Comments on the Spanish Society of Cardiology Critical Review of the ESC 2010 Clinical Practice Guidelines on Atrial Fibrillation

To the Editor,

The critique by Anguita et al.¹ perpetuates many misconceptions. Many reported risk factors for stroke in atrial fibrillation (AF) were derived from the non-warfarin arms of trial cohorts but in the historical trials, females were under-represented, many risk factors were not systematically recorded or not uniformly defined and <10% of those screened were ultimately randomised. Thus, additional data are needed from epidemiological and cohort studies. Numerous studies have now shown how the risk of stroke rises from age >65 and that vascular disease also increases the risk of stroke and/or death in AF². Females have a disproportionate risk of stroke when AF develops, and various studies support the inclusion of female gender as a stroke risk factor². More contemporary studies do suggest that uncontrolled hypertension is more of a risk, rather than well-controlled blood pressure. After all, any (single) stroke risk factor will confer a risk of stroke when present with AF.

The previous artificial division into low/moderate/high stroke risk strata evolved so that we could pick out the ‘high risk’ category to subject these patients to an inconvenient drug, warfarin. With the availability of new oral anticoagulants (OAC), the 2010 ESC guideline focuses more on improving our identification of ‘truly low risk’ patients, de-emphasises the (artificial) low/moderate/high risk stratification approach and recommended the use of a risk factor based approach with the CHA₂DS₂-VASc score. Since the original validation study, other independent validation studies have been published for CHA₂DS₂-VASc². The advantage of CHA₂DS₂-VASc, which is more inclusive of common stroke risk factors, is that it consistently identifies ‘truly low risk’ patients who do not need any antithrombotic therapy, whilst those with ≥1 stroke risk factors can be considered for effective stroke prevention therapy, which is essentially OAC with either (very) well controlled warfarin or one of the new agents. Certainly, CHA₂DS₂-VASc is as good as–and possibly better–than scores such as CHADS₂ in identifying patients who develop stroke.

The ESC guideline already clearly recommends that antithrombotic therapy is necessary in all patients with AF unless they are ‘age <65 and low risk’, and and thus, young women who essentially have no risk factors (i.e. lone AF) would fall into this category. As a consequence, patients with ‘female gender’ only as a single risk factor (but still a CHA₂DS₂-VASc score=1 on that basis) would not need anticoagulation, if they fulfil the criteria of ‘age <65 and lone AF’.

Anguita et al.¹ take issue with the recommendation that AF patients with stable vascular disease can be managed with OAC monotherapy. The addition of aspirin to OAC substantially increases the risk of major bleeding and results in a 2.4-fold increase in intracranial haemorrhage. Thus, long term combination therapy would probably outweigh the potential (multifactorial) risk of late stent thrombosis.

Anguita et al.¹ suggest the dronedarone was recommended for use in permanent AF, which is incorrect. Both the ESC and the American guidelines provide near identical recommendations relating to the use of dronedarone for reduction of hospitalizations (Class IIa, LoE B) and it directly follows from its regulatory approval. Dronedarone was also given a recommendation as an antiarrhythmic agent for patients with AF on the basis of consistent although modest antiarrhythmic effects. The alphabetically-arranged positioning of dronedarone in ESC guideline flowcharts does not imply that it is superior to other antiarrhythmics within the same category.

Anguita et al.¹ also argue that the ESC guideline picks out hypertension with LV hypertrophy as a distinct pathology to be considered when choosing an antiarrhythmic agent. This was entirely in line with previous and current guidelines except for the Canadian guidelines which chose a range of left ventricular ejection fractions to guide antiarrhythmic drug choice.

Post approval pharmacovigilance data suggested that dronedarone may be associated with hepatotoxicity. One trial found an increase in all-cause mortality, stroke rate and cardiovascular hospitalizations, particularly for heart failure, associated with dronedarone treatment in permanent AF. The ESC has kept in close touch with developments and would re-consider its AF guidelines with a focussed update as soon as feasible.

The full text of this article is available only as supplementary material.

Conflict of interest

Both authors were members of the Task Force for the 2010 ESC guidelines on atrial fibrillation, and Prof. Camm acted as Chair of the Task Force.

Prof. Lip has served as a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Biotronik, Portola and Boehringer Ingelheim and has been on the speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, and Sanofi Aventis.

Prof. Camm has served as a consultant and has been on the speakers bureau for various pharmaceutical companies, and was a member of the steering committee for the PALLAS trial.

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Supplementary material

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.rec.2011.12.008.

Appendix A. Supplementary data

The full text of this article is available only as supplementary material.

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