medwireNews: The sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin may reduce the risk for atrial fibrillation or atrial flutter (AF/AFL) in patients with type 2 diabetes by a fifth, a post-hoc analysis of the DECLARE-TIMI 58 trial suggests.
Dapagliflozin 10 mg/day reduced the risk for a first AF/AFL event by a significant 19% compared with placebo during a median follow-up of 4.2 years in the 17,160 trial participants, all of whom had either multiple risk factors or established atherosclerotic cardiovascular (CV) disease.
There were 264 first AF/AFL events in patients receiving the SGLT2 inhibitor versus 325 with placebo – a rate of 7.8 versus 9.6 events per 1000 patient–years.
Stephen Wiviott (Harvard Medical School, Boston, Massachusetts, USA) and co-workers report that the benefits were seen across a broad population of patients, which “importantly” included the 1116 (6.5%) individuals with a known history of AF/AFL as well as those with no such history.
The SGLT2 inhibitor reduced events in patients with and without prior AF/AFL (hazard ratio [HR]=0.79 and 0.81, respectively), those with atherosclerotic CV disease or multiple risk factors (HR=0.83 and 0.78), and those with and without a history of heart failure (HF; HR=0.78 and 0.81).
The reduction was similar irrespective of age, gender, glycated hemoglobin level, BMI, systolic blood pressure, and estimated glomerular filtration rate, all of which have established associations with AF/AFL risk.
A total of 769 AF/AFL events occurred in 589 patients during follow-up and, among these participants, 124 had two events, 36 had three events, and 20 had four or more events.
Dapagliflozin reduced the total number of AF/AFL events, both first and recurrent, with 337 events with active treatment versus 432 with placebo (incident rate ratio=0.77). Further analysis revealed a treatment effect for a first, second, and third event (HRs=0.81, 0.69, and 0.50, respectively).
The researchers suggest in Circulation that the benefits may occur because SGLT2 inhibitors promote natriuresis and diuresis, thereby reducing atrial dilation.
“Furthermore, SGLT2 [inhibitors] have been linked to a reduction in epicardial fat, a biologically highly-active tissue that has been associated with an increase in incidence and severity of AF,” they add.
“Moreover, glycemic variations and specifically hypoglycemia have been linked to an increased risk of AF in patients with [type 2 diabetes mellitus].”
The main findings from DECLARE-TIMI 58, reported in 2018, found a significant reduction in one of the primary endpoints of CV death or HF hospitalization with dapagliflozin versus placebo but not in the co-primary endpoint of major adverse cardiovascular events.
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Circulation 2020; doi:10.1161/CIRCULATIONAHA.119.044183