• Radial to Femoral Access-Site Crossover in Invasive ACS Procedures Did Not Increase Risk in MATRIX Trial

    Access-site crossover from radial to femoral access in patients with acute coronary syndrome (ACS) undergoing invasive management did not appear to increase risk of major cardiovascular and clinical events in the MATRIX trial, despite a greater risk of bleeding.

    The findings came from a prespecified subanalysis of MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) Access – a randomized, superiority, multicenter trial run across Italy comparing radial versus femoral access in patients with ACS with or without ST-segment elevation (STEMI), undergoing invasive management.

    They were published online Monday in the Feb. 22 issue of JACC: Cardiovascular Interventions by lead author Felice Gragnano, MD, from the Universities of Bern, in Switzerland, and Campania in Italy, and colleagues.

    European and U.S. professional societies currently recommend the radial artery as the default vascular access site for the invasive management of patients with ACS because it is shown to reduce the risk of major bleeding, vascular complications and all-cause mortality compared to femoral access.

    However, in up to 10% of patients, technical difficulties related to radial intervention mean crossover to femoral access is required, the researchers noted. For these patients, whether the crossover from radial to femoral access site negatively affects outcomes compared with primary successful femoral access has remained unclear, they said.

    In the MATRIX trial analysis, they, therefore, assessed incidence, characteristics and prognostic implications of access-site crossover in 8,404 patients with ACS undergoing invasive management by randomly allocated radial (4,197 patients) or femoral (4,207 patients) access.

    Co-primary outcomes at 30 days were major cardiovascular events (MACE) – a composite of death, myocardial infarction (MI) or stroke – and net adverse clinical events (NACE), a composite of MACE or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. Secondaries included each component of the co-primary outcomes, cardiovascular death, access site-related and non-access site-related bleeding events, and definite or probable stent thrombosis.

    The patients were categorized into four groups, the first of which was radial crossover if the operator failed to start or complete the procedure via the randomly assigned radial access and required crossover to femoral or brachial access – accounting for 183 patients, 4.4% of the radial group.

    The second was femoral crossover to radial or brachial if the randomly assigned femoral access had failed – 108 patients, 2.6% of the femoral group. Third and fourth were successful radial access (4,014 patients) and successful femoral access (4,099 patients).

    Patients who underwent crossover from radial to the ulnar or contralateral radial arteries, or from femoral to the contralateral femoral artery (internal crossover) were not considered as crossover. 

    Access-site management during and after the procedure was left to the discretion of the treating physician, and reasons for crossover were categorized as one of the following: access site not attempted for any reason, issues in arterial puncture or sheath insertion, failure to complete coronary angiography, or failure to complete percutaneous coronary intervention (PCI).

    Clinical outcomes at 30 days with respect to fatal, ischemic and bleeding endpoints were “seemingly worse” in both the radial and femoral crossover groups compared with those who had successful primary access, according to unadjusted outcomes.

    The researchers report 13.7% incidence rate in the MACE endpoint for radial crossover patients and 17.5% for NACE, compared to 8.6% and 9.5%, respectively, in the successful radial access group, and 10% and 11.4%, respectively, in the successful femoral access group.

    However, after multivariate-adjustment, the risks did not differ between patients undergoing radial crossover and those who had successful radial access – not for MACE (adjusted rate ratio [adjRR]: 1.25; 95% confidence interval [CI]: 0.81 to 1.93; p = 0.32), nor for NACE (adjRR: 1.40; 95% CI: 0.94 to 2.06; p = 0.090), or their individual components.

    This was despite the fact radial crossover was associated with a significantly higher bleeding risk, including access site-related BARC type 2, 3, or 5 events (adjRR: 6.65; 95% CI: 3.60 to 12.26; p < 0.001) and surgical access site repair or transfusions (adjRR: 2.60; 95% CI: 1.01 to 6.67; p = 0.047).

    Compared with successful femoral access, radial crossover patients had an adjusted risk ratio for MACE of 1.17 (95% CI: 0.76 to 1.81; p = 0.47), and for NACE of 1.26 (95% CI: 0.86 to 1.86; p = 0.24).

    “Their individual components did not differ between the radial crossover group and the successful femoral access group,” the researchers said. “The overall bleeding risk was also similar in the 2 groups, yet the risk for access site-related BARC type 2, 3, or 5 bleeding was higher in patients with radial crossover (adjRR: 1.87; 95% CI: 1.08 to 3.26; p = 0.026).”

    Conversely, femoral crossover remained associated with a significantly increased risk of MACE compared to successful femoral access (adjRR: 1.84; 95% CI: 1.18 to 2.87; p = 0.007) and for NACE (adjRR: 1.69; 95% CI: 1.09 to 2.62; p = 0.019), as well as death, stroke, urgent target vessel revascularization, and definite or probable stent thrombosis after multivariate adjustment. 

    Bleeding events between these groups did not differ.

    “Radial access failure and subsequent crossover to femoral access abolishes the peri-procedural bleeding benefit associated with radial over femoral interventions but does not expose patients to a higher risk for MACE or NACE compared with successful radial or femoral access,” the researchers concluded.

    “In turn, femoral access failure and subsequent crossover to radial access remained associated with worse fatal and nonfatal ischemic outcomes, particularly among patients with STEMI, which could not be explained by measured patient characteristics.”

    They went on to call for prospective and adequately powered studies to clarify the prognostic implications of access-site crossover in ACS patients undergoing invasive management, as well as the development of new standardized algorithms or tools which can predict crossover risks.

    An accompanying editorial led by John W. Hirshfeld Jr., MD, from the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, notes that the findings show crossing over is “undesirable.”

    “The ideal strategy is to identify a particular patient’s optimal access site before the procedure,” they said, adding that difficult femoral access is generally easy to identify. Still, difficult radial access is trickier to identify before making an attempt, they said.


    Gragnano F, Branca M, Frigoli E, et al. Access-Site Crossover in Patients With Acute Coronary Syndrome Undergoing Invasive Management. JACC Cardiovasc Interv 2021;14:361-73.

    Hirshfeld JW, Faxon DP, Williams DO. Impact of Crossover: A Consideration for Initial Access Site Selection. JACC Cardiovasc Interv 2021;14:374-7.

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