CE / CME
Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit
Nurses: 1.00 Nursing contact hour
Pharmacists: 1.00 contact hour (0.1 CEUs)
Physicians: maximum of 1.00 AMA PRA Category 1 Credit™
Released: June 26, 2024
Expiration: June 25, 2025
ASSERT: Device-Detected Atrial Fibrillation
The increasing use of fitness devices with irregular rhythms alerts is giving us new information regarding the prevalence of subclinical atrial fibrillation. This slide depicts data from the ASSERT trial, which demonstrated that subclinical atrial fibrillation is common in patients with pacemakers without earlier known atrial fibrillation and is associated with increased risk of ischemic stroke or systemic embolism.25
ASSERT included 2580 patients older than 65 years of age with hypertension and without an earlier diagnosis of atrial fibrillation who received a pacemaker or implantable cardioverter defibrillator. The effect of subclinical atrial fibrillation duration on subsequent risk of ischemic stroke or embolism was evaluated.
Subclinical atrial fibrillation that lasted longer than 24 hours was associated with a significant increased risk of subsequent stroke or systemic embolism. The risk of ischemic stroke or systemic embolism in patients with subclinical atrial fibrillation lasting between 6 minutes and 24 hours was not significantly different from patients without subclinical atrial fibrillation.
ASSERT: Absolute Risk of Stroke in Patients With Subclinical and Clinical Atrial Fibrillation
Although subclinical atrial fibrillation is not as prognostically important as clinical atrial fibrillation, there still is clearly increased risk of stroke compared with those without atrial fibrillation.
This is a subanalysis of ASSERT that shows patients at 3 risk levels for stroke based on CHA2DS2-VASc scores. Within each, one can see increasing risk for stroke with no atrial fibrillation, subclinical atrial fibrillation, and finally, clinical atrial fibrillation (Healey, personal communication).
Randomized Clinical Trials of Patients With Device-Detected Atrial Fibrillation
Two recent trials that have provided evidence about management of patients with subclinical atrial fibrillation.
The NOAH–AFNET 6 trial tested whether oral anticoagulation with edoxaban is superior in preventing stroke or cardiovascular death compared with aspirin or no antithrombotic therapy. It was a double-blind, double-dummy, randomized trial involving patients aged 65 years or older who had atrial high-rate events lasting for ≥6 minutes and who had 1 or more additional risk factor for stroke.
Patients were randomly assigned to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding.26
NOAH-AFNET 6: Anticoagulation With Edoxaban in Patients With Atrial High-Rate Episodes
NOAH-AFNET 6 showed a small nonsignificant reduction in stroke, systemic embolism, and cardiovascular death; the overall ischemic stroke rate among those in the trial was very low, at 1% per year.26 There was an increased risk of bleeding with edoxaban. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an assessment of futility for the efficacy of edoxaban.
The conclusions from NOAH-AFNET 6 were that anticoagulation with edoxaban did not significantly reduce major endpoints in patients with subclinical atrial fibrillation.
ARTESiA: Apixaban for Stroke Prevention in Patients With Subclinical Atrial Fibrillation
In ARTESiA, patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin 81 mg daily.27 The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting longer than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome was stroke or systemic embolism.
ARTESiA: Anticoagulation With Apixaban or Aspirin in Patients With Device-Detected Atrial Fibrillation
ARTESiA was a larger trial than NOAH-AFNET 6 with 4012 enrolled patients and it demonstrated a significant 37% reduction in risk of ischemic stroke with apixaban but also showed an increased risk of bleeding with apixaban vs aspirin.27 As with NOAH-AFNET 6, there was a low (1.2%) per year annual risk of stroke.
The debate continues on how best to treat these patients, but these results seem compelling.
ARTESiA: Reduction of Stroke With Apixaban or Aspirin in Patients With Device-Detected Atrial Fibrillation
When the investigators in ARTESiA looked more closely at stroke reduction in this trial, they noticed that for more disabling strokes—modified Rankin score 3-6—there was even a greater reduction of 51%.27
ARTESiA: Bleeding With Apixaban or Aspirin in Patients With Device-Detected Atrial Fibrillation
Major bleeding events were significantly increased with apixaban, but fatal bleeding and intracranial hemorrhage were lower with apixaban vs aspirin in the ARTESiA trial.27
Meta-analysis of NOAH-AFNET 6 and ARTESiA for All-Cause Stroke or Systemic Embolism in Patients With Device-Detected Atrial Fibrillation
To help decide the issue of whether anticoagulation is beneficial for patients with device-detected atrial fibrillation, McIntyre and colleagues28 conducted a meta-analysis of NOAH-AFNET 6 and ARTESiA. Their results showed a 32% relative risk (RR) reduction over approximately 2-4 years in risk of stroke (RR: 0.68; 95% CI: 0.50-0.92). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR: 0.85; 95% CI: 0.73-0.99).
2023 ACC/AHA Guidelines: Subclinical Atrial Fibrillation
The expert panel made the following recommendation for anticoagulation of patients with subclinical atrial fibrillation based on risk per year: If patients have ≥2% per year risk of stroke, then anticoagulation is recommended. If the risk is 1% to 2% per year, then anticoagulation should be considered.1
ARTESiA Results by Subgroup
Who are these patients with subclinical atrial fibrillation who have ≥2% per year risk of stroke? Preliminary unpublished data from the ARTESiA trial showed that 27% of patients receiving apixaban had CHA2DS2-VASc score >4 and >2% annual risk of stroke on aspirin. In this group, risk of stroke was reduced by 50% with apixaban. These patients would be candidates for DOACs.
In ARTESiA, among patients with previous stroke, approximately 9% had a 3% annual risk of stroke on aspirin; this group experienced 60% reduction in risk of stroke. This would be an additional group for whom one should strongly consider anticoagulation for those patients with subclinical atrial fibrillation.
Anticoagulation for Patients With Device-Detected Irregular Rhythm and No Clinical Atrial Fibrillation
This is a proposed approach for how to consider patients with no clinical signs of atrial fibrillation who come in who have an irregular rhythm alert on their watch or fitness device. A first consideration should be whether the patient has risk factors for stroke. The first question is whether they have risk factors for stroke. Do they have a CHA2DS2-VASc score ≥2? If not, focused evaluation may be recommended. These patients most likely will not need any long-term monitoring or additional evaluation but assessment in the future for any signs of clinical atrial fibrillation.
On the other hand, patients who do have additional risk factors for stroke should undergo additional rhythm monitoring, perhaps over 2-4 weeks, to assess their burden of atrial fibrillation. They should also undergo a more careful evaluation, including a 12-lead electrocardiogram, echocardiogram, thyroid evaluation, and perhaps NT-proBNP measurement. If on the additional monitoring, atrial fibrillation is detected for ≥6 minutes, and if they have these risk factors from the clinical trials of device-detected atrial fibrillation (episodes lasting >24 hours, CHA2DS2-VASc >4, increased left atrial size, NT-proBNP increased), then they should be treated with a DOAC. If the risk factors are absent or inconclusive, ongoing surveillance and longer-term monitoring would be prudent.
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