Validated ARC-HBR Criteria Highlight ‘Eye-opening’ Proportion of PCI Patients at Risk

Patients at high bleeding risk (HBR) as defined by an academic research consortium (ARC) make up about 40% of the PCI population and are at an increased risk of both bleeding and ischemic events at 1 year, according to an observational validation study.

The ARC-HBR criteria, comprised of 20 major and minor clinical variables, were originally presented at EuroPCR last year and simultaneously published in Circulation. 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.

For the validation, published online last month ahead of print in EuroIntervention, Yasushi Ueki, MD (University of Bern, Switzerland), and colleagues included 12,121 patients from the Bern PCI Registry treated between 2009 and 2016. A total of 39.4% were identified as HBR, and these patients were older, more commonly female, and had more risk factors for atherosclerotic cardiovascular disease and comorbidities.

At 1 year, the HBR patients had increased risks of the primary endpoint of BARC 3 or 5 bleeding (6.4% vs 1.9%; P < 0.001) and of the device-oriented composite endpoint that included cardiac death, target-vessel MI, and target lesion revascularization (12.5% vs 6.1%; P < 0.001).

Patients at high bleeding risk had an increased risk of BARC 3 or 5 bleeding when considering all-cause death as a competing risk (HR 3.44; 95% CI 2.80-4.17). Additionally, the risks of BARC 3 or 5 bleeding and the device-oriented composite gradually increased as function of the ARC-HBR score (P < 0.001 for both).

Compared with the PRECISE-DAPT and PARIS bleeding risk scores, the ARC-HBR criteria were found to have higher sensitivity but lower specificity for BARC 3 or 5 bleeding. The C-statistics were comparable.

Comparison of Available HBR Estimators for BARC 3 or 5 Bleeding

A ‘Pragmatic’ Approach

“The ARC-HBR criteria represent a completely novel and very, very pragmatic and consensus-based approach to how one could predict bleeding,” senior author Lorenz Räber, MD, PhD (University of Bern, Switzerland), told TCTMD.

Experts might not be surprised by just how many PCI patients are at high bleeding risk, he said, but many practicing cardiologists might find the 40% figure identified here as high. “This is a substantial proportion of our patients undergoing PCI,” he pointed out.

As for the ARC-HRB criteria themselves, Räber said these data confirm their validity, but that “if you look at the individual characteristics and you study their individual prediction of bleeding, not every criterion is as good as the consensus would believe, so it clearly requires a certain fine-tuning.” For example, chronic anticoagulant use is listed major criterion but BARC 3-5 bleeding occurred only in 2.5% of patients taking anticoagulants, and modest renal failure—considered a minor criterion—was associated with bleeding rates concurrent with the other major criterion, he said.

Ultimately, these criteria “are comparable in terms of bleeding prediction to existing scores like the PRECISE DAPT or the PARIS scores,” Räber observed. “What we can do with these risk factors is we can safely predict patients that will not bleed, so if you do not fall under the category of a high-bleeding-risk patient, you can be very, very sure that he will not bleed. Conversely, if he fulfills the criteria for high bleeding risk, the positive predictive value is really limited. . . . Nevertheless, bleeding avoidance strategies remain of utmost importance to avoid bleeding.”

The next step, he concluded, will be to study how a risk score can be used to tailor the duration of dual antiplatelet therapy.

Highlighting the HBR Cohort

Commenting on the results for TCTMD, Ashish Pershad, MD (Banner - University Medicine Heart Institute, Phoenix, AZ), said he was happy to see a validation of the ARC-HBR.

The study is “a good first take at the patient population that is currently being underrecognized and undertreated in the cath lab with objective endpoints,” he observed. “The way it moves the needle is it makes people realize that nearly 40% of patients that come to our cath lab are HBR patients, and these HBR patients need to be handled with care because they are frail and fragile.”

A benefit of the criteria is that “seemingly minor laboratory abnormalities” that wouldn't alarm most clinicians are now validated minor risk factors that can substantially affect mortality risk, he said. “This is eye-opening to clinicians about how to handle these patients.”

He agreed with Räber in that ARC-HBR is not likely to be more advantageous than calculating a PRECISE-DAPT or PARIS score, but also said this “validates the ARC consensus criteria as being something that can be then looked at prospectively in a future study. I don't think based on this information we are going to suddenly use this as the preferred tool over PRECISE DAPT or PARIS. . . . The key is that it's got people's attention to this group of patients.”

Clinicians can “do all the right things” like using transradial access, minimizing the quantity of dye, optimizing PCI with adequate stent postdilatation, properly prepping the artery for deployment of the stents, and imaging at the conclusion of the procedure, according to Pershad. “You need to double down and do a really good job in the cath lab because you know that not doing a good job for these patients will have catastrophic consequences, because not only will they bleed more but they will also have a higher chance of mortality at 1 year.”

From here, Pershad said he would like to see a randomized trial comparing HBR with non-HBR patients using the ARC-HBR criteria “to determine whether this truly is a graded risk and to what extent it is responsible for incremental mortality in these patients.”

As opposed to a binary or dichotomous score, assessing bleeding risk by several criterion can be more challenging, Pershad noted. “The other thing about risk is [that it] is never constant. . . . Therefore, it requires individualization of care and recognition that a score is a snapshot in time, whereas the risks to a patient are dynamic and change over time.”