Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation

  • STATUS
    Recruiting
  • End date
    Dec 23, 2022
  • participants needed
    4000
  • sponsor
    Population Health Research Institute
Updated on 23 September 2020
diabetes
aspirin
stroke
atrial fibrillation
ischemic stroke
vascular disease
apixaban
atrial flutter
embolism

Summary

This study aims to determine if treatment with apixaban, compared with aspirin, will reduce the risk of ischemic stroke and systemic embolism in patients with device-detected sub-clinical atrial fibrillation and additional risk factors for stroke.

Description

Device-detected sub-clinical atrial fibrillation (SCAF) is a new disorder that has been recognized since the availability of implantable devices capable of long term continuous heart rhythm monitoring. It is characterized by one or more runs of rapid atrial arrhythmia detected by the device without symptoms and without any clinical atrial fibrillation (AF) detected by the usual methods, (i.e. electrocardiogram, Holter monitor, etc.). In the ASSERT trial, SCAF was detected by a pacemaker or implantable cardioverter defibrillator (ICD) in nearly 40% of patients during 2 and a half years of follow up. The presence of SCAF increased stroke risk by 2.5-fold (1). The risk of stroke or systemic embolism among patients with SCAF and a CHADS2 score 4 was 2.75% per year. Oral anticoagulation is effective and safe for stroke prevention in patients with clinical atrial fibrillation, but it is unknown if the same risk benefit ratio exists for anticoagulation therapy in patients with SCAF (2;3). SCAF differs from clinical AF in being of shorter duration, being asymptomatic, and often have a more regular rhythm in the right atrium where it is typically detected. Data ASSERT suggest that the increase in stroke risk with SCAF may be less than the increase with clinical AF. Therefore opinion leaders have written that the role of oral anticoagulation for the treatment of SCAF is uncertain and that randomized trials of anticoagulation are needed (4;5). Recent surveys of pacemaker clinic practice indicate that only 25% of patients with SCAF are treated with oral anticoagulation (6;7). Thus there is clinical equipoise for a trial of oral anticoagulation compared to aspirin in higher risk patients with SCAF.

Apixaban is a Factor Xa inhibitor that is an effective and safe anticoagulant. It has been shown to have an excellent risk benefit profile for stroke prevention in clinical AF (14, 15). It is highly suitable to test if oral anticoagulation therapy will reduce the risk of stroke or systemic embolism in SCAF.

Patients will be randomized double-blind to receive apixaban or aspirin. Apixaban dose will be 5 mg twice daily (2.5 mg twice daily if 2 or more of: age > 80, weight 60 kg or serum creatinine 133 mmol/L). Those assigned to aspirin will receive a dose of 81 mg daily. The study will be event driven and will continue until 248 patients have experienced a primary outcome event.

Details
Treatment Aspirin, Apixaban
Clinical Study IdentifierNCT01938248
SponsorPopulation Health Research Institute
Last Modified on23 September 2020

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Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 55 yrs?
Gender: Male or Female
Do you have any of these conditions: Cerebrovascular accident or Arrhythmia or Dysrhythmia or Atrial Fibrillation or Stroke or Atrial Fibrillation (Pediatric)?
Permanent pacemaker or defibrillator (with or without resynchronization) or insertable cardiac monitor capable of detecting SCAF
At least one episode of SCAF 6 minutes in duration but no single episode > 24 hours in duration at any time prior to enrollment. Any atrial high rate episode with average > 175 beats/min will be considered as SCAF. No distinction will be made between atrial fibrillation and atrial flutter. SCAF requires electrogram confirmation (at least one episode) unless 6 hours in duration
Age 55 years
Risk Factor(s) for Stroke
Previous stroke, TIA or systemic arterial embolism OR Age at least 75 OR Age
-74 with at least 2 other risk factors OR Age 55-64 with at least 3 other
risk factors
Other risk factors are
hypertension
CHF
diabetes
vascular disease (i.e. CAD, PAD or Aortic Plaque)
female

Exclusion Criteria

Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry, Holter) lasting 6 minutes, with or without clinical symptoms
Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other condition requiring treatment with an anticoagulant
Contra-indication to apixaban or aspirin
Allergy to aspirin or apixaban
Severe renal insufficiency (creatinine clearance must be calculated in all patients; any patient with either a serum creatinine > 2.5 mg/dL [221 mol/L] or a calculated creatinine clearance < 25 ml/min is excluded)
Serious bleeding in the last 6 months or at high risk of bleeding (this includes, but is not limited to: prior intracranial hemorrhage, active peptic ulcer disease, platelet count < 50,000/mm3 or hemoglobin < 10 g/dL, recent stroke within past 10 days, documented hemorrhagic tendencies or blood dyscrasias)
Moderate to severe hepatic impairment
Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors)
Meets criteria for requiring lower dose of apixaban AND also has ongoing need for strong inhibitors of CYP 3A4 or P-glycoprotein (e.g., ketoconazole, itraconazole, ritonavir or clarithromycin)
Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)
Received an investigational drug in the past 30 days
Participants considered by the investigator to be unsuitable for the study for any of the following reasons
Not agreeable for treatment with either aspirin or apixaban or anticipated to have poor compliance on study drug treatment
Unwilling to attend study follow-up visits
Life expectancy less than the expected duration of the trial2 years due to concomitant disease
Women who are pregnant, breast-feeding or of child-bearing potential without an acceptable form of contraception in place (sterilization, hormonal contraceptives, intrauterine device, barrier methods or abstinence)
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