Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation - ARTESIA

Sep 11, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Canadian Institutes of Health Research
Date Presented:
11/12/2023
Date Published:
09/04/2024
Date Updated:
09/11/2024
Original Posted Date:
11/11/2023
References

Contribution To Literature:

Highlighted text has been updated as of September 11, 2024.

The ARTESIA trial showed that anticoagulation reduces adverse events compared with aspirin among patients with subclinical AF.

Description:

The goal of the trial was to evaluate apixaban compared with aspirin among patients with subclinical atrial fibrillation (AF).

Study Design

  • Randomized
  • Parallel
  • Blinded

Patients with subclinical AF and increased risk for stroke were randomized to apixaban 5 mg twice daily (n = 2,015) vs. aspirin 81 mg daily (n = 1,997).

  • Total number of enrollees: 4,012
  • Duration of follow-up: mean 3.5 years
  • Mean patient age: 76.8 years
  • Percentage female: 36%
  • Percentage with diabetes: 29%

Inclusion criteria:

  • Subclinical AF (detected by pacemaker, defibrillator, or cardiac monitor)
  • At least one episode of AF that lasted between 6 minutes and 24 hours
  • CHA2DS2-VASc score ≥3

Exclusion criteria:

  • Clinical AF
  • Ongoing indication for oral anticoagulation
  • History of major bleeding in the previous 6 months
  • Creatinine clearance <25 mL/min

Other salient features/characteristics:

  • Mean CHA2DS2-VASc score = 3.9
  • CHA2DS2-VASc score ≥4, 60.7%

Number of episodes of AF:

  • 0, 17.7%
  • 1 to 5, 63.7%
  • 6 to 50, 16.5%
  • >50, 4.1%

Longest episode of AF:

  • No episodes, 15.8%
  • <6 minutes, 2.1%
  • 6 minutes to <1 hour, 25.8%
  • 1 to <6 hours, 35.5%
  • 6 to <12 hours, 13.8%
  • 12 to 24 hours, 7.1%

Principal Findings:

The primary efficacy outcome, stroke or systemic embolism, was: 0.78%/person-year in the apixaban group vs. 1.24%/person-year in the aspirin group (p = 0.007).

The primary safety outcome, major bleeding, was: 1.53%/person-year in the apixaban group vs. 1.12%/person-year in the aspirin group (p = 0.04).

Treatment differences according to CHA2DS2-VASc:

Stroke or systemic embolism among those with:

  • CHA2DS2-VASc <4, absolute risk reduction for apixaban vs. aspirin: -0.04 (95% CI -1.94 to 1.85)
  • CHA2DS2-VASc = 4, absolute risk reduction for apixaban vs. aspirin: -2.25 (95% CI -4.19 to -0.31)
  • CHA2DS2-VASc >4, absolute risk reduction for apixaban vs. aspirin: -3.95 (95% CI -6.72 to -1.19) (p for interaction = 0.06)

Major bleeding among those with:

  • CHA2DS2-VASc <4, absolute risk reduction for apixaban vs. aspirin: 1.28 (95% CI -0.98 to 3.55)
  • CHA2DS2-VASc = 4, absolute risk reduction for apixaban vs. aspirin: 0.05 (95% CI -2.03 to 2.14)
  • CHA2DS2-VASc >4, absolute risk reduction for apixaban vs. aspirin: 1.70 (95% CI -1.25 to 4.66) (p for interaction = 0.6)

Frequency and duration of AF and stroke risk:

  • Stroke or systemic embolism according to frequency: 1.1%/patient-year for 1-5 episodes vs. 1.2%/patient-year for ≥6 episodes (adjusted hazard ratio 0.89 [95% CI 0.59–1.34]). The frequency of subclinical AF did not modify the reduction in stroke or systemic embolism with apixaban (p for interaction = 0.1).
  • Stroke or systemic embolism according to duration: <1 hour, 1.0%/patient-year; 1–6 hours, 1.2%/patient-year; >6 hours, 1.0%/patient/year (adjusted hazard ratio 1.02 [95% CI 0.63–1.66]). The duration of subclinical AF did not modify the reduction in stroke or systemic embolism with apixaban (p for trend = 0.1).

Interpretation:

Among patients with subclinical AF and increased risk for stroke, apixaban reduced the risk of stroke or systemic embolism compared with aspirin. However, apixaban was associated with an increased risk of major bleeding compared with aspirin. Subclinical AF is associated with a 2.5-fold increased risk of stroke or systemic embolism; however, until this trial, it was unknown if anticoagulation therapy would reduce stroke risk. Neither the frequency nor duration of subclinical AF modified the association between subclinical AF and risk of stroke or systemic embolism.

The reduction in stroke or systemic embolism with apixaban needs to be balanced against the increased risk of major bleeding compared with aspirin. Among those with elevated CHA2DS2-VASc score, apixaban vs. aspirin was associated with a significant reduction in stroke or systemic embolism. Among those with low CHA2DS2-VASc score, apixaban vs. aspirin was not associated with a significant reduction in stroke or systemic embolism. These results directly apply to patients with subclinical AF detected by an implantable cardiac device with increased risk for stroke.

References:

McIntyre WF, Benz AP, Healey JS, et al. Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial. Circulation 2024;Sep 4:[Epub ahead of print].

Lopes RD, Granger CB, Wojdyla DM, et al. Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA. J Am Coll Cardiol 2024;84:354-64.

Editorial Comment: Shah SJ. Anticoagulants in Subclinical Atrial Fibrillation: Beginning to Define the Treatment Paradigm. J Am Coll Cardiol 2024;84:365-7.

Healey JS, Lopes RD, Granger CB, et al., on behalf of the ARTESIA Investigators. Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation. N Engl J Med 2024;390:107-17.

Svennberg E. Editorial: What Lies beneath the Surface — Treatment of Subclinical Atrial Fibrillation. N Engl J Med 2024;390:175-7.

Presented by Dr. Jeff Healey at the American Heart Association Scientific Sessions, Philadelphia, PA, November 12, 2023.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Vascular Medicine

Keywords: AHA23, AHA Annual Scientific Sessions, Anticoagulants, Atrial Fibrillation, Embolism, Stroke


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