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

Recruiting

Phase 4 Results N/A

Update History

31 May '17
The gender criteria for eligibility was updated to "All."
A location was updated in Larkspur.
New
The overall status was updated to "Terminated" at Cardiovascular Associates of Marin and San Francisco Medical.
A location was updated in Sudbury.
New
The overall status was updated to "Terminated" at Health Sciences North.
7 Oct '16
The minimum age criteria for eligibility was updated to "55 Years."
The eligibility criteria were updated.
New
Inclusion Criteria: 1. Permanent pacemaker or defibrillator (with or without resynchronization) or insertable cardiac monitor capable of detecting SCAF 2. 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. 3. Age ≥ 55 years 4. Risk Factor(s) for Stroke: Previous stroke, TIA or systemic arterial embolism OR Age at least 75 OR Age 65-74 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: 1. Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry, Holter) lasting ≥ 6 minutes, with or without clinical symptoms 2. Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other condition requiring treatment with an anticoagulant 3. Contra-indication to apixaban or aspirin: 1. Allergy to aspirin or apixaban 2. Severe renal insufficiency (creatinine clearance must be calculated in all patients; any patient with either a serum creatinine > 2.5 mg/dL [221 µmol/L] or a calculated creatinine clearance < 25 ml/min is excluded) 3. 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) 4. Moderate to severe hepatic impairment 5. Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors) 6. 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) 7. Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) 4. Received an investigational drug in the past 30 days 5. Participants considered by the investigator to be unsuitable for the study for any of the following reasons: 1. Not agreeable for treatment with either aspirin or apixaban or anticipated to have poor compliance on study drug treatment 2. Unwilling to attend study follow-up visits 3. Life expectancy less than the expected duration of the trial2 years due to concomitant disease 6. 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)
Old
Inclusion Criteria: 1. Permanent pacemaker or defibrillator (with or without resynchronization) or insertable cardiac monitor capable of detecting SCAF 2. At least one episode of SCAF ≥ 6 minutes in duration (Atrial rate > 175/min if an atrial lead is present), but no single episode > 24 hours in duration. SCAF requires electrogram confirmation (at least one episode) unless ≥ 6 hours in duration 3. Age > 18 years 4. CHA2DS2-VASc score of ≥ 4 Exclusion Criteria: 1. Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry, Holter) lasting ≥ 6 minutes, with or without clinical symptoms 2. Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other condition requiring treatment with an anticoagulant 3. Contra-indication to apixaban or aspirin: 1. Allergy to aspirin or apixaban 2. Severe renal insufficiency (creatinine clearance must be calculated in all patients; any patient with either a serum creatinine > 2.5 mg/dL [221 µmol/L] or a calculated creatinine clearance < 25 ml/min is excluded) 3. 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) 4. Moderate to severe hepatic impairment 5. Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors) 6. 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) 7. Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) 4. Received an investigational drug in the past 30 days 5. Participants considered by the investigator to be unsuitable for the study for any of the following reasons: 1. Not agreeable for treatment with either aspirin or apixaban or anticipated to have poor compliance on study drug treatment 2. Unwilling to attend study follow-up visits 3. Life expectancy less than the expected duration of the trial2 years due to concomitant disease 6. 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)
26 Sep '15
The description was updated.
New
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.
Old
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.
The eligibility criteria were updated.
New
Inclusion Criteria: 1. Permanent pacemaker or defibrillator (with or without resynchronization) or insertable cardiac monitor capable of detecting SCAF 2. At least one episode of SCAF ≥ 6 minutes in duration (Atrial rate > 175/min if an atrial lead is present), but no single episode > 24 hours in duration. SCAF requires electrogram confirmation (at least one episode) unless ≥ 6 hours in duration 3. Age > 18 years 4. CHA2DS2-VASc score of ≥ 4 Exclusion Criteria: 1. Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry, Holter) lasting ≥ 6 minutes, with or without clinical symptoms 2. Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other condition requiring treatment with an anticoagulant 3. Contra-indication to apixaban or aspirin: 1. Allergy to aspirin or apixaban 2. Severe renal insufficiency (creatinine clearance must be calculated in all patients; any patient with either a serum creatinine > 2.5 mg/dL [221 µmol/L] or a calculated creatinine clearance < 25 ml/min is excluded) 3. 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) 4. Moderate to severe hepatic impairment 5. Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors) 6. 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) 7. Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) 4. Received an investigational drug in the past 30 days 5. Participants considered by the investigator to be unsuitable for the study for any of the following reasons: 1. Not agreeable for treatment with either aspirin or apixaban or anticipated to have poor compliance on study drug treatment 2. Unwilling to attend study follow-up visits 3. Life expectancy less than the expected duration of the trial2 years due to concomitant disease 6. 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)
Old
Inclusion Criteria: 1. Permanent pacemaker or defibrillator (with or without resynchronization) or insertable cardiac monitor capable of detecting SCAF 2. At least one episode of SCAF ≥ 6 minutes in duration (Atrial rate > 175/min if an atrial lead is present), but no single episode > 24 hours in duration. SCAF requires electrogram confirmation (at least one episode) unless ≥ 6 hours in duration 3. Age > 18 years 4. CHA2DS2-VASc score of ≥ 4 Exclusion Criteria: 1. Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry, Holter) lasting ≥ 6 minutes, with or without clinical symptoms 2. Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other condition requiring treatment with an anticoagulant 3. Contra-indication to apixaban or aspirin: 1. Allergy to aspirin or apixaban 2. Severe renal insufficiency (creatinine clearance must be calculated in all patients; any patient with either a serum creatinine > 2.5 mg/dL [221 µmol/L] or a calculated creatinine clearance < 25 ml/min is excluded) 3. 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) 4. Moderate to severe hepatic impairment 5. Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors) 6. 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) 7. Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) 4. Received an investigational drug in the past 30 days 5. Participants considered by the investigator to be unsuitable for the study for any of the following reasons: 1. Not agreeable for treatment with either aspirin or apixaban or anticipated to have poor compliance on study drug treatment 2. Unwilling to attend study follow-up visits 3. Life expectancy less than the expected duration of the trial2 years due to concomitant disease 6. 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)
7 Nov '14
Trial name was updated.
New
Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation
The Summary of Purpose was updated.
New
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.
Old
This study aims to determine if treatment with apixaban, compared with aspirin, will reduce the risk of ischemic stroke and systemic embolism in pacemaker patients with sub-clinical atrial fibrillation and additional risk factors for stroke.
The description was updated.
New
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.
Old
There are over sixty thousand Canadians with pacemakers or implanted defibrillators. More than 40% of these patients will develop sub-clinical atrial fibrillation (SCAF), which is a short-lasting, typically asymptomatic arrhythmia that would not be detected by means other than a modern, dual-chamber pacemaker. Only 15% of patients with SCAF also have clinical atrial fibrillation (AF) and until recently, the significance of isolated SCAF was debated. However; our group published the ASSERT trial, which demonstrated that in patients with hypertension, but without clinical AF, SCAF ≥ 6 minutes in duration was associated with a 2.5-fold increased risk of stroke; which among patients with CHA2DS2-VASC score > 3 was associated with a stroke risk of 2.75% per year. However; the optimal approach to stroke prevention for patients with SCAF is controversial and oral anticoagulation (OAC) is usually not employed. As OAC can prevent 60-80% of ischemic strokes in patients with clinical AF, it is critical that we determine its roll in patients with SCAF. Many patients with pacemakers and implanted defibrillators are followed semi-annually by cardiologists and nurses in device clinics and many of them have a CHA2DS2-VASC score > 3. They represent a large, high-risk and easily identifiable group of patients who are highly compliant with follow-up. ARTESiA will enroll 3,719 patients with a pacemaker or implanted defibrillator, a CHA2DS2-VASC score > 3 and at least one episode of SCAF ≥ 6 minutes who do not have a history of clinical AF and who do not have a contra-indication to oral anticoagulation. Patients will be randomized to receive either the oral anticoagulant apixaban or aspirin, in a double-blind, double-dummy fashion and will be followed for the primary outcome of ischemic stroke or systemic embolism. ARTESiA will help define the role of OAC in patients with pacemakers and defibrillations who have SCAF; providing clinicians with important guidance for this common problem. However; the implications of ARTESiA go beyond the pacemaker population. New cardiac rhythm monitoring technologies are increasingly being used in clinical practice and suggest a high prevalence of SCAF among older individuals without pacemakers, but with cardiovascular risk factors. The results of ARTESiA will give insights for this much larger and rapidly growing group of patients.
The minimum age criteria for eligibility was updated to "18 Years."
The eligibility criteria were updated.
New
Inclusion Criteria: 1. Permanent pacemaker or defibrillator (with or without resynchronization) or insertable cardiac monitor capable of detecting SCAF 2. At least one episode of SCAF ≥ 6 minutes in duration (Atrial rate > 175/min if an atrial lead is present), but no single episode > 24 hours in duration. SCAF requires electrogram confirmation (at least one episode) unless ≥ 6 hours in duration 3. Age > 18 years 4. CHA2DS2-VASc score of ≥ 4 Exclusion Criteria: 1. Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry, Holter) lasting ≥ 6 minutes, with or without clinical symptoms 2. Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other condition requiring treatment with an anticoagulant 3. Contra-indication to apixaban or aspirin: 1. Allergy to aspirin or apixaban 2. Severe renal insufficiency (creatinine clearance must be calculated in all patients; any patient with either a serum creatinine > 2.5 mg/dL [221 µmol/L] or a calculated creatinine clearance < 25 ml/min is excluded) 3. 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) 4. Moderate to severe hepatic impairment 5. Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors) 6. 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) 7. Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) 4. Received an investigational drug in the past 30 days 5. Participants considered by the investigator to be unsuitable for the study for any of the following reasons: 1. Not agreeable for treatment with either aspirin or apixaban or anticipated to have poor compliance on study drug treatment 2. Unwilling to attend study follow-up visits 3. Life expectancy less than the expected duration of the trial2 years due to concomitant disease 6. 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)
Old
Inclusion Criteria: Patients with a dual-chamber pacemaker or implantable defibrillator with: - At least one SCAF (subclinical atrial fibrillation) ≥ 6 minutes in duration - CHA2DS2-VASc score of > 3 - Not current receiving chronic therapy with an oral anticoagulant Exclusion Criteria: - Clinical AF documented by 12 lead ECG, or by continuous ECG monitoring, with or without clinical symptoms; OR SCAF (pacemaker/ICD-detected) of > 24 hours continuous curation - Mechanical valve prosthesis, deep vein thrombosis or pulmonary embolism or other ongoing indication for oral anticoagulation - eGFR < 25 mL/min - Use of strong inhibitors of CYP-3A4 or P-gp (i.e., clarithromycin, etc.) - Contra-indication to oral anticoagulants or ASA: - Prior intracranial hemorrhage - Platelet count < 50,000 - Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors) - Allergy to ASA - Unwilling to attend study follow-up
13 Sep '13
The description was updated.
New
There are over sixty thousand Canadians with pacemakers or implanted defibrillators. More than 40% of these patients will develop sub-clinical atrial fibrillation (SCAF), which is a short-lasting, typically asymptomatic arrhythmia that would not be detected by means other than a modern, dual-chamber pacemaker. Only 15% of patients with SCAF also have clinical atrial fibrillation (AF) and until recently, the significance of isolated SCAF was debated. However; our group published the ASSERT trial, which demonstrated that in patients with hypertension, but without clinical AF, SCAF ≥ 6 minutes in duration was associated with a 2.5-fold increased risk of stroke; which among patients with CHA2DS2-VASC score > 3 was associated with a stroke risk of 2.75% per year. However; the optimal approach to stroke prevention for patients with SCAF is controversial and oral anticoagulation (OAC) is usually not employed. As OAC can prevent 60-80% of ischemic strokes in patients with clinical AF, it is critical that we determine its roll in patients with SCAF. Many patients with pacemakers and implanted defibrillators are followed semi-annually by cardiologists and nurses in device clinics and many of them have a CHA2DS2-VASC score > 3. They represent a large, high-risk and easily identifiable group of patients who are highly compliant with follow-up. ARTESiA will enroll 3,719 patients with a pacemaker or implanted defibrillator, a CHA2DS2-VASC score > 3 and at least one episode of SCAF ≥ 6 minutes who do not have a history of clinical AF and who do not have a contra-indication to oral anticoagulation. Patients will be randomized to receive either the oral anticoagulant apixaban or aspirin, in a double-blind, double-dummy fashion and will be followed for the primary outcome of ischemic stroke or systemic embolism. ARTESiA will help define the role of OAC in patients with pacemakers and defibrillations who have SCAF; providing clinicians with important guidance for this common problem. However; the implications of ARTESiA go beyond the pacemaker population. New cardiac rhythm monitoring technologies are increasingly being used in clinical practice and suggest a high prevalence of SCAF among older individuals without pacemakers, but with cardiovascular risk factors. The results of ARTESiA will give insights for this much larger and rapidly growing group of patients.
Old
There are over sixty thousand Canadians with pacemakers or implanted defibrillators. More than 40% of these patients will develop sub-clinical atrial fibrillation (SCAF), which is a short-lasting, typically asymptomatic arrhythmia that would not be detected by means other than a modern, dual-chamber pacemaker. Only 15% of patients with SCAF also have clinical atrial fibrillation (AF) and until recently, the significance of isolated SCAF was debated. However; our group published the ASSERT trial, which demonstrated that in patients with hypertension, but without clinical AF, SCAF ≥ 6 minutes in duration was associated with a 2.5-fold increased risk of stroke; which among patients with CHA2DS2-VASC score > 3 was associated with a stroke risk of 2.75% per year. However; the optimal approach to stroke prevention for patients with SCAF is controversial and oral anticoagulation (OAC) is usually not employed. As OAC can prevent 60-80% of ischemic strokes in patients with clinical AF, it is critical that we determine its roll in patients with SCAF. Most Canadian patients with pacemakers and implanted defibrillators are followed semi-annually by cardiologists and nurses in 30-35 large device clinics and 63% of them have a CHA2DS2-VASC score > 3. They represent a large, high-risk and easily identifiable group of patients who are highly compliant with follow-up. ARTESiA will enroll 3,719 patients with a pacemaker or implanted defibrillator, a CHA2DS2-VASC score > 3 and at least one episode of SCAF ≥ 6 minutes who do not have a history of clinical AF and who do not have a contra-indication to oral anticoagulation. Patients will be randomized to receive either the oral anticoagulant apixaban or aspirin, in a double-blind, double-dummy fashion and will be followed for the primary outcome of ischemic stroke or systemic embolism. We are seeking CIHR funding for a vanguard phase, which would enroll 300 patients from Canada and three European countries; with a goal of demonstrating an adequate recruitment rate and compliance with therapy. ARTESiA will help define the role of OAC in patients with pacemakers and defibrillations who have SCAF; providing clinicians with important guidance for this common problem. If apixaban therapy reduced stroke by 30- 50%, then the results of ARTESiA could be quickly disseminated to Canadian pacemaker clinics, resulting in the treatment of nearly 15,000 at-risk Canadian patients and the prevention of more than 1000 strokes within 6 years. However; the implications of ARTESiA go beyond the pacemaker population. New cardiac rhythm monitoring technologies are increasingly being used in clinical practice and suggest a high prevalence of SCAF among older individuals without pacemakers, but with cardiovascular risk factors. The results of ARTESiA will give insights for this much larger and rapidly growing group of patients.