Gaps in Evidence
Regarding recent developments for glucose-lowering therapies, the presence of AF at baseline or during follow-up is mostly not systematically reported and information on whether strokes are AF-related is mostly lacking. These drugs, SGLT2 inhibitors in particular, have beneficial effects on the incidence of HF and CKD. Whether a reduction in the incidence of AF accompanies a proportional reduction of the risk of stroke in patients with DM is less well explored.
The beneficial effects of SGLT2 inhibitors in HFrEF patients have been clearly documented in patients with diabetes. However, their impact on outcome in these patients with both diabetes and AF at baseline is less clear. Thus, more dedicated analyses on the effects of SGTL2 inhibitors in diabetic HFrEF patients with AF and their potential differential impact in patients with HFrEF and HFpEF and concomitant AF and diabetes are needed.
DM (other than a dichotomous variable) and the characteristics of DM including diabetes sub-classification and the level of glycaemic control were not systematically reported in studies on stroke reduction in AF patients treated with DOACs. Accordingly, the relation between the severity of DM, the level of glycaemic control, and AF-related outcomes is not well documented.
Diabetes mellitus is associated with an increased risk of deterioration of renal function. Both DM and CKD increase the risk of stroke and other CV complications. Yet, patients with significantly impaired renal function (CrCl < 30 mL/min) were largely excluded from the DOAC trials. The use of a reduced dose of rivaroxaban, apixaban, or edoxaban is recommended in patients with a CrCl between 15 and 30 mL/min, but patients with a CrCl <25–30 mL/min were not included from the randomized trials. The FDA approved a low 75 mg b.i.d. dose of dabigatran for patients with a CrCl <30 mL/min, available in the USA, but it has not been tested in a prospective trial, and it is not approved for use within Europe.
In patients with AF and acute coronary syndrome, current treatment is based on anticoagulants plus anti-platelets (single or dual) for up to 1 year after the acute event. The general recommendation after 12 months is to omit antiplatelet drugs and prescribe only oral anticoagulants. In view of the complexity of the coronary pattern in ischaemic heart disease and the role of DM in modulating its evolution, more data are needed in order to assess if specific subgroups (including diabetic patients) of patients with AF, CAD and a previous acute event could benefit from the combination of oral anticoagulants and anti-platelets for longer a period.
The incremental risk of stroke and major bleeding in patients with AF and also DM is not fully understood. Sub-analyses of the randomized trials show that in some diabetic patients had more (i.e. RELY, ARISTOTLE), and in some fewer (ROCKET, ENGAGE) residual stroke risk factors according to the CHADS2 or CHA2DS2-VASc scores. A similar large variation in residual stroke risk can be appreciated in real-world observational studies.
The potential beneficial effect of DOACs on the development of AF (or AF recurrences/progression) and diabetes have been hypothesized and are supported by data from both basic science and observational clinical studies, but a formal assessment in RCTs is needed.
The authors thank the EHRA Scientific Document Committee: Dr Nikolaos Dagres, Prof. Thomas Deneke, Prof. Arthur Wilde, Prof. Frank R. Heinzel, Prof. Christian Meyer, Prof. Lucas Boersma, Prof. Radoslaw Lenarczyk, Prof. Luigi di Biase, Dr Elena Arbelo, Dr Avi Sabbag, Prof. Pierre Jais, Prof. Milos Taborsky, and Asso. Prof. Markus Stühlinger.
Europace. 2021;23(12):1873-1891. © 2021 Oxford University Press
Copyright 2007 European Heart Rhythm Association of the European Society of Cardiology (ESC). Published by Oxford University Press. All rights reserved.