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Table 4

From: A meta-epidemiological study of subgroup analyses in cochrane systematic reviews of atrial fibrillation

Author (year)

Title

Objectives

Studies included

Trials (n)

Patients (n)

Primary outcomes

Types of participants

Types of interventions

Huffman et al. [33]

Concomitant atrial fibrillation surgery for people undergoing cardiac surgery

To assess the effects of concomitant AF surgery among people with AF who are undergoing cardiac surgery.

RCTs evaluating the effect of any concomitant AF surgery compared with no AF surgery

22

1899

All-cause mortality, freedom from AF, flutter, or tachycardia. Procedural safety (adverse events)

Adults with pre-operative AF, undergoing cardiac surgery for another indication

Any concomitant AF surgery

Aguilar et al. [26]

Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular AF and no history of stroke or TIA

To characterize relative effect of long-term OAC treatment compared with antiplatelet therapy on major vascular events in patients with non-valvular AF and no history of stroke/TIA.

RCTs in which long-term adjusted-dose OAC was compared with antiplatelet therapy in patients with chronic non-valvular AF.

8

9598

All strokes (ischemic and hemorrhagic)

Non-valvular AF patients, most without previous stroke or TIA

Oral anticoagulation by vitamin K antagonists

Aguilar and Hart [24]

Oral anticoagulants for preventing stroke in patients with non-valvular AF and no previous history of stroke or TIA

To characterize the efficacy and safety of OAC for the primary prevention of stroke in patients with chronic AF.

RCTs comparing OACs with control in patients with chronic non-valvular atrial fibrillation and no history of TIA/stroke.

5

2313

All strokes (ischemic and hemorrhagic)

Non-valvular AF; most without previous stroke or TIA

Oral anticoagulants for preventing stroke in patients with non-valvular AF

Aguilar and Hart [25]

Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or TIA

To characterize the effect of long-term antiplatelet on major vascular events in patients with non-valvular AF and no history of stroke or TIA.

RCTs in which long-term antiplatelet was compared to placebo/control in patients with chronic non-valvular AF.

3

1965

All strokes (ischemic and hemorrhagic)

Non-valvular AF without previous stroke or TIA

Aspirin or other specific platelet anti-aggregants given in any dose, formulation, combination, or frequency were considered.

Saxena and Koudstaal [27]

Anticoagulants for preventing stroke in patients with non-rheumatic atrial fibrillation and a history of stroke or TIA

To determine the value of anticoagulant treatment for the long-term prevention of recurrent vascular events in patients with non-rheumatic AF and previous TIA or minor ischaemic stroke.

RCTs - Open-label oral anticoagulants versus control or double-blind anticoagulant treatment versus placebo.

2

485

Composite event of vascular death, nonfatal stroke, nonfatal MI or systematic embolism.

Patients with non-rheumatic AF and a previous history of TIA or minor ischaemic stroke. Only included patients without contraindications to anticoagulants.

Anticoagulation (INR 2.5-4.0 in one study).

Saxena and Koudstaal [28]

Anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-rheumatic atrial fibrillation and a history of stroke or TIA.

To compare the value of anticoagulant and antiplatelet therapy for the long-term prevention of recurrent vascular events in patients with non-rheumatic AF.

RCTs comparing anticoagulants to antiplatelets in patients with prior TIA or stroke.

2

1371

Composite event of vascular death, nonfatal stroke, nonfatal myocardial infarction or systematic embolism.

Patients with non-rheumatic AF and a previous history of TIA or minor ischaemic stroke. Excluded patients with poorly controlled hypertension.

Anticoagulation (INR 2.5-4.0 in one study; 2.4-3.0 in the other).

Kimachi et al. [29]

Direct OAC versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease

To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD.

RCTs and quasi-RCTs (RCTs in which treatment allocation was by predictable methods such as date of birth) comparing DOAC with warfarin.

5

12,545

Composite of all strokes and systemic embolic events. Major bleeding or symptomatic bleeding in a critical area or organ.

Eligible participants were diagnosed with non-valvular AF and moderate kidney impairment, defined as CrCl or eGFR between 15 and 60 mL/min.

DTIs including apixaban, dabigatran, edoxaban, and rivaroxaban as well as any other intervention classified as DOAC. Warfarin was to be dose-adjusted using INR.

Lafuente-Lafuente et al. [30]

Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation

To determine in patients who have recovered sinus rhythm after having AF, the effects of long-term treatment with antiarrhythmic drugs on death, stroke, embolism, drug adverse effects and AF recurrence.

RCTs comparing any antiarrhythmic drug with a control in adults who had AF and in whom sinus rhythm was restored.

59

21,305

Mortality, Embolic complications, and adverse events.

Adults (> 16 years) who had AF of any type and duration and in whom sinus rhythm had been restored, spontaneously or by any therapeutic intervention.

Oral long-term treatment with any available antiarrhythmic drug, at an appropriate dosing regime, aimed at preventing new episodes of AF.

Salazar et al. [31]

Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation

To assess comparative safety and efficacy of long-term anticoagulation using DTIs versus VKAs on vascular deaths and ischaemic events in people with non-valvular AF.

RCTs comparing DTIs versus VKAs for prevention of stroke and systemic embolism in people with non-valvular AF.

8

27,557

Vascular death + ischemic events, major bleeding. Composite outcome of vascular deaths and ischaemic events. Composite outcome of fatal or non-fatal major bleeding events.

People with non-valvular AF and one or more risk factors for stroke.

DTIs at standard doses compared with VKAs (adjusted-dose warfarin) for an INR between 2 and 3.

Nyong et al. [32]

Efficacy and safety of ablation for people with non-paroxysmal atrial fibrillation

To determine the efficacy and safety of ablation (catheter and surgical) in people with non-paroxysmal AF compared to antiarrhythmic drugs.

RCTs evaluating the effect of radiofrequency catheter ablation or surgical ablation compared with

antiarrhythmic drugs.

3

261

Freedom from atrial arrhythmias, or recurrence of any atrial arrhythmias.

Adult patients with persistent or long-standing persistent AF.

Radiofrequency catheter ablation technique.

Risom et al. [34]

Exercise-based cardiac rehabilitation for adults with atrial fibrillation

To assess benefits and harms of exercise-based rehabilitation programs, alone or with another intervention, compared with no exercise training in adults who currently have AF, or have been treated for AF.

RCT that investigated exercise-based interventions compared with any type of no-exercise control.

6

4 21

Mortality, serious adverse events, health-related quality of life.

Adult patients (18 years old or older) with AF, or who have been treated for AF.

Rehabilitation program with exercise training included. Exercise-based interventions were defined as: any rehabilitation program in an inpatient, outpatient, or community- or homebased setting.

Bruins and Berge [35]

Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with AF.

To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for preventing cerebral or systemic embolic events in people with AF.

RCTs that directly compared effects of long-term treatment with Factor Xa inhibitors vs. VKAs for preventing cerebral and systemic embolism in AF patients.

13

67,688

The composite endpoint of all strokes (both ischaemic and hemorrhagic) and other systemic embolic events.

People with AF who were eligible for treatment with anticoagulants.

Treatment with an oral or parenteral factor Xa inhibitor versus oral vitamin K antagonists (warfarin and congeners) with the intensity monitored using INR.

Moran et al. [39]

Systematic screening for the detection of atrial fibrillation

The primary objective of the review was to investigate whether evidence shows differences between systematic screening and routine practice in the detection of new cases of AF

RCTs and cluster-RCTs comparing systematic screening vs. routine practice.

1

9137

Primary outcome under investigation was the difference in the detection of new cases of AF associated with systematic screening compared with routine practice.

Men and women over the age of 40 years.

This was a diagnostic screening study so no intervention per se. Studies eligible for inclusion compared population-based, targeted or opportunistic screening program versus no screening.

Clarkesmith et al. [36]

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

To evaluate the effects of educational and behavioural interventions for OAC on TTR in AF patients.

RCTs evaluating the effect of any educational and behavioral intervention compared with usual care, no intervention, or intervention in combination with other self-management techniques.

11

2246

Primary outcome measure was TTR.

Adults diagnosed with AF

All types of educational and behavioural interventions.

Chen et al. [37]

Catheter ablation for paroxysmal and persistent atrial fibrillation

The primary objective was to assess the beneficial and harmful effects of catheter ablation in comparison with medical treatment in patients with paroxysmal and persistent AF.

RCTs in people with paroxysmal and persistent AF treated by any type of ablation method.

7

3560

Recurrence of AF, fatal and non-fatal embolic complications. All-cause mortality, death due to thrombo-embolic events.

Patients with paroxysmal and persistent AF.

Any type of catheter ablation, including pulmonary vein electrical isolation, superior vena cava isolation, left atrium posterior wall ablation and others.

Mead et al.* [40]

Electrical cardioversion for atrial fibrillation and flutter

To assess effects of cardioversion of AF/ flutter on risk of thromboembolic events, strokes and mortality, the rate of cognitive decline, quality of life, the use of anticoagulants and risk of re-hospitalisation.

RCTs of electrical cardioversion plus ‘usual care’ vs. ‘usual care’ only.

3

927

Primary outcome: risk of stroke, peripheral embolism, and death.

Adults with paroxysmal, sustained or permanent AF or atrial flutter.

Electrical cardioversion used as a first intervention plus ‘usual care’ versus ‘usual care’ only. ‘Usual care’ included drugs for ‘rate control’, anticoagulants or antiplatelet drugs.

Heneghan et al. [38]

Self-monitoring and self-management of oral anticoagulation

To evaluate effects on thrombotic events, major hemorrhages, and all-cause mortality of self-monitoring or self-management of oral anticoagulation compared with standard monitoring.

RCTs assessing the therapeutic effectiveness and safety of self-monitoring or self-management of oral anticoagulation therapy.

28

8950

Primary outcomes were thromboembolic events, all-cause mortality, major haemorrhage, TTR.

All patients on long-term OAC (treatment duration longer than two months), irrespective of the indication for treatment.

Self-monitoring or self-management of oral anticoagulation

  1. AF Atrial Fibrillation, CKD Chronic Kidney Disease, CrCl Creatinine Clearance, DOAC Direct Thrombin Inhibitor, DTI Direct Thrombin Inhibitor, eGFR Estimated Glomerular Filtration Rate, INR International Normalized Ratio, OAC Oral Anticoagulant, RCT Randomized Controlled Trials, TIA Transient Ischemic Attack, TTR Time in Therapeutic Range
  2. *This review was subsequently withdrawn.