A novel score for predicting bleeding risk in patients with atrial fibrillation (AF), called HAS-BLED, performed better than any other contemporary score in a large cohort of anticoagulated patients; the score could become an important new clinical tool, say researchers [1]. This is the second validation of HAS-BLED; it was derived from and first validated in a European AF population last year [2].

“HAS-BLED is pragmatic; it’s an easy assessment and helps doctors to make an informed decision rather than guessing. It’s there to tell you, if the bleeding score is high enough, that more caution or more regular review of your patient is needed,” the lead author of the new paper, Dr Gregory YH Lip (University of Birmingham, UK), told heartwire . Lip points out that use of HAS-BLED is recommended in the new European Society of Cardiology (ESC) guidelines on AF as well in the latest guidance on AF from the Canadian Cardiovascular Society.

In an editorial accompanying Lip et al’s paper [3], Dr Stefan H Hohnloser (JW Goethe University, Frankfurt, Germany) says that HAS-BLED is an “important step” and “may indeed prove to be an important clinical tool to assess bleeding risk in AF patients.” However, he cautions that it remains to be seen how it will perform in daily routine practice and whether such a bleeding score–developed from data on patients receiving warfarin and other vitamin-K antagonists–can also be applied during use of the newer anticoagulants, which may have lesser bleeding risks.

A Simple Tool That Will Be Invaluable to Cardiologists

Lip says that optimum selection of patients with AF for anticoagulation therapy depends not only on assessment of their risk of stroke but also on identification of those at increased risk of developing bleeding complications. Hohnloser agrees, noting that currently anticoagulation therapy in AF is “underused, suboptimally applied, and often inappropriately discontinued . . . driven for a good part by the perceived bleeding risk associated” with warfarin therapy.

The HAS-BLED score is simple to remember, says Lip, and could become invaluable to cardiologists as, with the advent of newer oral anticoagulants, anticoagulation will migrate to become their responsibility. The first of these newer agents, dabigatran (Pradaxa, Boehringer Ingelheim), was recently approved for the prevention of stroke in patients with AF in the US and Canada, and other new drugs are also close to the market for this indication. Bayer and Johnson & Johnson announced today that they had filed for marketing approval for rivaroxaban with both the European Medicines Agency and the FDA for stroke prevention in AF.

“At the moment, if I make a decision on oral anticoagulation in a patient with AF, I write on the form, ‘needs warfarin,’ and that patient becomes the responsibility of the hematologist in the warfarin clinic, and I don’t have to worry about them. But we will soon be in the situation later this year where we will have new anticoagulants for AF, the first of which is likely to be dabigatran, and I, as a cardiologist sitting in my office, will have to make a decision: do I choose 110 mg or 150 mg (twice daily), or 75 mg if I am in the US?” he says.

He agrees with Hohnloser, however, that more work needs to be done to evaluate the score with these newer agents; for example, further validation of HAS-BLED in relation to dabigatran dose will be necessary, he says.

What Is the HAS-BLED Score and How Is It Calculated?

HAS-BLED stands for hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly (age over 65), and drugs/alcohol concomitantly; the maximum possible score is 9–with 1 point for each of the components (with abnormal renal/liver function, for example, possibly scoring two if both are present and similarly drugs/alcohol possibly contributing 2 points). “Drugs” refers to any medications that increase bleeding risk during anticoagulation, such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or even steroids on top of warfarin, and “alcohol” refers to alcohol abuse.

Lip, who is already using HAS-BLED in his clinic, says that although it is very easy to calculate and for the most part can be done mentally–or now with various iPhone apps–doctors must still use their initiative to a certain degree when scoring. For instance, although “elderly” is defined as over 65, this is really an assessment of “biological age,” or a guide to frailty, he says. “I have 90-year-old AF patients who are biologically 70 and 60-year-olds who are biologically 99.”

Physicians should also remember that the bleeding risk can be modified, and HAS-BLED “makes you think about things you can correct,” he notes. Stopping aspirin therapy is a good example of a way to reduce bleeding risk or controlling hypertension.

And there is no reason why HAS-BLED cannot be modified in the future if other risks for bleeding are identified, he notes. “There is always scope for refining various risk-assessment models, given how medicine evolves.”

He points to his own team’s modification of the CHADS2score for assessing stroke risk as an example of this. They refined it to become CHA2DS2-VASc, a new, more sensitive model including additional points for specific age categories, presence of vascular disease, and female gender.

HAS-BLED Better Than Other Bleeding Scores

In the new study, Lip and colleagues combined the SPORTIF III and V clinical trials and evaluated the predictive value of several bleeding risk-stratification schemas in the 7329 participating patients with AF. Lip points out that this is the largest validation of HAS-BLED to date and the first in an anticoagulated population: participants received either warfarin or fixed-dose ximelagatran 36 mg twice daily (ximelagatran was subsequently withdrawn following concerns about liver safety).

Of the tested schemas, the HAS-BLED score performed best, more accurately discriminating patients on the basis of bleeding risk, with a stepwise increase in rates of major bleeding with increasing HAS-BLED score (p for trend <0.0001).

Hohnloser says that this new validation of HAS-BLED confirms “the predictive power of this score,” which may be associated with better predictive accuracy than its predecessors.  On multivariate analysis, the new score added significantly to those models that already incorporated old models, but in contrast, none of the older models significantly contributed when inserted into a model that already contained the HAS-BLED score, he notes.

Diabetes, HF, or LV Dysfunction Identified as Risk Factors for Bleeding Too

Lip and colleagues say that their analysis also confirms the predictive value of previously identified risk factors for bleeding, including advanced patient age, concomitant use of aspirin or NSAID use during anticoagulation, and renal impairment.

In addition, diabetes mellitus and clinical heart failure or left ventricular systolic dysfunction were, for the first time, associated with an increased risk of bleeding during therapeutic anticoagulation in this cohort of patients. But this latter finding will require confirmation in other studies, Lip notes.

Lip has received funding for research, educational symposia, consultancy, and lecturing from different manufacturers of drugs used for the treatment of AF and thrombosis, including AstraZeneca, Boehringer, Bayer, Pfizer/Bristol-Myers Squibb, Biotronic, Astellas, Sanofi, Cardiome, and Merck, and is a clinical advisor to the UKNICE guidelines on AF management and a task force member of the 2010 ESC guidelines and the American College of Chest Physicians guidelines on antithrombotic therapy in AF . Disclosures for the coauthors are listed in the paper. Hohnloser has received research grants from St Jude Medical and Sanofi; is on the advisory boards for Sanofi, St Jude Medical, Boehringer Ingelheim, and Merck; and is on the speaker’s bureaus for Sanofi Aventis, St Jude Medical, Boehringer Ingelheim, Avyx, Cardiome, and Bristol-Myers Squibb.

Tags: ,

Leave a Reply

You must be logged in to post a comment.