New Clarity on Patients at High Risk for Bleeding After PCI

PARIS, France—An academic research consortium (ARC) has waded into the question of how to precisely identify patients at high risk for bleeding when undergoing PCI, a definition that so far has lacked consistency.

A new consensus statement, which was presented at EuroPCR 2019 and published simultaneously in Circulation last week, lists 20 major and minor clinical variables. Patients are considered high risk for bleeding—defined as a BARC 3 or 5 bleeding risk ≥ 4% and/or a ≥ 1% risk of intracranial hemorrhage (ICH) at 1 year—if they meet one major or two minor criteria.

“We think there are roughly 20% of PCI patients who are high bleeding risk when they undergo angioplasty,” said lead author Philip Urban, MD (La Tour Hospital, Geneva, Switzerland and Cardiovascular European Research Center, Massy, France), during a press conference highlighting the new definitions from the Academic Research Consortium-High Bleeding Risk (ARC-HBR) group. “Therefore, it’s important to know who they are so that we can then tailor and assess treatments for that particular group of patients,” he stressed.

From a research perspective, Urban said there have been a number of clinical trials focusing on the high-risk-bleeding patients, and that even more are ongoing, but “there is a lack of consensus about how to define these patients.” The absence of agreed-upon definitions limits the design of future studies, as well as the interpretation of existing trials. “And it doesn’t help clinicians make decisions because they are confused about who is high bleeding risk,” said Urban.

• The major criteria for high bleeding risk at the time of PCI now include the following:
• Anticipated use of long-term anticoagulation
• Severe or end-stage chronic kidney disease (estimated glomerular filtration rate < 30 mL/min)
• Anemia, defined as hemoglobin < 11 g/dL
• Spontaneous bleeding requiring hospitalization or transfusion in the past 6 months (or at any time, if recurrent)
• Moderate of severe thrombocytopenia
• Chronic bleeding diathesis
• Liver cirrhosis with portal hypertension
• Active malignancy (excluding nonmelanoma skin cancer) within the past 12 months
• Previous spontaneous ICH; previous traumatic ICH within the past 12 months; presence of brain arteriovenous malformations; or moderate or severe ischemic stroke within the past 6 months
• Nondeferrable major surgery on dual antiplatelet therapy
• Recent major surgery or major trauma within 30 days of PCI

In isolation, said Urban, any of the above criteria place the patient at increased risk of major bleeding and/or ICH following PCI.

There are other minor criteria; in isolation these increase the risk of bleeding, but not beyond the limits established by the ARC-HBR consortium. A patient is considered high bleeding risk with two minor criteria, and such criteria include older age (≥ 75 years), moderate chronic kidney disease, hemoglobin levels of 11-12.9 g/dL for men and 11-11.9 g/dL for women, nonmajor spontaneous bleeding requiring hospitalization or transfusion in the past 12 months, long-term use of oral nonsteroidal anti-inflammatory drugs or steroids, and any ischemic stroke not considered major.

The ARC-HBR definition is likely to require validation and further calibration as more data accumulate, said Urban. Nonetheless, he said, it provides a “much-needed framework” for moving the field forward.

The ARC-HBR consortium considered the presentation of ACS as part of the criteria for high bleeding risk, particularly in patients treated with a glycoprotein IIb/IIIa inhibitor plus prasugrel. In the end, said Urban, the aggressive antithrombotic regimen rather than the clinical presentation was considered the source of bleeding risk. Frailty was also debated as a potential variable increasing bleeding risk, but defining frailty was a difficult task so they opted to forgo including it as criteria at this juncture. Moreover, some of their other criteria, such as age, partially capture frailty as a risk factor.

Race was also debated as a consideration, given that it’s become evident that people from Asia, particularly Japan and Korea, have a higher bleeding risk, said Urban. At this point, though, the group felt they didn’t have sufficient data to include race/ethnicity as part of their major and minor criteria for bleeding risk.

Philip MacCarthy, MBChB, PhD (King’s College Hospital, London, England), one of the panelists during the EuroPCR session, said the patient at high risk for bleeding is the future. “This is now the kind of patient we’re going to be treating more and more, and generations ahead of us are going to be treating,” he said. “I think [ARC-HBR definition] is extremely timely. There is a lot more work to be done to establish how we manage these patients, but this is an excellent start.”  

Next steps, which are already in the works, will involve identifying clinical trial characteristics best suited to the needs of patients at high bleeding risk and addressing the second part of equation, that being the risk of recurrent thrombotic events in PCI-treated patients, said Urban. Those consensus statements are expected to be ready in 2020.    

The 2-day meeting of the ARC-HBR group, which met in 2018 and was organized by the Cardiovascular European Research Center, included representatives from the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency.