Br J Cardiol 2018;25(suppl 1):S3–S5doi:10.5837/bjc.2018.s01
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Sponsorship Statement:

Bayer plc. commissioned and funded this supplement. The company has reviewed the data to ensure factual accuracy in relation to Bayer products and compliance with industry guidelines. Rivaroxaban prescribing information current at the time of publication is available here.

Job code: UKXAR04170195a, Date of preparation: July 2018

For notes on dosing recommendations from Xarelto® ▼ (rivaroxaban) SmPC (Summary of Product Characteristics) please see the box at the foot of this page

Patients with atrial fibrillation are at an increased risk for ischaemic stroke and require long-term prophylaxis with an anticoagulant. Ablation and direct current cardioversion are commonly performed in patients with atrial fibrillation. These procedures additionally predispose patients to thrombotic events and peri-procedural anticoagulation is also indicated.

Until recently, warfarin was the drug of choice for patients with atrial fibrillation. Data from the ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation),1 ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation),2 RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy)3 and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)4 trials demonstrated non-inferior or superior reduction in stroke/systemic embolism with rivaroxaban, apixaban, dabigatran and edoxaban, respectively, compared with vitamin K anatgonsist (VKA) therapy. Due to this evidence, clinical guideline committees now recommend administration of VKAs, rivaroxaban, apixaban, dabigatran or edoxaban for prophylaxis against ischaemic stroke in patients with non-valvular atrial fibrillation (NVAF).5-10


Non-vitamin K antagonist oral anticoagulants’ (NOACs’) role in atrial fibrillation additionally includes peri-procedural anticoagulation in electrophysiological procedures. The X-VeRT (Explore the Efficacy and Safety of Once-daily Oral Rivaroxaban for the Prevention of Cardiovascular Events in Subjects With Nonvalvular Atrial Fibrillation Scheduled for Cardioversion)11 and ENSURE-AF (Edoxaban Versus Enoxaparin–Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation)12 trials demonstrated the efficacy and safety profile of rivaroxaban and edoxaban in patients undergoing direct current cardioversion. More recently, the results of the EMANATE (Eliquis Evaluated in Acute Cardioversion Compared to Usual Treatments for Anticoagulation in Subjects with nonvalvular AF) trial support the use of apixaban in patients with AF undergoing cardioversion.13

In patients undergoing catheter ablation of atrial fibrillation, the first completed study with a NOAC, VENTURE-AF (Uninterrupted Rivaroxaban vs Uninterrupted Vitamin K Antagonists for Catheter Ablation in Non-valvular Atrial Fibrillation), showed the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy.14 Recent evidence from the RE-CIRCUIT (Randomised Evaluation of Dabigatran Etexilate Compared to Warfarin in Pulmonary Vein Ablation: Assessment of an Uninterrupted Periprocedural Anticoagulation Strategy)15 trial demonstrated significant reduction in major bleeding with the peri-procedural administration of dabigatran compared with standard VKA.

Patients with atrial fibrillation who undergo percutaneous coronary intervention (PCI) are particularly difficult to manage. Clinical practice guidelines recommend that patients undergoing stent replacement receive dual antiplatelet therapy (DAPT), which includes aspirin and a P2Y12 inhibitor.16,17 The recommended duration of DAPT differs according to the type of stent that is used. For example, patients with stable ischaemic heart disease that receive a bare metal stent are recommended to receive DAPT for at least one month and those that receive a drug-eluting stent are recommended to receive DAPT for at least six months.18 Triple combination therapy, which includes an oral anticoagulant and DAPT, is recommended in patients with both acute coronary syndrome (ACS) and atrial fibrillation.6,7,10 It has been estimated that 2–21% of patients with ACS also have atrial fibrillation.7,19 This combination regimen is associated with a three- to four-fold increased risk of fatal and non-fatal bleeding due to intensified antithrombotic effect.20-24 Administration of anticoagulant in conjunction with antiplatelet therapy aims to reduce the occurrence of ischaemic events and to minimise the risk of bleeding complications.20,22–25

The PIONEER AF-PCI (Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with Atrial Fibrillation who Undergo Percutaneous Coronary Intervention) trial was an open-label, randomised, controlled multi-centre trial that evaluated the safety of two different regimens of rivaroxaban compared with VKA in patients with NVAF who underwent PCI with stent placement. PIONEER AF-PCI was a safety study. The primary safety end point was the occurrence of clinically significant bleeding. This end point was a composite of Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding or bleeding requiring medical attention (BRMA), and was evaluated throughout the 12-month treatment period.26

More recently, results from the RE-DUAL PCI (the Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran vs. Triple Therapy with Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) study have also been announced, which have further added to the evidence base in this area.27

This supplement summarises the findings of the PIONEER AF-PCI trial and a subsequent post-hoc analysis assessing all-cause death or rehospitalisation as a composite end point. We provide a commentary on the role of rivaroxaban in the UK and provide a perspective on the future of NOACs in peri-procedural ablation of atrial fibrillation and direct current cardioversion.

Conflict of interest

The PERFUSE Study Group has received research grant funding from JnJ.


Articles in this supplement include:

Anticoagulation in patients with non-valvular AF undergoing PCI: clinical evidence from PIONEER AF-PCI
The PIONEER AF-PCI study: its implications for everyday practice in the UK
The potential for NOACs in cardiac ablation in the UK
Use of NOAC drugs in DC cardioversion for patients with non-valvular AF



1. Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91.

2. Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981–92.

3. Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–51.

4. Giugliano RP, Ruff CT, Braunwald E, et al. for the ENGAGE AF-TIMI 48 investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-104.

5. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–962.

6. European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ et al. 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 2010;31:2369–429.

7. January CT, Wann LS, Alpert JS et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64:e1–e76.

8. Macle L, Cairns J, Leblanc K et al. 2016 focused update of the Canadian Cardiovascular Society guidelines for the management of atrial fibrillation. Can J Cardiol 2016;32:1170–85.

9. Verma A, Cairns JA, Mitchell LB et al. 2014 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation. Can J Cardiol 2014;30:1114–30.

10. You JJ, Singer DE, Howard PA et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 suppl):e531S–e575S.

11. Cappato R, Ezekowitz MD, Klein AL et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014;35:3346–55.

12. Goette A, Merino JL, Ezekowitz MD et al. Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial. Lancet 2016;388:1995–2003.

13. Ezekowitz MD. Apixaban vs conventional therapy in anticoagulation-naïve patients with atrial fibrillation undergoing cardioversion: the EMANATE trial. Presented at European Society of Cardiology congress (Hot Line: late-breaking clinical trials session, 28th August 2017), Barcelona, Spain.

14. Cappato R, Marchilinski FE, Hohnloser SH et al. for the VENTURE-AF investigators. Uninterrupted rivaroxaban vs uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J 2105;36:1805–11.

15. Calkins H, Willems S, Gerstenfeld EP et al. Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation. N Engl J Med 2017;376:1627–36.

16. Windecker S, Kolh P, Alfonso F et al. 2014 ESC/EACTS guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35:2541–619.

17. Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:e574–e651.

18. Levine GN, Bates ER, Bittl JA et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. An update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation 2016;134:e123–e155.

19. Schmitt J, Duray G, Gersh BJ, Hohnloser SH. Atrial fibrillation in acute myocardial infarction: a systematic review of the incidence, clinical features and prognostic implications. Eur Heart J 2009;30:1038–45.

20. Faxon DP, Eikelboom JW, Berger PB et al. Consensus document: antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting. A North-American perspective. Thromb Haemost 2011;106:572–84.

21. Hansen ML, Sorensen R, Clausen MT et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010;170:1433–41.

22. Huber K, Airaksinen KJ, Cuisset T, Marin F, Rubboli A, Lip GY. Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: similarities and dissimilarities between North America and Europe. Thromb Haemost 2011;106:569–71.

23. Lamberts M, Gislason GH, Olesen JB et al. Oral anticoagulation and antiplatelets in atrial fibrillation patients after myocardial infarction and coronary intervention. J Am Coll Cardiol 2013;62:981–9.

24. Lip GY, Huber K, Andreotti F et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Thromb Haemost 2010;103:13–28.

25. Hemmrich M, Peterson ED, Thomitzek K, Weitz JI. Spotlight on unmet needs in stroke prevention: the PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials. Thromb Haemost 2016;116(suppl 2):S33–S40.

26. Gibson CM, Mehran R, Bode C et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 2016;375:2423–34.

27. Cannon CP, Bhatt DL, Oldgren J et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 2017;377:1513–24.


Notes on dosing recommendations from Xarelto® ▼ (rivaroxaban) SmPC (Summary of Product Characteristics)

For the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors, the recommended dose is 20 mg once daily (15 mg once daily in patients with moderate [creatine clearance {CrCl} 30-49 ml/min] or severe [CrCl 15-29 ml/min] renal impairment). To be used with caution in severe renal impairment and use is not recommended in patients with CrCl <15 ml/min.

The above doses were studied in the pivotal ROCKET AF study in patients with non-valvular AF.

In the PIONEER AF-PCI study, participants with non-valvular AF who had undergone percutaneous coronary intervention (PCI) with stenting were randomly assigned to receive either rivaroxaban 15 mg once daily (10 mg once daily, CrCl 30-50 ml/min) plus a P2Y12 inhibitor for 12 months, or rivaroxaban 2.5 mg twice daily plus dual antiplatelet therapy (DAPT) for one, six, or 12 months, or dose-adjusted vitamin K antagonist once daily plus DAPT for one, six, or 12 months.

The Xarelto® (rivaroxaban) SmPC has been updated under ‘Special populations’ in the section on ‘Posology and method of administration’ following completion of the PIONEER AF-PCI study; the rivaroxaban 15 mg once daily regimen, but not the 2.5 mg twice daily regimen, has been included.

In summary, the SmPC update states that for patients with non-valvular AF who require oral anticoagulation and undergo PCI with stent placement, there is limited experience of a reduced dose of rivaroxaban 15 mg once daily (10 mg once daily, CrCl 30-49 ml/min) in addition to a P2Y12 inhibitor for a maximum of 12 months.

Disclaimer: Medinews Cardiology Limited advises healthcare professionals to consult up-to-date Prescribing Information and the full Summary of Product Characteristics available from the manufacturers before prescribing any product. Medinews Cardiology Limited cannot accept responsibility for any errors in prescribing which may occur.