ORBIT-AF

Published

Steinberg BA, et al. "Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry". Circulation. 2013. 128(7):721-8.
PubMed • Full text • PDF

Clinical Question

In patients with atrial fibrillation, are there more risks associated with the use of aspirin plus oral anticoagulation therapy versus anticoagulation therapy alone?

Bottom Line

In patients with atrial fibrillation (AF) treated with oral anticoagulation (OAC), this retrospective review demonstrated increased bleeding and hospitalization rates with the concomitant use of aspirin versus OAC alone.

Major Points

AF was first identified as a risk factor for stroke in a 1978 Framingham study publication. The 1991 SPAF study demonstrated that AF was an independent risk factor for stroke, and that warfarin was superior to aspirin for stroke prevention. Many patients with AF are treated with aspirin without a compelling indication or fail to meet the USPSTF recommendation for aspirin to reduce the risk of myocardial infarction or stroke. There have been few studies to determine if patients are subjected to increased bleeding risks when treated with aspirin plus oral anticoagulation therapy as opposed to oral anticoagulation therapy alone for the prophylaxis of thromboembolic events.

The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) was an observational study that followed 7,347 patients with AF and on OAC enrolled in the ORBIT registry. Most patients were taking warfarin, but a small proportion were taking dabigatran (6.9%) for thromboembolic prophylaxis. Patients were stratified according to concomitant use of aspirin and two groups were studied: OAC plus aspirin, or OAC alone. Primary outcomes were bleeding, hospitalization, CV events, and mortality. At 6 months, there were significantly more bleeding events and hospitalizations with combination therapy compared to OAC alone. It appeared that patients with a history of CAD may see more benefits than risks with the use of the combination.

Guidelines

ACCF/AHA/ESC Guidelines (2011, adapted)

• Low dose aspirin may be added to anticoagulation to prevent ischemic events in patients with class IIb AF (previous PCI or revascularization), although this has not been evaluated thoroughly and may increase bleeding
• Note: the 2014 AF guidelines do not comment on aspirin+oral anticoagulants.

European Society of Cardiology (2010, adapted)

• Recommendations based on risk factors for stroke and thromboembolism
• OAC for patients with CHADS₂ score ≥2

American College of Chest Physicians (2012, adapted)

• For patients with AF and stable coronary artery disease (e.g., no acute coronary syndrome within the previous year) and who choose oral anticoagulation, the expert panel suggests adjusted-dose VKA therapy alone rather than the combination of adjusted-dose VKA therapy and aspirin (Grade 2C).

Design

• Retrospective review of prospective, multicenter, outpatient registry
• N=7,347
  • OAC (n=4,804)
  • OAC plus aspirin (2,543)
• Setting: 174 US sites
• Follow-up: 6 months
• Primary outcomes: bleeding, hospitalization, CV events, and mortality

Population

Inclusion Criteria

• Age ≥ 18 years
• Atrial fibrillation on EKG

Exclusion Criteria

• Anticipated life expectancy <6 months
• Atrial flutter only
• Patients not taking oral anticoagulant
• Patients taking antiplatelet therapies other than ASA
• Transient AF secondary to a reversible condition
• Current enrollment in a randomized clinical trial of antithrombotic therapy for AF

Baseline Characteristics

Comparisons are OAC vs. OAC plus aspirin.

• Median age: 76 vs. 75
• Female: 47% vs. 34%
• Race
  • White: 88% vs. 92%
  • Black: 5.0% vs. 4.3%
  • Hispanic: 5.8% vs. 2.1
• Medical History
  • Smoking: 45% vs. 54%
  • Hypertension: 83% vs. 87%
  • Hyperlipidemia: 69% vs. 79%
  • Diabetes mellitus: 28% vs. 35%
  • Obstructive sleep apnea: 17% vs. 21%
  • Heart failure: 31% vs. 39%
  • GI bleeding: 7.8%
  • Anemia: 16% vs. 19%
  • COPD: 15% vs. 18%
• Hemoglobin: 13.6 vs. 13.5 g/dL [136 vs. 135 g/L]
• Calculated creatinine clearance: 69 vs. 72 mL/min/1.73m2
• Mean LVEF: 55.2% vs. 52.6%

Interventions

• This was a non-interventional study
• ORBIT registry enrolled 10,126 patients
• 7,347 patients met the inclusion/exclusion criteria for ORBIT-AF
• Patients stratified according to OAC alone or OAC plus aspirin

Outcomes

Comparisons are OAC vs. OAC plus aspirin at 6 months of follow-up.

Primary Outcome

Major bleeding

1.8% vs. 3.0% (HR 1.53; P=0.0006; NNH=83)

Hospitalization for any cause

19% vs. 23% (HR 1.08; P=0.06)

Mortality

1.9% vs. 2.6% (HR 1.26; P=0.08)

Myocardial infarction

0.38% vs. 0.48%

Coronary revascularization

0.66% vs. 1.35%

Ischemic stroke

0.42% vs. 0.65%

TIA

0.17% vs. 0.13%

Secondary Outcomes

Nuisance bleeding

10% vs. 11% (HR 1.09; P=0.18)

Bleeding hospitalization

1.6% vs. 2.6% (HR 1.52; P=0.002; NNH=100)

Cardiovascular hospitalization

10.9% vs. 13.3% (HR 1.08; P=0.14)

Other causes of hospitalization

8.6% vs. 9.6% (HR 0.98; P=0.72)

Subgroup Analysis

Populations in which aspirin plus oral anticoagulation may be preferred:

• History of CAD (OR 2.23; 95% CI 1.82-2.73)
• Previous maze procedure (OR 1.56; 95% CI 1.05-2.32)
• Any drug eluting stent (OR 1.53; 95% CI 1.17-2.01)
• Previous stroke or TIA (OR 1.45; 95% CI 1.25-1.67)

Criticisms

• Results were only indicative of patients that had completed follow-up; 11% of patients were lost to follow-up.
• The non-exposed cohort was drawn from the same communities and settings as the exposed cohort
• Follow-up time was long enough for harmful and some beneficial outcomes to occur
• The quality of this study was assessed using the Newcastle-Ottawa Scale, in which the study earned 7 out of 9 "stars"

Funding

• Sponsored by Janssen Scientific Affairs, LLC, Raritan, NJ
• Dr. Steinberg funded by the National Institutes of Health T-32 training grant 5 T32 HL 7101-37