, he observed.

Major bleeding was also lower with TRA than with TFA, with a relative risk reduction of 45%, absolute reduction of 1.2% (1.5% vs 2.7%; P < .001), and number need to treat of 84. This benefit was consistent regardless of the bleeding definition used.

Transradial access was associated with fewer access-site major bleeds, vascular complications, and blood transfusions. The risk for net adverse clinical events was 20% lower (7.5% vs 8.1%; P < .001) and for major adverse cardiac and cerebrovascular events, 11% lower (6.0% vs 6.6%; P = .047).

Patients accessed transradially had shorter hospital stays but greater crossover rates.

But Why Is Survival Better?

A mediation analysis showed that the "survival benefit with transradial access is only partially mediated by major bleeding reduction," said Gargiulo, adding that additional access-site-related mechanisms are likely involved.

When asked during the panel discussion what else might be driving the benefit, he said that the investigators hypothesize that acute kidney injury plays a role as it has been associated with mortality in several studies comparing the two approaches. In addition, the MATRIX trial showed that TRA significantly reduced the incidence of acute kidney injury.

Asked for his thoughts on this question, invited discussant, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai in New York City, said that "I think that's as good a hypothesis as any."

Stone called the meta-analysis "impressive" and "very important" but also noted that the absolute mortality reduction of 0.5% was "modest."

Among key subgroups, however, patients with STEMI had an absolute mortality reduction of 1%, he pointed out. Although the test for interaction was not significant (P = .235), mortality in patients with stable or NSTEACS was very low without any real differences between radial and femoral access, suggesting that "pretty much all of the treatment benefit exists in the STEMI subgroup."

In addition to patients with significant anemia, mortality was also lower among patients for whom the operator had high vs lower radial volume (P for interaction = .012).

"These data strongly support radial intervention in these settings but provide some reassurance, predominantly to femoral operators or when transradial axis is difficult," Stone said.

There was no interaction whatsoever, however, in these subgroups in terms of bleeding, and "that's the first clue that perhaps bleeding is not explaining all of the morality benefit," he observed.

Instead, the interactions were with adjunct pharmacotherapy, where TRA reduced bleeding when dual vs single antiplatelet therapy was used and, even more importantly, when unfractionated heparin was used rather than bivalirudin.

"So we still have a ways to go in understanding the mechanisms underlying the mortality benefit of transradial access in select subgroups," Stone said.

But, there were some limitations, he added. There was substantial between-study heterogeneity in bleeding definitions and rates — "harmonizing the bleeding with a uniform definition might have improved precision." Also, 1-year or longer data were not available, and "it may take some time for the bleeding benefit to translate into reduced mortality."

During a press briefing before the formal presentation, Gargiulo said, "this meta-analysis provides evidence that transradial access should be considered the gold standard access site for percutaneous coronary procedures, particularly in acute coronary syndrome."

The study was funded by Bern University Hospital and the Cardiocenrol Ticino Institute, Switzerland. Gargiulo reports personal fees from Daiichi Sankyo. Stone reports no relevant financial disclosures.

Circulation. Published online August 29, 2022. Full text

Follow Patrice Wendling on Twitter: @pwendl.

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