SGLT inhibitors prevent AF events, cardiac hospitalization, death

Sodium‐glucose co‐transporter (SGLT) inhibitors appear to protect against the development or recurrence of atrial fibrillation (AF), as well as the reduce heart failure (HF) hospitalization or cardiovascular death in type 2 diabetes mellitus (T2DM) patients with or without AF, according to a recent meta-analysis.

Pooled data from 31 trials (188,32 participants, mean age 66 years, 38.1 percent women) yielded a moderate quality evidence showing that serious AF events decreased by 25 percent with SGLT inhibitors vs placebo or no treatment (1.1 percent vs 1.5 percent; risk ratio, 0.75, 95 percent CI, 0.66–0.86; I², 0 percent), with a similar relative reduction in total AF events. [J Am Heart Assoc 2021;doi:10.1161/JAHA.121.022222]

“[The] consistent reduction in AF events highlights the promise of SGLT inhibitors both in primary prevention for high‐risk patients and as therapy to reduce progression in those with AF. Retrospective analyses of large, population‐wide pharmacovigilance databases have also suggested that patients prescribed SGLT inhibitors have a lower rate of AF compared with patients treated with other glucose‐lowering therapies,” the investigators said. [medRxiv 2021;doi:10.1101/2021.01.04.21249211; Cardiovasc Diabetol 2021;20:1-8]

Meanwhile, the risk of HF hospitalization and cardiovascular death in T2DM patients with AF dropped by 30 percent across three trials (hazard ratio, 0.70, 95 percent CI, 0.57–0.85; I², 0 percent). This effect estimate was similar to that obtained among T2DM patients without AF.

“Because patients with and without AF benefited from a similar relative reduction in these outcomes, these findings suggest that patients with AF could benefit from a greater absolute risk reduction from SGLT inhibitors when compared with patients without AF,” the investigators explained.

However, they acknowledged that there is no conclusive evidence on whether SGLT inhibitors could improve outcomes of patients with AF who would not have been eligible for trials, in particular those without diabetes mellitus.

Of the studies included in the meta-analysis, 28 enrolled patients with diabetes mellitus, two trials enrolled patients with HF, six included patients with chronic kidney disease, and seven involved patients at high cardiovascular risk. A total of 29 trials studied an SGLT2 inhibitor (canagliflozin in six, dapagliflozin in eleven, empagliflozin in eight, and ertugliflozin in four), whereas two studied the dual SGLT1/2 inhibitor sotagliflozin.

“To our knowledge, this is the largest and most comprehensive systematic review to address the role of SGLT inhibitors in reducing the incidence and recurrence of AF with twice as many total AF events as any prior meta‐analysis,” the investigators said.

“There are multiple possible mechanisms through which SGLT inhibitors may reduce AF, such as through reduction in body weight, blood pressure, and volume,” they pointed out. [Diabetologia 2018;61:2108-2117; J Kidney Dis 2021;77:94-109]

Furthermore, mechanistic studies and animal models have described that SGLT inhibitors confer benefits for atrial fibrosis and adverse remodelling, in addition to improving cellular metabolism and bioenergetics such as ion handling and mitochondrial function, according to the investigators. “Reductions in HF could also reduce AF, and vice versa.” [Cardiovasc Diabetol 2019;18:1-4; Cardiovasc Diabetol 2017;16:1-5; Front Physiol 2020;11:912]