New Score Can Identify ACS Patients at High Bleeding Risk

June 08, 2010

June 8, 2010 (New York, New York) — ACS patients at increased risk for bleeding and subsequent one-year mortality can be identified with a simple risk score based on six baseline measures plus anticoagulation regimen, and these patients can then be targeted for appropriate treatment strategies, a new study has shown [1].

"Such knowledge will aid the accurate prognostication of patients with ACS, facilitating appropriate personalized decision-making for the patient at high risk of bleeding and mortality," the authors conclude.

Better Than Previous Scores?

Noting that previous risk scores have been suggested for predicting bleeding, they point out that the C statistic from this analysis (0.74) is slightly higher than previous models, suggesting better discrimination.

The study, published in the June 8, 2010 issue of the Journal of the American College of Cardiology, was conducted by a team led by Dr Roxana Mehran (Columbia University Medical Center, New York).

Mehran commented to heartwire: "There are other good bleeding risk scores already available, but this one from ACUITY and HORIZONS AMI has the advantage of being very practical and easy to use and is based on two large contemporary trials with data from more than 17 000 ACS patients."

She noted that her team is now working to develop a simple bleeding risk calculator that will be able to be downloaded from their website within the next few months. "Doctors can download this onto their handheld devices and just tap in the relevant numbers, and it will give them a bleeding risk score, which will enable them to make a quick decision on how to tailor therapy."

She added that they also plan to look at the entire PCI population (not just ACS patients) and develop a risk score that takes into account both bleeding and ischemic risk.

In the paper, the researchers explain that hemorrhagic complications are an independent risk factor for subsequent mortality in ACS patients and in those undergoing PCI and represent a hazard equivalent to or greater than that for MI. While certain characteristics are known to be associated with an increased risk of bleeding--for example, old age, female sex, impaired renal function, and/or baseline anemia--the relative hazard of these factors and their interaction have been incompletely characterized.

They suggest that the development of a simple-to-use risk score for bleeding could standardize quality of care and patient outcomes. Risk stratification could also be employed to compare outcomes across clinical studies and institutions.

They therefore pooled the databases from the ACUITY and the HORIZONS-AMI trials, both comparing bivalirudin with heparin plus a GP IIb/IIIa blocker in ACS patients, to develop such a risk score and test its performance.

Results showed that of the 17 421 patients included in the two trials, non–CABG-related major bleeding within 30 days occurred in 744 patients (7.3%). Six independent baseline predictors for major bleeding were identified--female sex, advanced age, elevated serum creatinine and white blood cell count, anemia, non–ST-segment-elevation MI, or ST-segment-elevation MI. Treatment with heparin plus a IIb/IIIa inhibitor rather than bivalirudin alone was also a predictor.

The risk score differentiated patients with a 30-day rate of non–CABG-related major bleeding ranging from 1% to over 40%. Other results showed that major bleeding was an independent predictor of a 3.2-fold increase in mortality, and this link to mortality risk was strongest for non–CABG-related TIMI-defined major bleeding followed by non-TIMI major bleeding with or without blood transfusions, whereas isolated large hematomas and CABG-related bleeding were not significantly associated with subsequent mortality.

"Enormous Variation" in Bleeding Risk

The authors note that their study has documented an "enormous variation" in the likelihood for individual patients to develop a non–CABG-related major bleed within 30 days of presentation with ACS. They add that while some of the risk factors for bleeding were known before, a higher white blood count, perhaps reflecting the influence of systemic inflammation, is novel and deserves future investigation.

They point out that the rates of non–CABG-related major bleeding were higher in patients enrolled with STEMI than with NSTEMI (6.2% vs 3.8%, respectively), although major bleeding was increased in NSTEMI patients with raised biomarkers at baseline. They suggest that the increased rate of bleeding in patients with STEMI might reflect the urgency of care provided, more frequent use of venous sheaths, unadjusted patient comorbidities, the more frequent use of a 600-mg loading dose of clopidogrel, or different GP-IIb/IIIa-blocker regimens.

Don't Withhold Clopidogrel Because of CABG Concerns

The authors also say that their finding that CABG-related major bleeding did not significantly predict subsequent mortality is important, because medications that might decrease PCI-related ischemic complications but increase surgical bleeding (eg, thienopyridines) are often withheld from patients with ACS until angiography confirms a likely nonsurgical management strategy. They suggest that with this new information, thienopyridine agents should be administered as early as possible before cardiac catheterization (in the ambulance or emergency room), so they might reach their maximal effect in patients undergoing PCI. But they add that the relationship between the severity of CABG-related bleeding and nonfatal clinical outcomes should be further assessed in future studies.

Editorial: Radial Access May Be Better Focus

In an accompanying editorial [2], Dr Jeffrey Brinker (Johns Hopkins Hospital, Baltimore, MD) suggests that the greatest opportunity to reduce bleeding and its sequelae may be with the use of radial- as opposed to femoral-arterial access for PCI. He points out that radial access has been associated with marked reductions in bleeding without a sacrifice in procedural success or increase in ischemic complications, and this approach might allow for more aggressive adjunctive antithrombotic therapy as well.

Brinker concludes: "Although we have been taught much from the bivalirudin trials, there is considerably more to learn about PCI technique and adjunctive pharmacotherapy before its safety and effectiveness can be optimized. We know the score, but the game is not over."

Mehran is on the speakers’ bureau for the Medicines Company, the maker of bivalirudin; Cordis; and Boston Scientific. She has received research support from Bracco and Bristol-Myers Squibb/Sanofi-Aventis and honoraria from Abiomed, Abbott, Accumetrics, AlphaMedica, AstraZeneca, Bristol-Myers Squibb/Sanofi-Aventis, Bracco, Cardiva Medical, Daiichi Sankyo/Eli Lilly, Gilead, Guerbet, Regado Biosciences, and Therox. Disclosures for the coauthors are listed in the paper. Disclosures for Brinker are not provided.

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