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Anticoagulation and Cardiac Procedures
This section covers cardioversion, ablation and PCI in patients with AF, discussing guideline recommendations and data from clinical studies
In this section:
Cardioversion
Cardioversion aims to re-establish a normal sinus rhythm in patients with AF, either by:1,2
- 'Stunning' the left atrium using an electrical pulse (electrical cardioversion) or
- Using rate-modifying drugs (pharmacological cardioversion)
Reported success rates of cardioversion vary:2
- >90% for electrical cardioversion
- 40–70% for pharmacological cardioversion
Evidence regarding the factors that predict successful cardioversion is limited:
- A shorter versus longer duration of AF was independently associated with success in several studies3-6
- Lower body weight4 and pre-treatment with antiarrhythmic drugs5,6 may also be associated with successful cardioversion
- Evidence on the influence of age is conflicting3,6,7
AF recurs within 1 year in approximately half of patients who undergo successful cardioversion.1 Factors that have been identified as potentially predictive of AF recurrence include:3,5,8
- Decreased heart function
- Increased CHA2DS2-VASc score
- Age ≤65 years (rather than older)
- Paroxysmal (rather than permanent) AF
- Alcohol consumption
Ablation
Ablation procedures are performed on patients with AF to attempt to restore a normal sinus rhythm by destroying the cardiac tissue responsible for the arrhythmia:9
- Traditional surgical ablation has reported efficacy rates of >90%; however, this procedure is technically difficult and involves open heart surgery10
- More recently, minimally invasive surgical procedures that make use of energy sources, such as cryoablation and radiofrequency ablation with pulmonary vein isolation, have yielded success rates of up to approximately 80%10
- Catheter ablation, another commonly employed and minimally invasive technique, is reported to be effective in approximately 80% of patients and is now the most popular method11
Guideline recommendations for the management of patients with NVAF
The ESC guidelines for the management of NVAF recommend:12
- Electrical cardioversion for patients who have recent-onset AF and are haemodynamically unstable
- A choice between electrical and pharmacological cardioversion, based on patient and physician preference, in stable patients or those with persistent, symptomatic AF
Percutaneous coronary intervention
PCI with stent implantation is a common coronary revascularization procedure. Approximately 3 million people worldwide undergo PCI each year.13 PCI is required in patients with stable ischaemic heart disease or ACS.13 It is important that patients receive antiplatelet therapy after a PCI to reduce the risk of future ischaemic or atherothrombotic events, particularly stent-related thrombosis, recurrent MI, or cardiovascular death.13 However, the use of antiplatelet therapy increases the risk of bleeding events. For more information on the use of anticoagulants for patients with AF and PCI please see the article ‘Patients with AF Undergoing PCI’.
| Recommendation | Grade of evidence |
|---|---|
| Catheter ablation is recommended in patients with symptomatic paroxysmal AF or persistent AF after one failed or intolerant antiarrhythmic drug who experience symptomatic, recurrent AF on antiarrhythmic drug therapy. This should be performed by an appropriately trained electrophysiologist at an experienced centre | IA |
| Complete electrical isolation of the pulmonary veins is recommended during AF catheter-ablation procedures | IA |
| Catheter ablation of AF should/may be considered as first-line rhythm control therapy to improve symptoms in selected patients with symptomatic paroxysmal AF as an alternative to antiarrhythmic drug therapy, taking into consideration patient choice, benefit and risk | IIB |
Catheter ablation is associated with an approximately 1% risk of stroke or TIA.11 Anticoagulation with a VKA(INR of 2.0 – 3.0) or NOAC ≥3 weeks before ablation may be considered.
Following AF ablation, warfarin or a NOAC should be continued for ≥2 months, and the decision to continue therapy long term is based on the patient’s stroke risk profile. 12
The electrical or pharmacological disruption of left atrium function during the cardioversion procedure is associated with a 5–7% incidence of thromboembolism, including stroke.14 By contrast, the risk is approximately 1% with adequate anticoagulation.15,16
Current guidelines recommend ≥3 weeks of adequate anticoagulation before cardioversion:12,17
- NOACs are recommended, and VKAs can be used if dosed to maintain an INR of 2.0–3.0 12,17
- For patients with AF of <48 hours’ duration and a high risk of stroke, cardioversion can be performed immediately with administration of heparin or a NOAC followed by long-term anticoagulation therapy17
After cardioversion, anticoagulation should be continued long term in patients based on their thromboembolic and bleeding risk profile.12,17
| Recommendation | Grade of evidence |
|---|---|
| In patients with AF undergoing cardioversion, NOACs are recommended with at least similar efficacy and safety to warfarin | IA |
| Effective oral anticoagulation is recommended for ≥3 weeks before cardioversion in all patients with AF | IB |
| For patients with AF of >24-h duration, oral anticoagulant therapy should be continued for ≥4 weeks after cardioversion, (beyond 4 weeks, long-term OAC treatment is determined by the presence of stroke risk factors) | IB |
| In patients at risk of stroke, OAC therapy, whether with dose-adjusted VKA (INR 2.0–3.0) or a NOAC, should be continued long term after cardioversion irrespective of the apparent maintenance of sinus rhythm or ‘first-diagnosis’ characterization of AF | IB |
Results from studies
The ESC guidelines recommend all NOACs for pre- and post-cardioversion anticoagulation therapy.
The use of dabigatran for cardioversion anticoagulation was based on a a subanalysis of the RE-LY trial because a relatively large number of patients planned for cardioversion were included in the study:18
- Outcomes among the 1270 patients who underwent cardioversion were similar to the overall population, and were not significantly different between dabigatran and VKA
Subanalyses of the phase III studies of rivaroxaban (ROCKET AF) and apixaban (ARISTOTLE) also indicated similar outcomes to the overall populations in patients receiving cardioversion, but there were relatively few of these patients in these trials:19,20
- These analyses were limited by their retrospective nature and the lack of TEE data collected at baseline to exclude patients with left atrial/LAA thrombus, in whom cardioversion is contraindicated21
To date, there have been few studies regarding the use of NOACs during AF ablation:
- A single-centre retrospective study and a prospective registry found no difference between dabigatran and warfarin in terms of the periablative risk of bleeding or thromboembolic complications;22,23 however, patients receiving dabigatran took longer to reach the target activated clotting time compared with patients receiving uninterrupted warfarin
- In a post hoc analysis of the phase III ROCKET AF study, outcomes associated with catheter ablation in 79 patients treated with warfarin and rivaroxaban were described;19 the authors noted that long-term outcomes (>30 days) were not statistically different between the treatment groups before and after ablation
Prospective clinical studies have been conducted to prospectively investigate NOAC use in patients undergoing cardioversion and catheter ablation.
The X-VeRT trial of rivaroxaban (NCT01674647) was the first prospective study of a NOAC to report results in the cardioversion setting (N=1504):24
- Following early cardioversion, four rivaroxaban (0.71%) and three VKA (1.08%) patients experienced a primary efficacy event; following delayed cardioversion the numbers were one (0.24%) and two (0.93%), respectively. There was a trend towards lower incidences of thromboembolic events and major bleeding events in favour of rivaroxaban compared with VKA
The ENSURE-AF study (NCT02072434)25 and the EMANATE trial (NCT02100228)26 have reported results ofwith edoxaban and apixaban, respectively.
The ENSURE-AF trial, compared edoxaban 60 mg per day with enoxaparin-warfarin in patients (N=2199) undergoing electrical cardioversion of NVAF.25
- A reduced edoxaban dose of 30 mg once daily was used for patients who had a bodyweight of ≤60 kg or CrCl 15-50 ml/min
- The rates of thromboembolism, as well as major and clinically relevant non-major bleeding was similarly low in both treatment arms, with a net clinical benefit of about 1% both study arms (odds ratio 0.5; 95% CI 0.19-1.25).
In the EMANATE trial, patients (N=1500) with AF undergoing cardioversion were randomizsed to receive apixaban 5 mg twice daily, or heparin/VKA.26
- Reduced apixaban doses of 2.5 mg twice daily were given to patients with two of the following: age ≥ 80 years, weight ≤ 60 kg, or serum creatinine clearance ≥ 133 µmol/Ll.
- Rates of strokes, systemic emboli and, deaths were low for both treatment arms , with 0/753 versus 6/747 strokes (relative risk, [RR] 0; 95% CI 0-0.64; p=0.015); no systemic emboli; and 2 versus 1 deaths (RR=1.98; 95 % CI 0.19-54.00; p>0.999) in the apixaban and heparin/VKA groups, respectively.
- Bleeding rates were low in both treatment arms, with 3/735 versus 6/721 major bleedings (RR=0.49; 95% CI 0.10-2.07; nominal p=0.338) and 11 versus 13 clinically relevant non-major bleeding events (RR=0.83; 95% CI 0.34-1.89; p=0.685) in the apixaban and heparin groups, respectively
It is important to note that these studies, like X-VeRT, were not powered to show significant differences in either safety or efficacy.
The safety of rivaroxaban in patients with AF undergoing catheter ablation was investigated in the open-label VENTURE-AF study (NCT01729871), which was the first prospective, randomized study of a NOAC in this setting:27
- Patients (N=248) with paroxysmal or persistent NVAF received rivaroxaban 20 mg once daily or dose-adjusted VKA (INR 2.0–3.0) before and after ablation
- During the catheter ablation procedure, patients received intravenous heparin
- There was a low incidence of major bleeding and thromboembolic events in both treatment arms, indicating that rivaroxaban is a reasonable alternative to VKA in the setting of catheter ablation
- Based on the design of VENTURE-AF, patients should either:
- Have a TEE and, after confirmed absence of any thrombus, receive rivaroxaban for 1–7 days prior to ablation and for at least 4 weeks afterwards; or
- Take rivaroxaban for at least 3 weeks prior to ablation and for at least 4 weeks afterwards
Since the rivaroxaban study, open-label, prospective studies assessing the safety and efficacy of apixaban (AXAFA-AFNET 5 trial [NCT02227550])28,29 and dabigatran (RE-CIRCUIT trial [NCT02348723])30 have been completed in patients with AF undergoing catheter ablation.
- In the AXAFA-AFNET 5 trial, patients (N=633) with NVAF with a clinical indication for catheter ablation received either continuous apixaban (5 mg twice daily) or a dose- adjusted continuous VKA (INR ≥ 2.0)28
- A reduced apixaban dose of 2.5 mg twice daily was administered if two of more of the following characteristics were present: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine level ≥ 1.5 mg/dl
- Heparin was administered during catheter ablation
- Stroke or TIA occurred in 0.6% and 0% of patients in the apixaban and VKA treatment arms, respectively
- Major bleeding, as defined by International Society on Thrombosis and Haemostasis (ISTH), was reported in 3.1% and 4.4% of patients in the apixaban and VKA treatment arms, respectively
- In the RE-CIRCUIT trial, patients (N= 635) with paroxysmal or persistent NVAF with planned AF ablation received uninterrupted dabigatran (150 mg twice daily) or dose adjusted, uninterrupted warfarin (combination of 1, 3 and 5 mg with target INR of 2.0–3.0)30
- Heparin was also administered during catheter ablation
- The occurrence of major bleeding, as defined by the ISTH, was significantly lower in the dabigatran group versus the warfarin group (1.6% vs 6.9%, respectively; p<0.001)
- From the time of ablation until 8 weeks after the procedure, there were no events of stroke, systemic embolism, or TIA in the dabigatran group, with only one TIA event reported in the warfarin group
The ELIMINATE AF (NCT02942576) trial assessed the safety and efficacy of uninterrupted edoxaban 60 mg once daily (30 mg once daily in patients indicated for a dose reduction) compared with a (VKA) in patients with NVAF undergoing catheter ablation.31
- The occurrence of the primary endpoint (death, stroke or ISTH-defined major bleeding) in the per-protocol population post-ablation (n=417) was 0.3% with edoxaban and 2.0% with VKA treatment
- ISTH-major bleeding was observed in 2.5% of patients in the edoxaban group and 1.5% in the VKA group of the modified intention-to-treat population (n=602). There was one ischaemic and one haemorrhage stroke in the edoxaban group
For a summary of clinical trials that explored the use of NOACs in patients with NVAF undergoing PCI please see the article ‘Patients with AF Undergoing PCI’.
References
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See Also
Peripheral Artery Disease: causes and consequences
See Also
Coronary Artery Disease: causes and consequences
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