Novel Oral Anti-Coagulants (NOACs): Hot Topics & Current Issues

Roundtable Discussion

SESSION 6: NOAC treatment in chronic renal impairment


Jean-Yves Le Heuzey
Professor of Cardiology and Head of the Arrhythmia Department
Georges Pompidou Hospital, Paris, France


A. John Camm, London, UK

Marco Alings, Breda, The Netherlands
Raffaele de Caterina, Chieti, Italy
Paulus Kirchhof, Birmingham, UK
Freek Verheugt, Amsterdam, The Netherlands

Written By Katrina Mountfort, Medical Writer, Radcliffe Cardiology
Reviewers - John Camm, Marco Alings, Raffaele De Caterina, Paulus Kirchhof, Jean-Yves Le Heuzey, Freek W A Verheugt

Professor Le Heuzey started by describing the absorption and metabolism of NOACs. All NOACs are partially eliminated by the kidneys. The renal elimination of NOACs varies considerably: dabigatran 80%, apixaban 25 %, rivaroxaban 35 % and edoxaban 50 %, and therefore different NOACs have different levels of contraindications.42 Practical recommendations have been proposed for the use of NOACs in chronic kidney disease (see Table 2); dabigatran is contraindicated if creatinine clearance (CrCl) is lower than 30 ml/min, apixaban and rivaroxaban if lower than 15 ml/min (no data available for edoxaban at time of recording).1,2 Bioavailability also differs according to the drug: for dabigatran, 3–7 %; for edoxaban 50 %, for edoxaban 62 %, and for rivaroxaban 66–100 %. Therefore, different dosages are recommended in suboptimal renal function. The age of the patient should also be taken into account because elderly patients often have decreased renal clearance.

Guidance is also available regarding when to stop NOACs before a planned surgical intervention. The duration of action of the drug is directly related to CrCl: with a normal renal clearance NOACs can be stopped 24–48 hours before a planned surgical intervention, but for example with a CrCl of 30-50 ml/min, the effect of dabigatran can persist for up to 96 h. The risk of bleeding associated with the intervention should of course also be taken into account. The proposal of EHRA is that renal function should be monitored regularly in patients taking NOACs and the dose adapted accordingly. Renal function should be monitored at the following intervals in patients with chronic kidney disease: yearly with a CrCl ≥60 ml/min; 6-monthly for elderly (>75 years) or frail patients on dabigatran (CrCl 30–60 ml/min); and 3 monthly when CrCl ≤30 ml/min.

In the panel discussion, Professor De Caterina considered that NOAC therapy should not be used in patients with CrCl ≤30 ml/min. A traffic light analogy was suggested for advising doctors, with a red light at CrCl ≤30 ml/min, yellow at 30–50 ml/min and green ≥ 50 ml/min. However, following the availability of drugs with lower renal clearance, this might change in the future, especially if dosages are carefully tailored to the individual.

NOACs Renal Dysfunction

At adjusted dosages, the NOACs have shown preserved efficacy in patients with impaired renal function, whereas there is little evidence for the efficacy of warfarin in these patients. The choice of drug should be influenced by renal function; while some panel members still prescribe warfarin to patients with CrCl 30–50 ml/min, all concede that NOACs might be preferable. Regular CrCl monitoring is essential. The panellists consider that ‘NOAC outpatient-clinics’ in some countries are well equipped to handle the treatment decisions, follow-up and paperwork involved with prescribing NOACs, not only in patients with renal impairment. Despite these restrictions, in most phase III trials, patients with renal impairment derived considerable benefit from NOACs. In conclusion, as far as renal function is concerned with regards to NOACs, renal function must be known before choosing a drug, before choosing the dose, in follow-up because renal function will change, and when planning, e.g. a surgical intervention. Renal function is important with regards to patients taking NOACs.

For a full written summary of discussions please click here:

A. John Camm, Professor of Clinical Cardiology and Head of the Department of Cardiac and Vascular Sciences, St. George's Hospital Medical Centre, London, UK
Marco Alings, Director of the Cardiology Training Program, Amphia Ziekenhuis, Breda, The Netherlands
Raffaele De Caterina, Professor of Cardiology and Director of the University Cardiology Division, "G. d'Annunzio" University, Chieti, Italy
Paulus Kirchhof, Chair in Cardiovascular Medicine Cardiovascular and Respiratory Sciences, University of Birmingham, UK
Jean-Yves Le Heuzey, Professor of Cardiology and Head of the Arrhythmia Department, Georges Pompidou Hospital, Paris, France
Freek Verheugt, Chairman, Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands

Professor Camm has disclosed the following financial relationships:
Consultant/Advisor/Speaker: Actelion, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Biotronik, BMS, ChanRX, Daiichi Sankyo, Gilead, GSK, InfoBionic, Incarda, Johnson and Johnson, Medtronic, Menarini, Merck, Mitsubishi, Novartis, Otsuka, Pfizer, Sanofi, Servier, St. Jude Medical, Takeda, Xention

Doctor Alings has disclosed the following financial relationships:
Consultant/Advisor: Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo

Professor De Caterina has disclosed the following financial relationships:
Research grants: Boehringer Ingelheim
Consultant/Advisor/Speaker: Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Novartis

Professor Kirchhof has disclosed the following financial relationships:
Research grants: BMS/Pfizer, Cardiovascular Therapeutics, Daiichi Sankyo, Sanofi, St. Jude Medical.
Consultant/Advisor/Speaker: Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Johnson & Johnson, Medtronic, MSD, Pfizer, Servier

Professor Le Heuzey has disclosed the following financial relationships:
Consultant/Advisor: Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sanyo

Professor Verheugt has disclosed the following financial relationships:
Consultant/Advisor: Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo

The assigned learning objectives for this roundtable are listed for your information:
  • To review the established evidence-base for non-VKA thromboprophylaxis in atrial fibrillation (AF)
  • To consider recent and emerging data on non-VKA oral anticoagulants in AF trials and registries
  • To discuss on-going non-VKA oral anticoagulant research in patients with AF
  • To identify and refine the indications for specific non-VKA oral anticoagulants in AF
  • To establish the nature of further non-VKA oral anticoagulant research needed for new AF indications

This educational activity is intended for an international audience of non-US healthcare professionals, specifically electrophysiologists and cardiologists. However, neurologists, internal medicine specialists, primary care physicians, and other healthcare professionals involved in the diagnosis and management of patients with atrial fibrillation (AF) will also find this topical.

This course is accredited by the European Board for Accreditation in Cardiology (EBAC) for 1 CME credit hour. The CME e-learning modules can be accessed here.

CME-CPD AcademyThe CME element of this educational module has been managed by Siyemi Learning and is powered by CME-CPD Academy.

The Novel Oral Anti-Coagulants (NOACs): Hot Topics & Current Issues roundtable was supported by an unrestricted educational grant by Daiichi-Sankyo.