ARC-HBR Defines High Bleeding Risk in PCI Patients

Patrice Wendling

May 30, 2019

PARIS — Amid increasing efforts to dismantle dual-antiplatelet therapy, an international consortium is standardizing the definition of high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention (PCI).

"We realized after LEADERS FREE and the ZEUS trial, there was a growing interest in people who really had been disregarded," lead author Philip Urban, MD, Hôpital de la Tour in Geneva, told | Medscape Cardiology. "Until then, everybody went ahead and designed his own trial with his own definitions and we realized we were running into a problem because we weren't speaking a common language."

Having a consistent definition of HBR is essential to interpreting data from clinical trials of stents and drug therapies and in daily practice, the authors say.

"These patients are common to our practice," coauthor Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York City, told | Medscape Cardiology. "As the complexity of our procedures is increasing, so are the patients with many comorbidities, and as soon as you add comorbidities, you're adding not only just ischemic risk, but also bleeding risk. So it becomes really, really important to evaluate patients in an equal footing with a standardized definition."

Based on consensus and a review of the literature, the 31-member Academic Research Consortium for High Bleeding Risk (ARC-HBR) group defines HBR as a BARC 3 or 5 bleeding risk of at least 4% at 1 year or an intracranial hemorrhage (ICH) risk of at least 1% at 1 year. Patients are considered at HBR if they meet at least one major or two minor criteria.

Major criteria for HBR are:

  • anticipated long-term anticoagulation after PCI

  • severe or end-stage chronic kidney disease (eGFR <30 mL/min)

  • anemia (hemoglobin <11 g/dL)

  • spontaneous bleeding requiring hospitalization or transfusion in the previous 6 months or at any time, if recurrent

  • moderate or severe thrombocytopenia (platelet count <100×109/L)

  • chronic bleeding diathesis

  • cirrhosis with portal hypertension

  • active malignancy in the previous 12 months

  • presence of brain arteriovenous malformation, previous spontaneous ICH at any time, previous traumatic ICH in the previous 12 months, moderate or severe ischemic stroke in the previous 6 months

  • nondeferrable major surgery on dual antiplatelet therapy (DAPT)

  • major surgery or major trauma in the 30 days before PCI

Minor criteria are:

  • age at least 75 years

  • moderate chronic kidney disease (eGFR, 30–59 mL/min)

  • hemoglobin 11.0 to 12.9 g/dL for men and 11.0 to 11.9 g/dL for women

  • spontaneous bleeding requiring hospitalization or transfusion in the previus 12 months not meeting the major criterion

  • long-term use of oral nonsteroidal anti-inflammatory drugs or steroids

  • any ischemic stroke at any time not meeting the major criterion

The statement was presented by Urban at the Congress of the European Association of Percutaneous Cardiovascular Intervention 2019 and published simultaneously May 22 in Circulation.

The decision to make age a minor criterion differs from the long-standing practice of using advanced age to deny entry into clinical trials. Advanced age is also the only variable in common between six different risk scores developed to predict long-term bleeding risk in patients taking antiplatelet therapy. Simply using advanced age, however, doesn't address the differences in the risk of bleeding between a very healthy 75-year-old individual and a patient of similar age who has a malignancy and just had a bleeding episode and is also anemic, observed Mehran.

"And why that's important is if we're rationing and shortening duration of DAPT, we better be doing it in the patients who are going to have a net benefit," she said. "If they're not at a high risk of bleeding, we shouldn't be reducing the duration of DAPT. And if we just use age and nothing else, we could be reducing DAPT in way too many patients and actually creating a hazard rather than a benefit."

Risk factors that didn't make it into this iteration include frailty, ethnicity, and acute coronary syndromes (ACS).

"I would think that frailty will find its way into this definition in the moderately near future, but for the moment we didn't think we had enough data to comfortably suggest one definition rather than another as the cut off," explained Urban.

The group also felt more data were needed before making a recommendation on ethnicity, despite an increasing amount of data suggesting that patients of Japanese or Korean ethnicity have a different trade-off between thrombosis and bleeding: "You seem to clot less and bleed more," he said.

As for ACS, the consensus was not to include it as an HBR criterion because the increased bleeding risk in ACS patients undergoing PCI is attributable to the use of more aggressive antiplatelet therapy rather than the ACS per se.

Of note, the ARC-HBR group created an app that physicians can use to quickly run through a patients' data and decide whether or not they are at HBR.

"But for clinical decisions, obviously, you also need to put thrombosis in the balance and we haven't done that yet. This is only half the story," Urban said. "So I don't think you can tell people, 'Run through the app, decide whether they're HBR, and then you've got a clear answer about your antiplatelet treatment.' That's not true. It will have to be matched against the thrombosis risk. We're working on that and hope to come up with something by the end of the year, but we're not there yet."

Limitations of the current document, Urban said are that the cut-off values for 1-year BARC 3 or 5 and ICH are arbitrary, the definition is binary, and they were unable to create a point-based score that would take into account the relative weight of each HBR criteria.

"Our hope is that all trials focusing on HBR patients would collect all the information, so that they can then tell us how this works," Urban said. "First of all, it would help their trial to gain wide acceptance in terms of these are really the patients we're talking about. And, second, eventually it would mean that we could pool some of these data and if we have enough patients, we could use them to recalibrate, as needed, our definition. It's quite possible that we would then be gradually able to not only say 'yes or no you're HBR,' but then quantify it."

Urban reports receiving speaker and consulting honoraria from Biosensors-Europe, Sinomed, and Terumo; participating in paid review activities for Edward Lifesciences, Terumo, and Abbott Vascular; and serving as a medical codirector at the Cardiovascular European Research Center . Mehran reports consultant fees to her institution from Abbott and Spectranetics/Philips/Volcano; consulting fees from Boston Scientific, Cardiovascular Systems, Medscape, Siemens Medical Solutions, Regeneron Pharmaceuticals, Roivant Sciences, and Sanofi; being the spouse of a consultant for Abiomed and The Medicines Company; institutional research funding from AstraZeneca, Bayer, Beth Israel Deaconess Hospital, BMS, CSL Behring, Eli Lilly, DSI, Medtronic, Novartis Pharmaceuticals, and Orbus Neich; scientific advisory board fees from PLx Opco Inc, dba PLx Pharma Inc; scientific advisory board fees to her institution from Bristol-Myers Squibb; executive committee fees from Janssen Pharmaceuticals and Osprey Medical; speaker engagements for Abbott; equity from Claret Medical and Elixir Medical; and Data Safety Monitoring Board fees to her institution from Atermark Research Partners.

Circulation. Published online May 22, 2019. Full text

Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2019

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