For A-fib Patients, Aspirin on Top of Anticoagulation Raises Bleeding Risk

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Patients with atrial fibrillation (A-fib)—even those without cardiovascular disease—often receive aspirin in addition to oral anticoagulation, according to registry data published online July 16, 2013, ahead of print in Circulation. Although ischemic events were too rare in the study to tease out differences, the risk of bleeding was more than 50% higher in patients on dual therapy.

Researchers led by Eric D. Peterson, MD, MPH, of Duke University Medical Center (Durham, NC), looked at 10,126 patients with nonvalvular A-fib enrolled in the Outcomes Registry for Better Informed Treatment-Atrial Fibrillation (ORBIT-AF) registry at 176 US centers between June 2010 and August 2011.

In all, 7,347 patients (72.6% of the ORBIT-AF cohort) were on oral anticoagulation (93.4% warfarin, 6.6% dabigatran), with 2,543 patients (35%) also receiving aspirin. The majority of patients on aspirin received a low dose of 81 mg (88.5%), with a minority receiving 162 mg (0.5%), 325 mg (10.7%), or another dose (0.3%).

Aspirin Use Not Necessarily Connected to CAD

Substantial proportions of the dual therapy group had no history of CAD (39%) or ATRIA bleeding risk scores of 5 or higher (17%). Conversely, 37% of patients receiving oral anticoagulation alone had known CAD.

On multivariate analysis, the strongest predictors of use of dual therapy vs. oral anticoagulation alone were:

• History of CAD (adjusted OR 2.23, 95% CI 1.82-2.73)
• MACE (adjusted OR 1.56, 95% CI 1.05-2.32)
• DES (adjusted OR 1.53, 95% CI 1.17-2.01)
• Stroke/TIA (adjusted OR 1.45, 95% CI 1.25-1.67)

After adjustment for baseline differences, patients were at increased risk of major bleeding and bleeding-related hospital admissions at 6 months when aspirin was added to oral anticoagulation. Other outcomes were similar between the 2 groups (table 1).

Table 1. Adjusted 6-Month Outcomes

Ischemic event rates were low and equivalent in both groups at 6 months, though the paper cautions that the rarity of such events means that differences may not be detectable (table 2).

Table 2. Ischemic Event Rates at 6 Months

In a telephone interview, study coauthor Benjamin A. Steinberg, MD, of Duke University Medical Center, told TCTMD that the study speaks to several issues vexing clinical practice.

For one, there is a growing appreciation of the fact that aspirin carries risks as well as benefits. “[It was thought that] because we’d been using it so long . . . for all kinds of things that it was virtually harmless,” he said, noting aspirin’s over-the-counter availability. “More and more data suggest that while it is a very safe and effective medicine, just like any other medicine it does have side effects and risks. On a grand scale, when you look at many patients, you get to see that signal.”

Moreover, with rising prevalence of A-fib, Dr. Steinberg added, hopefully anticoagulant use is increasing. But questions remain about identifying and treating patients at risk of stroke.

Clinical Decision Making Far from Simple

Dr. Steinberg acknowledged that, given the lack of evidence in the literature, physicians face difficult decisions. “Particularly in the primary prevention cohort, it’s hard to make the case, based on our data, that everyone necessarily should be getting aspirin in addition to their anticoagulants,” he commented, noting that that this situation serves as an example of how even well-established drugs like aspirin are worthy of further study when applied to emerging populations.

Even for patients with CAD as well as A-fib, the answer is uncertain, Dr. Steinberg said. That population is not homogenous, and omitting aspirin may not be unreasonable in some cases, “depending on what you think their risk truly is,” he noted. “[This is based on] what their events were, whether you think the anticoagulant is providing some benefit [against CAD], how far out they are from their events, potentially what their bleeding risk is.”

On the other hand, the practice of giving aspirin to patients who do not have CAD is more counterintuitive, he added, since it is unclear what the aspirin is meant to treat. “Our best guess is that these patients are thought by their physicians to be at significant risk for cardiovascular disease,” Dr. Steinberg said.

But overall, he said, the concept of “less is more” is gaining traction.

In an accompanying editorial, Carlo Patrono, MD, and Felicita Andreotti, MD, PhD, both of the Catholic University School of Medicine (Rome, Italy), emphasize that the landscape is evolving.

Several new oral anticoagulants (dabigatran, apixaban, and rivaroxaban) are available, as are new P2Y12 inhibitors (prasugrel and ticagrelor), they note. Moreover, recent DES offer lower risk of stent thrombosis, and bioresorbable stents are on the horizon. There also is “increasing awareness of potential nonvascular health benefits (eg, prevention of colorectal cancer) of long-term aspirin therapy,” they write.

Such factors may lead to broader assessment of each patient’s ischemic and bleeding risks, resulting in more personalized antithrombotic therapy, Drs. Patrono and Andreotti propose.

Study Details

Patients on dual therapy consisting of both an oral anticoagulant and aspirin were slightly younger and more likely to be male but they also tended to have more comorbidities. They also were more likely than patients on oral anticoagulation alone to have new-onset or paroxysmal A-fib vs. longstanding persistent A-fib. CHADS₂ scores indicated higher stroke risk among patients on dual therapy, though ATRIA bleeding risk scores and prior GI bleeding rates were similar between the 2 groups.

Note: Coauthor Michael D. Ezekowitz, MD, PhD, of Thomas Jefferson Medical College (Philadelphia, PA), is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Sources:
1. Steinberg BA, Kim S, Piccini JP, et al. Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: Insights from the ORBIT-AF registry. Circulation. 2013;Epub ahead of print.

2. Patrono C, Andreotti F. Antithrombotic therapy for patients with atrial fibrillation and atherothrombotic vascular disease: Striking the right balance between efficacy and safety. Circulation. 2013;Epub ahead of print.

 

 

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