Article

How to Choose Between NOACs

Abstract

On 12 November 2014, Radcliffe Cardiology, in association with Arrhythmia & Electrophysiology Review (AER) journal, held a roundtable discussion in London, UK. The discussion held between an expert group of physicians was moderated by Professor A John Camm, a renowned authority in anticoagulation and atrial fibrillation. The meeting comprised a series of seven presentations and subsequent panel discussions on a range of topical issues related to the use of non-vitamin K antagonist (novel) oral anticoagulants (NOACs): real-world versus clinical trial data; once or twice daily dosing regimens; spot checks or monitoring for anticoagulation status; antidotes for NOACs; NOACs and dual antiplatelet therapy; NOAC treatment in chronic renal impairment; and choosing between NOACs. This paper summarises the presentations and presents key highlights from the subsequent discussions.

Disclosure: Professor Camm is a consultant/advisor/speaker for 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 and Xention; Doctor Alings is a consultant/advisor for Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo; Professor De Caterina has received a research grant from Boehringer Ingelheim, and is a consultant/advisor/speaker for Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Novartis; Professor Kirchhof has received research grants from BMS/Pfizer, Cardiovascular Therapeutics, Daiichi Sankyo, Sanofi, St. Jude Medical, and is consultant/advisor/speaker for Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Johnson & Johnson, Medtronic, MSD, Pfizer and Servier; Professor Le Heuzey is a consultant/advisor for Bayer, Boehringer Ingelheim, BMS/Pfizer and Daiichi Sanyo; Professor Verheugt is consultant/advisor for Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo

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Citation:Arrhythmia & Electrophysiology Review 2015;4(1 Suppl 1):8-9

Support: The roundtable was supported by an unrestricted educational grant from Daiichi-Sankyo.

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In order to choose between NOACs, Dr Alings started by highlighting the differences between the guidelines: the ESC AF guidelines discuss when NOACs should be used1 and in addition, the EHRA practical guide suggests how the anticoagulation should be achieved with NOACs.2 According to the ESC guidelines, a CHA2DS2VASc ≥1 indicates the use of an OAC. Several factors may influence treatment choice. The renal clearance varies considerably among the NOACs. In clinical trials of NOACs compared with VKAs, drugs were dose adjusted according to renal function.

Acknowledging differences between clinical trials, in over 70,000 patients studied, all NOACs proved non-inferior to warfarin, and some were found to be superior for prevention of stroke and bleeding.8–11 In terms of stroke risk, the risk of haemorrhagic stroke accounts for the reduced risk observed in these trials. In terms of bleeding risk, ENGAGE, ARISTOTLE and RE-LY (at the lower dose) showed significantly reduced risk of major bleeding compared with warfarin. To summarise the impressive results of the NOAC trials: major reductions in intracranial bleeding were seen compared with warfarin, with RE-LY, ARISTOTLE and ENGAGE being associated with the greatest mortality benefits.

In conclusion, where OACs are indicated, NOACs should be considered rather than dose-adjusted VKA. The choice of NOAC may be influenced by concomitant disease, such as renal function and a prior gastrointestinal bleed, and concomitant drugs (e.g. P-glycoprotein inhibitors). In patients with a low bleeding risk, it is probably best to select the NOAC with the best reduction in ischaemic stroke. In patients with a high bleeding risk, the NOAC with the best reduction in major bleeding compared with VKA is probably the best option. Patient preference to once daily versus twice daily regimens may also influence the choice of NOAC. Finally, regional or national availability and reimbursement of the individual agents may affect treatment choice.

The panel discussion emphasised the fact that the methodologies of the NOAC clinical trials differed, and are therefore not directly comparable. However, the outcomes were highly consistent across trials. Professor Kirchhof stated that meta-analyses of these trials have found remarkable similarities in reduction in intracranial haemorrhage, mortality benefits and reduction in major bleeding. However, statistical significance depends on the number of events observed, rather than the compound studied; this is important when extrapolating clinical trial results to different patient populations. In terms of efficacy, valid comparisons cannot be made between NOACs given the available data. Factors such as pharmacokinetics, dosage frequency and capsule size are much more important in clinical practice when making the choice for a NOAC. Professor Le Heuzey suggested that the bleeding risk is useful in selecting the best NOAC for a patient but cannot be easily predicted. For many general practitioners, detailed knowledge of each NOAC is not necessary; the best drug might be the one with which they have most experience and they should not try to differentiate. Professor De Caterina reminded the panel that efficacy and safety should not be considered in isolation: the compound parameter of efficacy and safety, the net clinical benefit, is an important evaluation. He highlighted the fact that, in order to optimise treatment, it is important to remember that not all risks have the same prognostic implication, but, for example, haemorrhagic stroke has a worse prognosis than ischaemic stroke. The only way to determine the optimum NOAC is to perform a head-to-head-comparison but is questionable whether this is feasible. The panel concluded that at this moment each patient should be assessed on a case-by-case basis, carefully looking at the risk factors.

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