Health Policy Advisory Committee on Technology

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1 Health Policy Advisory Committee on Technology Technology Brief Catheter ablation for atrial fibrillation July 2014

2 State of Queensland (Queensland Department of Health) 2014 This work is licensed under a Creative Commons Attribution Non-Commercial No Derivatives 3.0 Australia licence. In essence, you are free to copy and communicate the work in its current form for non-commercial purposes, as long as you attribute the authors and abide by the licence terms. You may not alter or adapt the work in any way. To view a copy of this licence, visit For further information, contact the HealthPACT Secretariat at: HealthPACT Secretariat c/o Clinical Access and Redesign Unit, Health Service and Clinical Innovation Division Department of Health, Queensland Level 2, 15 Butterfield St, HERSTON QLD 4029 Postal Address: GPO Box 48, Brisbane QLD HealthPACT@health.qld.gov.au Telephone: For permissions beyond the scope of this licence contact: Intellectual Property Officer, Department of Health, GPO Box 48, Brisbane QLD 4001, ip_officer@health.qld.gov.au, phone (07) Electronic copies can be obtained from: DISCLAIMER: This Brief is published with the intention of providing information of interest. It is based on information available at the time of research and cannot be expected to cover any developments arising from subsequent improvements to health technologies. This Brief is based on a limited literature search and is not a definitive statement on the safety, effectiveness or costeffectiveness of the health technology covered. The State of Queensland acting through Queensland Health ( Queensland Health ) does not guarantee the accuracy, currency or completeness of the information in this Brief. Information may contain or summarise the views of others, and not necessarily reflect the views of Queensland Health. This Brief is not intended to be used as medical advice and it is not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for a health professional's advice. It must not be relied upon without verification from authoritative sources. Queensland Health does not accept any liability, including for any injury, loss or damage, incurred by use of or reliance on the information. This Brief was commissioned by Queensland Health, in its role as the Secretariat of the Health Policy Advisory Committee on Technology (HealthPACT). The production of this Brief was overseen by HealthPACT. HealthPACT comprises representatives from health departments in all States and Territories, the Australian and New Zealand governments and MSAC. It is a sub-committee of the Australian Health Ministers Advisory Council (AHMAC), reporting to AHMAC s Hospitals Principal Committee (HPC). AHMAC supports HealthPACT through funding. This brief was prepared by Linda Mundy from the HealthPACT Secretariat.

3 Technology, Company and Licensing Register ID WP189 Technology name Catheter ablation for atrial fibrillation Patient indication Patients with paroxysmal atrial fibrillation Reason for assessment This Brief was commissioned in response to horizon scanning activities that identified an exponential growth in the rate of catheter ablation procedures for atrial fibrillation (AF) being conducted in Australia and New Zealand. With an increase in the population prevalence of atrial fibrillation, this trend has implications for health-care expenditure and policy. In addition, recent literature has described uncertainty in the evidence base describing the safety and long-term effectiveness of catheter ablation. In September 2012, the National Health Committee (NHC) of New Zealand completed a Technology Note on the use of catheter ablation for atrial fibrillation 1 (see Attachment 1). The Technology Note highlights several issues: the increasing prevalence of AF, the corresponding increase in the use of catheter ablation and the subsequent budgetary impact on the public health system, and the potential need for service reorganisation, assessing workforce and infrastructure capacity, in order to meet demand. To avoid duplication of effort, this Technology Brief will only present the most recent evidence around this topic, and as such will be an abbreviated version of a Brief. Stage of development in Australia Yet to emerge Experimental Investigational Nearly established Established Established but changed indication or modification of technique Should be taken out of use Licensing, reimbursement and other approval Numerous catheters for the use of cardiac ablation and electrophysiological mapping are registered on the ARTG. In addition, several mapping and navigation systems are registered including Ensite NavX (St Jude Medical Inc, USA) and CARTO (Biosense Webster Inc, USA). In addition, robotic systems such as the Niobe (Stereotaxis Inc, USA) and the Sensei (Hansen Medical, USA), which perform guidance, mapping and ablation remotely, have been developed but as yet not registered on the ARTG. Catheter ablation for atrial fibrillation: July

4 Australian Therapeutic Goods Administration approval Yes ARTG number (s) No Not applicable Technology type Technology use Procedure Therapeutic Patient Indication and Setting Disease description and associated mortality and morbidity See page three of the NHC s Technology Note. 1 A normal heart contracts 60 to 100 times per minute. Contraction of the atria is initiated by electrical signals which emanate from the sinus node, situated at the top of the right atrium. These electrical signals travel rapidly throughout the atria to ensure that all muscle fibres contract in the appropriate sequence, pushing the blood into the ventricles. The atrioventricular node passes on these electrical signals, causing the ventricles to contract after they have filled with blood from the atria. This normal, regular heart rhythm is referred to as sinus rhythm (Figure 1). 2 Figure 1 The normal heart and electrocardiogram (ECG) trace 3 Abnormal electrical signals, originating from the pulmonary veins, cause the muscle fibres in the atria to contract out of time, resulting in atrial fibrillation (AF) (Figure 2). These abnormal signals may pass on to the ventricles, causing a rapid and irregular heartbeat. Patients with AF may be aware of this irregular heartbeat and feel a fluttering of the heart. Symptoms include an irregular pulse, fatigue, exercise intolerance, dizziness, fainting Catheter ablation for atrial fibrillation: July

5 and general weakness as the heart is not working efficiently. AF may occur as a one-off episode, or may be paroxysmal or persistent. 2 Figure 2 Heart and ECG trace demonstrating AF 3 AF is the most common sustained cardiac rhythm disturbance, affecting approximately two per cent of the population. The prevalence of AF increases with age with approximately five per cent of individuals aged over 65 years affected. Haemodynamic impairment and thromboembolic events related to AF result in significant morbidity, mortality, and cost. The most common causes of AF include long-term high blood pressure and coronary heart disease, valvular heart disease and, less commonly, hyperthyroidism. 2 Atrial fibrillation may result in stroke, which is the most common cause of cerebrovascular death. Stroke occurs when a blood vessel leading to the brain is blocked by a clot (ischaemic stroke) or bleeds (haemorrhagic stroke). Although haemorrhagic strokes are less common than ischaemic strokes they have a higher fatality rate. As well as causing death, stroke results in high levels of disability in the community. An estimated 60,000 stroke events occur in Australia every year and the majority of these (70%) are first-ever strokes. 4 In people aged over 65 years with untreated AF, the risk of experiencing a stroke is approximately one in 20, which is five to six times higher than in those without AF. The risk of stroke increases in individuals with AF and other co-morbidities, including diabetes and high blood pressure. 2 In 2009, there were 8,300 deaths from stroke in Australia, accounting for six per cent of all deaths and 18 per cent of deaths from cardiovascular disease. During the same period, stroke was the second leading cause of death for females behind coronary heart disease accounting for 6,706 or 9.8 per cent of all deaths. Stroke was the third leading cause of death in males behind coronary heart disease and lung cancer, accounting for 4,514 or 6.2 per cent of all male deaths. Although more females died from stroke in 2009, the rate of death per 100,000 population was higher for males than females (36.0 vs 33.9, respectively). 5 Catheter ablation for atrial fibrillation: July

6 During there were 41,977 public hospital separations for cerebrovascular diseases (I60 I69). Of these, the greatest proportion was for cerebral infarction (I63) with 17,079 separations (ALOS 10.0 days) followed by stroke (I64, not specified as haemorrhage or infarction) with 8,021 separations (ALOS 8.0 days). 4 Number of patients A recent Australian study by Kumar et al (2013) reported on the 10-year trend in the use of catheter ablation for AF using data obtained from the AIHW a procedures database, Medicare Benefits Schedule (MBS) item usage and from the Royal Melbourne Hospital (RMH), a tertiary referral centre for electrophysiology and ablation of cardiac arrhythmias. 6 All of these sources are problematic, highlighting the difficulty policy makers have in accessing accurate usage data for many interventions conducted in Australia. The AIHW data, whilst inclusive of procedures conducted in both public and private Australian hospitals, has used a number of classifications over the years to describe ablation of arrhythmia. For the purposes of this study data from the years 2000 to 2010 were collected using the classification of ablation of arrhythmia circuit or focus involving two atrial chambers, which was considered to most accurately represent the MBS item number for AF ablation. Similarly, there is no specific MBS billing code for AF ablation alone, with the most appropriate MBS item number for this indication considered to be ablation of arrhythmia circuits of foci, or isolation procedure involving both atrial chambers and including curative procedures for atrial fibrillation. However, MBS item number usage statistics only reflect private hospital activity. The RMH data were used to validate the trends observed in the AIHW and MBS data. The AIHW data revealed that AF ablation constituted 28 per cent of all ablation procedures, and that over the 10-year period the number of AF ablation increased from to 0.04 procedures per 1,000 persons, representing a 30.9 per cent per year population-adjusted increment (95%CI [21.1, 41.8] % per year, p< 0.001). This rate was significantly higher than the increment rate for all cardiovascular procedures (3.8%, p= 0.002) and for percutaneous coronary interventions (PCI) (5.1%, p=0.004) over the same period. This held true after a sensitivity analysis was conducted to address possible errors in coding for the procedure. This upward trend for AF ablation procedures was confirmed by the data obtained from the MBS, where over the same 10-year time period, AF ablations increased from 0.01 to 0.07 procedures per 1,000 persons. This increase translated to a 23.2 per cent per year population-adjusted increment (95%CI [18.9, 27.8] % per year, p< 0.001). Similarly, this rate was significantly higher than the number of PCIs performed during the same time (5%, p<0.001). Tertiary hospital data from the RMH confirmed this trend, with absolute numbers a AIHW = Australian Institute of Health and Welfare Catheter ablation for atrial fibrillation: July

7 of AF ablations increasing from 16 in 2001/02 to 200 in 2009/10, an increase of 39.8 per cent per year. 6 To confirm this trend, the number of procedures using the MBS item number were obtained and plotted for the past 10 years (Figure 3), indicating a steady increase in item usage over time. Figure 3 The number of procedures using MBS item number 38290, The authors concluded that with the given population prevalence of AF, that healthcare expenditure for AF will rise exponentially, with concomitant implications for health policy, especially in the areas of infrastructure, workforce and training of appropriate personnel, and funding for catheter ablation for AF. 6 In there were 51,381 public hospital separations for atrial fibrillation and flutter (I48) with an average length of stay of 3-days. This represents an increase of five per cent from the 48,869 separations recorded during The majority of these cases (76%) occurred in patients aged 60 years and over. 7 Speciality Technology setting Cardiovascular Specialist or general hospital Impact Alternative and/or complementary technology Additive and substitution: Technology can be used as a substitute in some cases, but may be used in combination with current technologies in other instances. Catheter ablation for atrial fibrillation: July

8 Current technology A number of options are available for the treatment of atrial fibrillation depending on the severity of the symptoms, including medication, cardioversion or ablation procedures. Initial treatment should be designed to control ventricular rate, especially in elderly patients. This may later be supplemented by interventions to control rhythm, including medication or ablation. 8 Most patients diagnosed with AF will be prescribed an anticoagulant, often either aspirin or warfarin, to prevent clot formation. Although warfarin is more effective than aspirin in reducing the risk of stroke, it is associated with severe side effects including excessive bleeding due to its mode of action blocking multiple active vitamin K-dependent coagulation factors. 2 It should be noted that several new oral anticoagulants are now on the market (dabigatran, rivaroxaban and apixaban), which block the activity of only one single step in the coagulation process, however these drugs may be associated with major bleeding events that are equal to, or less than those experienced with warfarin. 9 In addition, patients may be prescribed medication which aims to slow the heart rate by increasing the time taken for the ventricles to fill and contract (beta-blockers, digoxin and some calcium channel blockers). Anti-arrhythmic drugs (AADs) may also be prescribed, including solatol, flecainide and amiodarone, which aim to maintain a normal heart rhythm. 2 Some AADs are contraindicated in some patients due to their negative inotropic and pro-arrhythmic effects. In addition, some AADs are associated with side effects including bradycardia, photosensitivity, thyroid dysfunction and liver toxicity. 19 Cardioversion, either electrical or pharmacological, aims to restore a normal heart beat after a prolonged or severe episode of AF. During electrical cardioversion, the patient is sedated or anaesthetised and an electrical shock is applied to the heart via external defibrillator pads placed on the chest. The shock is synchronised to correspond to the R wave of the QRS complex on the ECG. Ventricular fibrillation may be induced if the electrical shock is delivered during the refractory period on the ECG. The same anti-arrhythmic drugs, as described above, which may be given long-term to maintain patients with AF after electrical cardioversion, may be prescribed to achieve pharmacological cardioversion. The treatment pathway for patients with or without structural heart disease, as outlined in the 2010 European guidelines for the treatment of AF, is described in Figure 4. 8 A number of new technologies are being developed to improve non-surgical techniques for AF including: VytronUS, a low-intensity collimated ultrasound ablation system; focussed ablation by cyclotron; radiosurgery; atrial rotor mapping; laser ablation and atrial rotor mapping (personal correspondence Queensland Health). 2, 10 Catheter ablation for atrial fibrillation: July

9 Figure 4 Treatment pathway for patients with and without structural heart disease HT = hypertension, LVH = left ventricular hypertrophy, CHF = congestive heart failure, CAD = coronary heart disease, NYHA = New York Heart Association Functional Classification 8 Cost infrastructure and economic consequences See page 18 onwards of the NHC s Technology Note. As an indication of the increase in costs to the health system for AF ablation procedures over time, Figure 5 demonstrates the increase in benefits payable for MBS item number 38290, which attracts a fee of $2, and a 75 per cent benefit of $2,004. It should be noted that this MBS item number underestimates the true cost of catheter ablation as it does not include the cost of the device or diagnostic tests associated with the procedure. The benefit paid in was $671,764, which increased steadily with the increasing number of procedures performed to $4,779,610 in , an increase of 611 per cent over the 10-year period. The true cost to the public system of catheter ablation for AF is difficult to ascertain due to the procedure being grouped under the same DRG as numerous other catheter-based cardiac procedures. Of note, are potential costs arising from patients with undiagnosed atrial fibrillation who then experience a stroke. Patients with untreated atrial fibrillation have a risk of five per cent each year to develop stroke. In Australia, the total financial costs of stroke were estimated to be $5 billion in 2012, with health costs of $881 million, the majority of which are borne by the Commonwealth ($376 million) and the States ($233 million). 18 The risk of stroked in AF patients is greatly reduced with treatment. Catheter ablation for atrial fibrillation: July

10 Figure 5 The $ Benefit payable for MBS item number from July 2003 to June Ethical, cultural or religious considerations See pages 16 and 17 of the NHC s Technology Note. Evidence and Policy In early 2013 the National Heart Foundation of Australia issued a consensus statement of the use of catheter ablation for AF. Although these recommendations are designed for healthcare providers, they are not viewed as clinical practice guidelines due to the limited evidence on the use of catheter ablation for AF available at the time. Only one recommendation could be graded according to the NHMRC levels of evidence. As such, the consensus recommendations are largely based on the expert opinion of the members of the National Heart Foundation s working group. 11 The recommendations state that the current evidence base supports the use of catheter ablation as a means to improve the quality of life of patients with AF by relieving symptoms of an irregular rhythm and a rapid ventricular rate including breathlessness, fatigue, lightheadedness and palpitations. However, there is currently a lack of evidence to support the use of AF catheter ablation to decrease the risk of stroke and heart failure. The consensus statement recommends that: Catheter ablation should only be carried out in symptomatic patients who are refractory or intolerant to at least one Class 1 or Class 3 antiarrhythmic drug (recommendation based on level I intervention evidence). Cessation of anticoagulant therapy is not considered a sole indication for catheter ablation. Some asymptomatic AF patients may seek ablation as a means to cease Catheter ablation for atrial fibrillation: July

11 taking anticoagulation medication, however there is insufficient evidence to support the cessation of medication over the long-term (consensus). Clinicians should consider the age of the patient presenting for the ablation procedure, with improved results reported in younger patients (age not specified) with paroxysmal AF with no significant structural heart disease or marked atrial enlargement (consensus). Post-ablation patients should continue anticoagulation therapy for 1-3 months. Discontinuation of anticoagulation therapy is not recommended for patients with a CHADS 2 score b Safety and effectiveness The NHC Technology Note reported on the results of eight RCTs, which indicated that per cent of patients were free from AF at 12 months after catheter ablation, compared with 4-43 per cent of those treated with AADs alone. There was an 11-40% repeat procedure rate. A Cochrane review of seven small RCTs reported that catheter ablation was more effective at inhibiting the recurrence of AF (RR 0.27; 95% CI [0.18, 0.41]). However there was significant heterogeneity between the studies with mixed paroxysmal, persistent and some chronic AF patient populations of differing ages (I 2 =72%, p=0.002). In terms of safety there were no differences between catheter ablation and medical treatment in death, fatal and non-fatal embolic complications. 12 Since the NHC Technology Note was written, several studies have been published, the most recent being the latest follow-up results from the RAAFT-2 c randomised controlled trial (RCT) (level II intervention evidence). This relatively small multicentre RCT randomised treatment naïve patients with paroxysmal AF to receive either AAD (n=61) or catheter ablation (CA, n=66) as a first-line treatment. There was no difference in the patient characteristics between the two groups. The majority of patients were male (73.8 and 77.3%) with a mean age of 56.3 (± 9.3) and 54.3 (±11.7) years in the CA and AAD groups, respectively. Each patient received a monitoring system to record episodes of symptomatic AF, with adherence defined as the transmittance of at least 75 per cent of required recordings. AADs were titrated or ablation was performed during a 3-month blanking period. 13 b CHADS 2 score is a clinical prediction rule for estimating the risk of stroke in patients with AF. Scores range from 0 to 6, with points allocated according to the presence of symptoms: congestive heart failure =1; hypertension = 1; age 75 years = 1; diabetes = 1 and prior stroke, thromboembolism or transient ischemic attack = 2. Patients with a CHADS 2 score of 2 have a 4.0% risk of stroke, with the risk increasing with an increasing CHADS 2 score (European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery et al. 2010) c RAAFT-2 = Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation Catheter ablation for atrial fibrillation: July

12 CA was performed in 63 of the 66 patients randomised to undergo the procedure. At 21 months follow-up, nine patients (13.6%) in the CA group had undergone a repeat procedure and six (9.09%) had crossed over to the AAD arm. In addition, three patients from the AAD arm crossed over to the CA arm. Results were reported on an intention-to-treat basis. Overall, adequate transmittance of recordings were completed by 83 per cent of patients with no difference between the CA (86.4%) and AAD (78.7%) arms. 13 There were no reported deaths or strokes in either group. Six patients in the CA arm experienced a serious adverse event (9.1%), including tamponade (n=4), severe pulmonary vein stenosis 70% (n=1) and bradycardia leading to the insertion of a pacemaker (n=1). A serious adverse event was reported in three patients in the AAD arm (4.9%), with two patients experiencing syncope and one atrial flutter with 1:1 atrioventricular conduction. Quality of life was measured by the EQ-5D tool, which measures health across five areas: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression, with a worst score of zero and a score of one indicating excellent health. There was no difference in median EQ-5D scores between the two groups at baseline (p>0.99) or at 12-months follow-up (p=0.25). Although the EQ-5D score improved in both groups from baseline to 12- months the change was only significant in the CA group (p= 0.03) and not the AAD group (p = 0.22). The primary and secondary effectiveness outcomes are summarised in Table 1. Although there was a significant difference between the two groups in the rate of recurrent atrial tachyarrhythmia as documented by patient transmitted data, it is unclear whether this difference would be considered clinically significant. When only clinically identified events were considered the difference between groups was abolished with 24 and 31 per cent of patients in the CA and AAD arms, respectively, experiencing an event (HR 0.86, 95% CI [0.42, 1.72], p=0.66). In addition, it should be noted that recurrence was common in both groups reported in almost 50 per cent of patients. This study is limited by its small size and the fact that all patients were relatively young with little or no evidence of structural heart disease as would be expected in a normal clinical population. Therefore caution should be advised when considering catheter ablation as a first-line treatment option for AF. Catheter ablation for atrial fibrillation: July

13 Table 1 Primary and secondary outcomes of the RAAFT-2 trial 13 CA arm n (%) AAD arm n (%) Hazard ratio [95% CI] p value Recurrence of any atrial tachyarrhythmia lasting longer than >30 seconds 36 (54.5%) 44 (72.1%) 0.56 [0.35, 0.90] 0.02 First recurrence of symptomatic AF, atrial flutter and atrial tachycardia 31 (47%) 36 (59%) 0.56 [0.33, 0.95] 0.03 First recurrence of symptomatic AF 27 (41%) 35 (57%) 0.5 [0.3, 0.89] 0.02 First recurrence of symptomatic AF, atrial flutter and atrial tachycardia not recorded by monitor 16 (24%) 19 (31%) 0.86 [0.42, 1.72] 0.66 Total number of AF, atrial flutter and atrial tachycardia (multiple recurrences, using a recurrence event model) 213 (6.6%) 502 (14.7%) 0.33 [0.28, 0.4] <0.001 CA = catheter ablation, AAD = Anti-arrhythmic drugs, AF = atrial fibrillation These positive results contrast with those published in late 2012 by Nielsen et al who conducted the larger MANTRA-PAF d RCT, which randomised treatment naïve patients with paroxysmal AF to receive either AAD (n=148) or catheter ablation (n=146) as a first-line treatment (level II intervention evidence). Similar to the RAAFT-s study the majority of patients were relatively young (mean 55 ± 10 years) males (68-72%). There was no difference in the baseline characteristics between the two groups. Clinical follow-up and 7- day Holter monitoring was conducted at 3, 6, 12, 18 and 24-months, with Holter analysis blinded with respect to randomisation. The primary outcome was the burden of AF as defined by the percentage of time spent in AF on each Holter recording and the cumulative burden of AF as defined as the percentage of time spent in AF during all Holter recordings. 14 A total of 140 (96%) patients underwent a mean of 1.6 ± 0.7 ablation procedures. At 24- months follow-up, 58 patients had undergone two, eight patients had three, and three patients had four catheter ablation procedures. Reasons for repeat ablations were left atrial arrhythmia (n=79 procedures), right atrial flutter (n=2), atrioventricular nodal re-entrant tachycardia (n=1) and focal atrial tachycardia (n=1). In addition, 13 patients from the CA arm had crossed over to the AAD arm. The majority of patients in the AAD arm received a class IC AAD (n=131) with the remaining receiving a class III AAD. The mean number of AADs prescribed to patients was 1.26 ±.046 (range 1-3). CA was performed in 54 (36%) patients d MANTRA-PAF = Medical antiarrhythmic treatment or radiofrequency ablation in paroxysmal atrial fibrillation Catheter ablation for atrial fibrillation: July

14 from the AAD arm at a mean time of 8.7 ± 6.5 months post-randomisation. These patients underwent a mean of 1.6 ± 0.7 ablations for left atrial arrhythmia (n=81 procedures) and right atrial flutter (n=6). 14 There was no difference in the number of serious adverse events with 25 and 22 reported in the CA and AAD arms, respectively (p=0.45). Three patients in the CA and four patients in the AAD group died during the study, with one death in the CA group considered to be a procedure-related cerebral stroke. The other causes of death were not considered to be related to the treatment. The more serious adverse events in each group are summarised in Table 2. Quality of life at baseline, as measured by the SF-36, did not differ between the two groups at baseline. Quality of life improved in both treatment groups, however there was a greater improvement in the physical component of patients in the CA arm. 14 Table 2 Number of serious adverse events 14 CA arm AAD arm Death 3 4 Atrial flutter with 1:1 atrioventricular conduction 0 2 Atrial flutter or atrial tachycardia 3 3 Perimyocarditis 1 0 Stroke 1 0 Transient ischaemic attack 1 1 Tamponade 3 0 Pericardial effusion without the need for pericardial puncture 0 1 Suspected perforation at transeptal puncture, no pericardial effusion 1 0 Pulmonary vein stenosis 1 0 Hospitalisation for heart failure 0 2 Holter recordings were available for analysis from 96 per cent of follow-up visits. There was no reported difference in the cumulative AF burden, as assessed with 7-day Holter monitors during the 24-month follow-up between the CA and AAD arms (90th percentile of arrhythmia burden, 13% vs 19%, respectively, p=0.10). The AF burden was significantly lower at each follow-up point in both treatment groups when compared to baseline (p<0.001 for all comparisons). Although there was no difference between the two groups in the burden of AF at 3, 6, 12 or 18-month follow-up, at 24-months the AF burden was significantly lower in the CA group compared to patients in the AAD arm (90th percentile, Catheter ablation for atrial fibrillation: July

15 9% vs 18%, p=0.007). In addition, more patients in the CA group were free from any AF (85% vs 71%, p=0.004) and from symptomatic AF (93% vs 84%, p=0.01) compared to the AAD arm at 24-months. Of interest is the report, commissioned by the Belgian Government, which analysed the outcome of all patients who underwent a first catheter ablation for AF (level IV intervention evidence). Data were obtained from a nationwide health insurers database, with all claims of patients being retrieved between November 2007 and December During this time 1,030 patients underwent catheter ablation, however only 830 patients underwent the procedure for the first time, the majority of whom were male (71.9%) with a mean age of 58 years. The majority of patients had paroxysmal AF (77%). 15 Patient outcomes are summarised in Table 3. AAD usage was not considered during the of 3- month post-ablation blanking period. Although patients were followed up for a mean period of 30.2 months, AAD usage was only obtained for the 24-month period post-ablation. At the end of follow-up a total of 214 patients (25.8%) underwent one or more repeat ablations. Of these, 30 patients required two, one required three and another required four repeat procedures. The average number of ablations per patient was 1.3 over the follow-up period. In addition, at the end of follow-up, cardioversion was performed in 218 (26.3%) patients, at a mean time of 220 days post-ablation (median 118 days). Using AAD use one month after the blanking period as a measure of ablation failure, AF was estimated to recur in 37.3 and 49.9 per cent of patients at 12 and 24-months, respectively (model 1 or 2 or 3c). There was no relationship between the patient s age, risk profile and the rate of AF recurrence. Using pre and post-ablation prescription data it was estimated that up to 15.8 per cent of patients had undergone catheter ablation as a first-line AF treatment. 15 These results were extracted from a full health technology assessment, which also intended to conduct a cost-effectiveness analysis of catheter ablation for AF. However, this analysis could not be conducted due to the lack of reported data on endpoints such as quality of life, mortality and stroke. Costs from the healthcare payer perspective for catheter ablation in this study were estimated to be 9,600 for the initial intervention, compared to 300 per year for a combination of rate and rhythm control drugs. 15 Catheter ablation for atrial fibrillation: July

16 Table 3 Patient outcomes 12 and 24-months post-catheter ablation 15 Model Pre-ablation n (%) Follow-up 3-12 month, n (%) Follow-up 3-24 month, n (%) Follow-up 30.2 months, n (%) Repeat ablation (16.1%) 192 (23.1%) 214 (25.8%) Electric cardioversion 2 94 (11.3%) 145 (17.5%) 218 (26.3%) AAD use At least 1 AAD 3a 667 (80.4%) 456 (54.9%) 504 (60.7%) At least 1 AAD with non-amiodarone* 3b 296 (35.7%) 386 (46.5%) At least 1 AAD with an AAD-free window of 1 month beyond the blanking period Combinations 3c 211 (25.4%) 315 (38.0%) 1 or 2 or 3a 496 (59.8%) 547 (65.9%) 1 or 2 or 3b 378 (45.5%) 464 (55.9%) 1 or 2 or 3c 310 (37.3) 414 (49.9%) AAD = Anti-arrhythmic drugs * At least one AAD used beyond the blanking period, taking into account that for non-amiodarone AADs an AAD-free window of 1-month beyond the blanking period is considered. Another large European observational study captured 12-month follow-up catheter ablation data from 72 centres in 10 European countries (level IV intervention evidence). Each centre was required to recruit at least 20 consecutive patients undergoing their first CA procedure for AF. A total of 1,391 patients from a mixed AF population underwent CA, with one patient dying during the in-hospital phase. At 12-months, 1,300 (93.5%) patients were available for follow-up (67% paroxysmal AF, 27.4% persistent AF, 4.5% permanent AF and 1.1% undefined). The majority of patients were male (71.8%) with a median age at follow-up of 60 years (interquartile range years). Most patients had preserved cardiac function with only three and two per cent having dilated cardiomyopathy and chronic heart failure, respectively. The most commonly used technology was radiofrequency ablation (80%) followed by cryoablation (11%). 16 A clinical visit at 12-month follow-up was only completed by 58.2 per cent of patients, with the remaining patients being contacted by telephone regarding their symptoms, however 87.2 per cent of all patients had at least one ECG during the follow-up period. Success of CA was defined as patient survival free from any AF, with or without AADs, after the 3-month blanking period. Arrhythmia recurrence was defined as an ECG documented episode of AF lasting at least 30 seconds. 16 Although an overall success rate of CA was reported to be 72.6 per cent, this included patients with or without the use of AADs at 12-months. In the absence of AADs, a successful ablation procedure was reported in 40.3 per cent of all patients, with the highest rate of Catheter ablation for atrial fibrillation: July

17 43.7 per cent reported in patients with paroxysmal AF (Table 4). Overall 18.3 per cent of patients in the success group required a second ablation procedure. In addition, 34.4 per cent of patients considered to be a success still reported symptoms including palpitations, dyspnoea and fatigue. Complete follow-up data were available for 1,281 patients, of whom 337 (26.3%) experienced a recurrence after the 3-month blanking period. Patients with nonparoxysmal AF had a higher probability of recurrence compared to those with paroxysmal (43.6% vs 32.0%, p<0.0001). Asymptomatic recurrences occurred in 25.8 per cent of patients. 16 At 12-month follow-up, 65 per cent of all patients were taking an anticoagulant. Interestingly, 24 per cent of those patients with a CHADS 2 score >1 were not receiving anticoagulation, however 48 per cent of those patients considered to be at low risk with a CHADS 2 score = 0 were still receiving anticoagulation therapy, indicating differences in clinical practice from that recommended by guidelines. A total of five deaths were reported, three of which were considered to be procedurerelated. The rate of adverse events was reported to be 2.5 per cent, of which 0.8 per cent were considered to be major. More than one third were considered to be procedure related (37.5%). A pacemaker was inserted in 13 patients, there were nine vascular and seven cerebrovascular injuries, two phrenic nerve injuries and one case of pulmonary vein stenosis. If post-ca atrial tachycardia/flutter was included as a complication, the rate of adverse events increases to 26.5 per cent. 16 The lower success rate when compared to other studies may be attributed to the mixed patient population, different ablation techniques (differences not analysed), variation between operators and variation in type and accuracy of follow-up. Table 4 Success of catheter ablation by AF type 16 Type of AF Success without AADs Success with AADs Overall success Paroxysmal (n=871) 381 (43.7%) 256 (29.4%) 647 (74.3%) Persistent (n=265) 80 (30.2%) 99 (37.4%) 191 (72.1%) Long-lasting persistent (n=90) 33 (36.7%) 18 (20.0%) 52 (57.8%) Overall (n=1226) 494 (40.3%) 373 (30.4%) 890 (72.6%) Catheter ablation for atrial fibrillation: July

18 Economic evaluation See page 14 onwards of the NHC s Technology Note. The most recent published systematic cost analysis was conducted by the Belgian Government. This review identified five studies as described by the NHC Technology Note in addition to two other papers. The conclusions of these studies are summarised in Table 5. Eckard et al (2009) and Reynolds et al (2010) considered CA a cost-effective second-line treatment for paroxysmal AF. This conclusion was based on assumptions that CA would impact on mortality from stroke, however there is a lack of long-term follow-up data from RCTs to support this assumption. CA is associated with high initial costs and patients may need to undergo repeat procedures in addition to taking AADs post-procedure. The authors therefore concluded that there was insufficient evidence to comment on the costeffectiveness of catheter ablation for the treatment of AF. 17 Table 5 Conclusions of economic evaluations retrieved on the cost-effectiveness of catheter ablation 17 Study Chan et al (2006) United States Ollendorf et al (2010) United States Assasi et al (2010) Canada Eckard et al (2009) Sweden Reynolds et al (2010) United States Rodgers et al (2008) McKenna et al (2009) United Kingdom Conclusion In patients with AF, catheter ablation is unlikely to be cost-effective in patients at low risk for stroke. In moderate-risk patients, catheter ablation may be cost-effective if sufficiently high efficacy rates in restoring sinus rhythm translate into lower morbidity. No explicit conclusion on the intervention s cost -effectiveness is drawn. There is only a high certainty of a small benefit for second-line ablation in paroxysmal AF patients. In other populations and for first-line ablation there is a potential but unproven benefit. The primary economic evaluation using a five-year time horizon found the incremental cost per QALY of AF ablation compared with AAD to be $59,194. The radiofrequency ablation treatment strategy was associated with reduced cost and an incremental gain in QALYs and was considered a cost-effective treatment strategy compared to the AAD in a lifetime perspective. Catheter ablation with/without AAD for symptomatic, drug-refractory paroxysmal AF appears to be reasonably cost-effective compared with AAD therapy alone from the perspective of the US healthcare system. The ICER for catheter ablation versus AAD was $51,431 per QALY applying a 5- year time horizon. The overall conclusions regarding the cost-effectiveness of catheter ablation appear to require that the QoL benefits are maintained for more than 5 years and/or that normal sinus rhythm has prognostic value in preventing the risk of stroke. If neither of these is considered to be realistic then the cost-effectiveness of catheter ablation remains highly uncertain. A full cost-effectiveness analysis may reveal differences in rates of health services usage before and after catheter ablation for AF. Ladapo et al (2012) examined patient records from health insurance plans in the United States. The number of outpatient and emergency department visits, in addition to number of hospitalised days, were compared in patients (n=3,194, mean age 58.2 ± 10.6 years) with AF for 6-months prior to catheter ablation and for 6-12-months post-ablation. There were significant reductions in the number of visits in all categories (Table 6), however there was a great deal of variation both pre- and postablation as indicated by the large standard deviations. 20 Catheter ablation for atrial fibrillation: July

19 Table 6 Outpatient, inpatient and hospitalisation usage pre- and post-catheter ablation for AF 20 Utilisation by type Before ablation 6-months Mean ± SD Post-ablation 6-12 months Mean ± SD p-value Number of outpatient office visits ± ± 7.82 <0.001 Number of outpatient hospital visits 4.74 ± ± 5.32 <0.001 Number of emergency department visits 0.71 ± ±.097 <0.001 Number of hospitalised days 1.59 ± ± 2.77 <0.001 Percent of patients with utilisation by type p-value Outpatient office visits 98% 96% Outpatient hospital visits 89% 69% <0.001 Emergency department visits 38% 21% <0.001 Hospitalisation 35% 18% <0.001 SD = standard deviation Ongoing research As described in the NHC Technology Note, the largest RCT comparing catheter ablation to AADs, the CABANA e trial, is still underway and recruiting patients. This RCT intends to recruit 2,200 patients with a mixed clinical diagnosis: 2 paroxysmal AF episodes lasting 1 hour in duration; or electrocardiographic documentation of one persistent AF episode; or electrocardiographic documentation of one longstanding persistent AF episode (continuous AF of duration >1 year). The CABANA Trial is designed to test the hypothesis that the treatment strategy of left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) will be superior to current state-of-the-art therapy with either rate control or rhythm control drugs for decreasing the incidence of the composite endpoint of total mortality, disabling stroke, e CABANA = Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial Catheter ablation for atrial fibrillation: July

20 serious bleeding, or cardiac arrest in patients with untreated or incompletely treated AF (NCT ). Other issues Other methods for the treatment of AF have been proposed, with several trials currently recruiting patients. A German RCT (Interventional Strategies in Treatment of Atrial Fibrillation: Percutaneous Closure of the Left Atrial Appendage Versus Catheter Ablation) aims to compare the percutaneous closure of the left atrial appendage (LAA) combined with a rate-control strategy to catheter ablation in the management of patients with persistent AF. This proposal is based on the results of the PROTECT AF study, where percutaneous closure of the LAA with a closure device provided an alternative strategy to oral anticoagulation for stroke prophylaxis (NCT ). A US and Russian RCT is currently recruiting 300 patients with paroxysmal AF and hypertension to determine the role of renal sympathetic denervation in the prevention of AF recurrence. Patients will be randomised to either AF catheter ablation or AF catheter ablation plus renal sympathetic denervation (NCT ). Summary of findings The prevalence of AF in Australia and New Zealand has increased over time, with a concomitant increase in the number of catheter ablation procedures being performed. Since the publication of the NHC Technology Note, two high-quality studies have been published describing the results of treatment naïve patients with paroxysmal AF randomised to either catheter ablation or antiarrhythmic drugs as a first-line treatment. Results from these RCTs were conflicting with one reporting a significantly lower rate of AF recurrence in CA treated patients, whilst the other reported no difference in the cumulative burden of AF between patients treated with CA and AADs. However, as the National Heart Foundation recommends, based on level I intervention evidence, that catheter ablation should only be carried out in symptomatic patients who are refractory or intolerant to at least one Class 1 or Class 3 antiarrhythmic drug, these results are not relevant to the Australian setting. The remaining two studies included in this assessment were large observational studies, and can therefore only inform a discussion around the safety, rather than the effectiveness of catheter ablation. All studies did, however, report that catheter ablation is associated with a number of potentially serious adverse events including stroke, tamponade and pulmonary vein stenosis. All studies reported rates of repeat catheter ablation procedures ranging from 13.6 to 47 per cent of patients, with some patients undergoing more than one repeat procedure, with each repeat procedure exposing the patient to the risk of experiencing a serious adverse event. In addition, continued AAD use post-catheter ablation is common. Long-term outcome data from large randomised controlled trials is lacking to inform a costeffectiveness analysis. Catheter ablation for atrial fibrillation: July

21 HealthPACT assessment Based on the information gathered to inform this Technology Brief, combined with the existing Technology Note from New Zealand, it is clear that the use of catheter ablation for AF will increase over time. Although the evidence base is weak in terms of long-term outcomes, such as the impact on mortality and reductions in the incidence of stroke, it should be noted that the risk of stroke is markedly reduced in patients treated for atrial fibrillation. There is also a lack of robust cost-effectiveness data on what appears to be an established procedure. Long-term effectiveness data from the CABANA Trial is still many years away from publication. HealthPACT noted that although catheter ablation was considered a common procedure, it should be remembered that it is an invasive procedure and as such is associated with risks. Australian jurisdictions and New Zealand should liaise with their cardiac networks to ascertain the level of activity and to consider the role of catheter ablation for atrial fibrillation with respect to appropriate patient selection and its role in the clinical pathway. Therefore it is recommended that no further research on behalf of HealthPACT is required. Number of studies included All evidence included for assessment in this Technology Brief has been assessed according to the revised NHMRC levels of evidence. A document summarising these levels may be accessed via the HealthPACT web site. Total number of studies 4 Total number of Level IV intervention studies 2 Total number of Level II intervention studies 2 Search criteria to be used (MeSH terms) Atrial Fibrillation/*drug therapy/prevention & control/*surgery *Catheter Ablation/methods Recurrence/prevention & control References 1. NHC (2012). NHC Technology Note for Catheter Ablation for the Treatment of Atrial Fibrillation, National Health Committee, Wellington, New Zealand Available from: 2. NHF (2008). Atrial fibrillation. [Internet]. National Heart Foundation of Australia. Available from: on_infc_ _final.pdf [Accessed 11th August 2010]. 3. NZGG (2006). Atrial fibrillation. [Internet]. New Zealand Guidelines Group Incorporated. Available from: [Accessed 11th August 2010]. Catheter ablation for atrial fibrillation: July

22 4. AIHW (2010). Australia s health 2010, Australian Institute of Health and Welfare, Canberra Available from: 5. AIHW (2012). Australia s health 2012, Australian Institute of Health and Welfare, Canberra Available from: 6. Kumar, S, Walters, TE et al (2013). 'Ten-year trends in the use of catheter ablation for treatment of atrial fibrillation vs. the use of coronary intervention for the treatment of ischaemic heart disease in Australia'. Europace, 15 (12), Separation, patient day and average length of stay statistics by principal diagnosis in ICD-10-AM, Australia, to [database on the Internet]. Australian Institute of Health and Welfare [Accessed 15th April]. Available from: 8. European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery et al (2010). 'Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC)'. Eur Heart J, 31 (19), Vergara, P & Della Bella, P (2014). 'Management of atrial fibrillation'. F1000Prime Rep, 6, Shea, JB & Maisel, WH (2002). Cardiology Patient Page - Cardioversion. [Internet]. American Heart Association. Available from: [Accessed 14th April 2014]. 11. Kalman, JM, Sanders, P et al (2013). 'National Heart Foundation of Australia consensus statement on catheter ablation as a therapy for atrial fibrillation'. Med J Aust, 198 (1), Chen, HS, Wen, JM et al (2012). 'Catheter ablation for paroxysmal and persistent atrial fibrillation'. The Cochrane database of systematic reviews, 4, Cd Morillo, CA, Verma, A et al (2014). 'Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial'. JAMA, 311 (7), Cosedis Nielsen, J, Johannessen, A et al (2012). 'Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation'. The New England journal of medicine, 367 (17), Van Brabandt, H, Neyt, M & Devos, C (2013). 'Effectiveness of catheter ablation of atrial fibrillation in Belgian practice: a cohort analysis on administrative data'. Europace, 15 (5), Arbelo, E, Brugada, J et al (2014). 'The Atrial Fibrillation Ablation Pilot Study: an European Survey on Methodology and * Results of Catheter Ablation for Atrial Fibrillation: conducted by the European Heart Rhythm Association'. Eur Heart J. 17. Neyt, M, Van Brabandt, H & Devos, C (2013). 'The cost-utility of catheter ablation of atrial fibrillation: a systematic review and critical appraisal of economic evaluations'. BMC Cardiovasc Disord, 13, Deloitte Access Economics (2013). The economic impact of stroke in Australia, National Stroke Foundation Available from: Catheter ablation for atrial fibrillation: July