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 aims to re-establish a normal sinus rhythm in patients with AF, either by:

  • '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 studies
  • Lower body weight and pre-treatment with antiarrhythmic drugs may also be associated with successful cardioversion
  • Evidence on the influence of age is conflicting

AF recurs within 1 year in approximately half of patients who undergo successful cardioversion. Factors that have been identified as potentially predictive of AF recurrence include:

  • Decreased heart function
  • Increased CHA2DS2-VASc score
  • Age ≤65 years (rather than older)
  • Paroxysmal (rather than permanent) AF
  • Alcohol consumption


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:

  • Traditional surgical ablation has reported efficacy rates of >90%; however, this procedure is technically difficult and involves open heart surgery
  • 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%
  • 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 method

Guideline recommendations for the management of patients with NVAF

The ESC guidelines for the management of NVAF recommend:

  • 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 AF

Percutaneous coronary intervention

PCI with stent implantation is a common coronary revascularization procedure. Approximately 3 million people worldwide undergo PCI each year. PCI is required in patients with stable ischaemic heart disease or ACS. 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. However, the use of antiplatelet therapy increases the risk of bleeding events.

Guideline recommendations for the management of patients with AF undergoing PCI

The ESC guidelines for the management of patients with AF undergoing PCI recommend the following:

For patients at high risk of bleeding, the ESC guidelines has put forward two recommended treatment courses upon hospital discharge:

  • The use of dual therapy (OAC plus clopidogrel) for up to 12 months post PCI, followed by long-term OAC monotherapy from 12 months


  • The use of triple therapy (OAC plus clopidogrel plus aspirin) for 1 month followed by dual therapy (OAC plus clopidogrel) up to 12 months, with long-term treatment using OAC monotherapy from 12 months

In cases where the patient’s ischaemic risk outweighs the risk of bleeding, the ESC guidelines recommend the following treatment action:

  • Triple therapy (OAC plus clopidogrel plus aspirin) for 1 month and up to 6 months, followed by dual therapy (OAC plus clopidogrel or aspirin) for 6 months up to 1-year post PCI
  • Long-term treatment with OAC monotherapy is recommended from 1-year post PCI

European Society of Cardiology recommendations for cardioversion of recent-onset AF
European Society of Cardiology recommendations for cardioversion of recent-onset AF

ESC recommendations for atrial ablation
Recommendation Grade of evidence
Catheter ablation is recommended in patients with symptomatic paroxysmal AF who experience symptomatic, recurrent AF on antiarrhythmic drug therapy and who instead prefer further rhythm-control therapy. This should be performed by an appropriately trained electrophysiologist at an experienced centre IA
Catheter ablation of AF should target isolation of the pulmonary veins IIA
Catheter ablation of AF should be considered as first-line therapy 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. Anticoagulation with a VKA(INR of 2.0 – 3.0) or NOAC should be considered when catheter ablation is planned. Anticoagulation with a NOAC is an alternative to warfarin.

The electrical or pharmacological disruption of left atrium function during the cardioversion procedure is associated with a 5–7% incidence of thromboembolism, including stroke. By contrast, the risk is approximately 1% with adequate anticoagulation.

Current guidelines recommend ≥3 weeks of adequate anticoagulation before cardioversion:,

  • Either with a VKA, dosed to maintain an INR of 2.0–3.0, or a NOAC
  • Unless a TEE excludes left atrial or LAA thrombus, in which case cardioversion can be performed immediately with heparin anticoagulation

After cardioversion, anticoagulation with a VKA or a NOAC should be given for ≥4 weeks and may need to be continued indefinitely in some patients.

ESC recommendations for anticoagulation in patients with NVAF undergoing cardioversion
Recommendation Grade of evidence
For patients with AF of ≥48 h duration, or when the duration of AF is unknown, oral anticoagulant therapy (e.g. VKA with INR 2.0–3.0 or dabigatran) is recommended for ≥3 weeks prior to and for ≥4 weeks after cardioversion, regardless of the method (electrical or oral/intravenous pharmacological) IB
In patients with risk factors for stroke or AF recurrence, oral anticoagulant therapy, whether with dose-adjusted VKA (INR 2.0–3.0) or a NOAC, should be continued lifelong irrespective of the apparent maintenance of sinus rhythm following cardioversion IB

Result from studies

The ESC guidelines recommend dabigatran for pre-cardioversion anticoagulation based on a subanalysis of the RE-LY trial because a relatively large number of patients planned for cardioversion were included in the study:

  • 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:

  • 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 contraindicated

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; 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; 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):

  • 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) and the EMANATE trial (NCT02100228) 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.

  • 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.

  • 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:

  • 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]) and dabigatran (RE-CIRCUIT trial [NCT02348723])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)
    • 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)
    • 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 aimed to assess 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, with an expected completion date of November 2018.

Trials that explored the use of NOACs in patients with NVAF undergoing PCI have also been conducted.
The PIONEER AF-PCI (NCT01830543) trial, an open-label, randomized, controlled, multi-centre study, explored two treatment strategies of Rivaroxaban and a dose-adjusted oral VKA treatment in patients with NVAF who underwent PCI.

  • Patients (N=2124) received rivaroxaban 15 mg once daily plus a P2Y12 inhibitor, rivaroxaban 2.5 mg twice daily plus DAPT, or standard therapy (warfarin plus DAPT)
  • The rate of clinically significant bleeding was significantly lower in both rivaroxaban arms compared with the VKA plus DAPT arm (p<0.001 for both groups)
  • Recurrent hospitalization and all-cause mortality rates were also lower in the rivaroxaban 2.5 mg twice daily arms compared with the VKA plus DAPT arm, with incident rates of 31.9% versus 41.9% respectively (hazard ratio 0.75; 95% CI, 0.62-0.90; p=0.002)
  • Rates of cardiovascular events (MI, stroke or death from cardiovascular causes) were similar across the three treatment groups; however, this study was not powered to measure efficacy

The RE-DUAL PCI trial, compared triple therapy (warfarin plus P2Y12 inhibitor and ASA) with a dual therapy (110 mg or 150 mg dabigatran plus P2Y12 inhibitor) regimens in patients with AF who had undergone PCI.

  • Rates of non-major bleeding events were lower in the dual therapy arms compared with the triple therapy arm (both dual therapy arms demonstrated p<0.001 for non-inferiority; p<0.001 for superiority in the dabigatran 110 mg group only)
  • Rates of thromboembolic events, death or unplanned revascularization were similar for the combined dual therapy arms and the triple therapy group (p=0.005 for non-inferiority)
  • Triple therapy with warfarin was associated with a higher rate of bleeding events compared with dabigatran plus a P2Y12 inhibitor (110 mg and 150 mg doses), with similar thromboembolic event rates

Next section: Other Options

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