BARC Criteria Validated Against Existing Bleeding Definitions

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Bleeding events as defined by Bleeding Academic Research Consortium (BARC) classifications are independently associated with an increased risk of 1-year mortality across a wide spectrum of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), according to a study published online, February 17, 2012 ahead of print in Circulation.

For the study, Adnan Kastrati, MD, of the Deutsches Herzzentrum (Munich, Germany), and colleagues aimed to validate the BARC unified definitions of bleeding in a pooled analysis of 12,459 patients from 6 randomized trials. Patients in the trials were recruited between 2000 and 2010. All bleeding events were assessed using the BARC criteria, the Thrombolysis in Myocardial Infarction (TIMI) criteria and the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial criteria.

When bleeding events were classified, 3.0% had an event according to the TIMI definition (n = 374), 3.9% according to REPLACE-2 criteria (n = 491), and 9.9% according to BARC criteria (n = 1,233). Of those with BARC-defined bleeding events, 5.4% had bleeding that was class 2 or greater (n = 679).

Over the first year following PCI, there were 340 deaths (2.7%). Each set of bleeding definitions demonstrated an independent association between bleeding and 1-year mortality (table 1).

Table 1. One-Year Mortality After Bleeding Events

One-year mortality differed slightly from 9.3% in patients with a BARC bleeding class ≥ 2 to 11.7% in patients with TIMI-defined major bleeding, demonstrating an increased risk across all 3 bleeding definition criteria. Compared with patients with no bleeding, the risk of death ranged from more than 4 times in patients with a BARC bleeding class ≥ 2 to 5 times in those with TIMI defined bleeding (major and minor).

Furthermore, the 1-year mortality risk increased with bleeding event intensity per BARC classification (table 2).

Table 2. One-Year Mortality According to BARC Classification

Mortality risk in patients who experienced bleeding after PCI steadily increased through the first year post-procedure for all bleeding definitions (P < 0.001 for all).

Bleeding criteria had relatively low sensitivity and high specificity and accuracy overall with regard to 1-year mortality. BARC class 2 or greater had higher sensitivity compared with TIMI and REPLACE-2; however, “this was achieved at the cost of lower specificity,” according to the researchers.

Confirming the ‘Theoretical’

In a telephone interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), said that the pooled analysis is useful in validating the BARC definition in a real-world setting.

“The BARC definitions were really theoretical, to a certain extent, because they had not been tested,” Dr. Brener said. “It is nice to see that they correspond to real life and that they also predict outcomes, in this case death, which further enforces the fact that bleeding is a non-desirable outcome.”

The study may help to identify which class of bleeding, according to BARC definitions, is worth concentrating on in clinical practice, Dr. Kastrati told TCTMD in an e-mail communication.

“Considering the close association between occurrence of bleeding and prognosis, this finding may promote an increased awareness and more care for a portion of patients who are at increased risk for poor outcomes and who could have gone undetected using less sensitive bleeding classification systems,” he said.

Expand Areas of Validation

In an accompanying editorial, 2 members of the BARC writing committee, Sunil V. Rao, MD, of Duke University Medical Center (Durham, NC), and Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), said that although they “find a measure of comfort that the work of [this study] validates our efforts,” they are not surprised by the results.

Although the study is a “first step,” they write, the patient population must be expanded in future studies to include those with elevated troponin levels and STEMI. Specifically, Drs. Rao and Mehran would like to see future studies assessing “the prognostic impact of BARC bleeding across the spectrum of ischemic heart disease and across management strategies. In addition, it should be tested in the context of other invasive procedures such as CABG, endovascular procedures, and transcatheter valve procedures.”

Dr. Brener echoed this observation, pointing out that the analysis only looked at patients from trials with low event rates. “It would be nice,” Dr. Brener said, “to look at [these definitions] in a cohort of patients who are a little sicker.”

Future Use Likely

For now though, the overall outlook for the integration of BARC bleeding definitions is positive, particularly in the clinical trial setting.

“The field was looking for a unified definition because the TIMI classification is very strict and the REPLACE-2 definitions are way too lenient,” said Dr. Brener. “There was a need for one in the middle.”

The BARC definitions seem to fit the bill; however, because it is a much more detailed classification system, it will require a greater time investment to learn, Dr. Kastrati said. Despite this, he expressed hope that the present study will expand the use of the BARC bleeding definition criteria in clinical practice and serve as an impetus for further research in this field.

Study Details

Overall, 91.5% of patients had a coronary stent implanted (including 58% with DES) and 8.5% were treated with balloon angioplasty alone. The average age of patients was 67 years and women made up slightly less than a quarter of the overall cohort.

Note: Dr. Mehran is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Sources:
1. Ndrepepa G, Schuster T, Hadamitzky M, et al. Validation of the Bleeding Academic Research Consortium definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention. Circulation. 2012;Epub ahead of print.

2. Rao SV, Mehran R. Evaluating the bite of BARC. Circulation. 2012;Epub ahead of print.

 

 

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