Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial☆
Introduction
Atrial fibrillation (AF) is the most common sustained arrhythmia and a major risk factor for stroke [1]. Patients with AF have a five-fold increased risk of stroke compared to patients without AF [1]; however, patients' absolute risk is modulated by age and the presence of cardiovascular conditions. DM is one of the most frequent comorbidities among patients with AF [2], [3] and cohort studies demonstrate that the presence of DM is associated with an increased risk of developing AF [4], [5]. Multiple studies have identified DM as a strong independent predictor for stroke among AF patients [6] and as a result, DM is an important component of all major AF-stroke risk stratification schemes, such as CHA2DS2-VASC [7], [8]. Using these schemes, current guidelines recommend the use of oral anticoagulation therapy for all AF patients with DM [9], [10]. DM is not only an independent risk factor for stroke [11], but diabetics who suffer stroke have more severe residual disability [12] and an increased long-term mortality compared to non-diabetic patients [11]. The risk of death following stroke is two-fold higher in patients with DM within the first year and only 20% of these patients survive beyond 5 years [13].
Oral anticoagulation is highly effective at preventing stroke due to AF. Compared to no therapy, adjusted-dose warfarin reduces stroke by 64% [14] and novel oral anticoagulants (NOACs), including dabigatran, reduce stroke or systemic embolism risk by an additional 20% compared to warfarin [15], [16]. The aim of this subgroup analysis of RE-LY trial [17], [18] is to investigate the efficacy and safety of dabigatran among patients with DM and to describe the characteristics and outcomes of AF patients with DM.
Section snippets
Study participants
The detailed methods and results of the RE-LY have been published previously [17], [18], [19]. The main efficacy outcome was stroke or systemic embolism after a mean follow-up duration of 2 years. Patients were eligible if they had documented non-valvular AF and at least one of the following risk factor for stroke: previous ischemic stroke or transient ischemic attack (TIA); a left ventricular dysfunction; New York Heart Association class II or higher within 6 months before screening; or age ≥ 75
Results
Among 18,113 patients enrolled in the RELY trial, 4221 patients (23.3%) had DM. Patients with DM were younger with a greater body mass index (BMI), and more likely to have hypertension, coronary artery disease and peripheral vascular disease (p < 0.01) (Table 1). The mean CHADS2 and CHA2DS2VASc scores were 3.0 and 4.4 for diabetic patients and 1.9 and 3.3 for non-diabetic patients, respectively (p < 0.01) (Table 1). Among patients receiving warfarin, the median time in INR range 2.0–3.0 was 65% for
Discussion
This analysis from RE-LY [17], [18] demonstrates that among patients with AF, DM is common and is associated with an increased risk of thromboembolic events and death, independent of the choice of oral anticoagulation in all patients. Although similar relative benefits are seen with dabigatran compared to warfarin among diabetic patients, patients with diabetes had a greater absolute risk reduction of thromboembolic events. Thus, this data suggests that dabigatran is effective even in a
Conclusions
Although warfarin is considered the standard therapy for the prevention of stroke AF related stroke, its management appears to be more difficult among patients with DM. The present sub-analysis of the RE-LY suggests that among diabetic patients, the use of dabigatran provides similar relative benefits compared to the non-diabetic population; however, the absolute benefits among diabetic patients are greater.
Potential conflicts of interest
Dr Darius has received consulting fees, lecture fees, and grant support from Boehringer Ingelheim, consulting fees from Sanofi-Aventis and Bayer Schering Pharma, and lecture fees from the Medicines Company and Eli Lill. Dr Oldgren has received institutional grant support from Boehringer Ingelheim and consulting fees and lecture fees from Bayer, Boehringer Ingelheim, and BMS. Dr Wallentin has received consulting fees, lecture fees, and grant support from Boehringer Ingelheim; consulting fees
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All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.