Key takeaways:

• Patients with heart failure who received an SGLT2 inhibitor were less likely to experience sudden cardiac death vs. placebo.
• There was no reduction in arrhythmic events observed with SGLT2 inhibitor use.

SGLT2 inhibitor therapy in patients with heart failure is associated with a significantly lower incidence of sudden cardiac death vs. placebo, with the benefit persisting independent of other guideline-directed medical therapies.

“The decreased incidence of sudden cardiac death in patients with HF receiving SGLT2 inhibitor therapy is directly concordant with studies demonstrating that SGLT2 inhibitor therapy has a profound impact on CV death and heart failure hospitalizations in patients with heart failure regardless of ejection fraction,” Connor Oates, MD, a cardiovascular disease fellow with MedStar Heart and Vascular Institute and Georgetown University-Washington Hospital Center, and colleagues wrote in Clinical Cardiology. “Patients with heart failure, whether characterized as HF with reduced ejection fraction or HF with preserved EF, develop fibrosis, myocardial hypertrophy, electrical and metabolic dysregulation that can predispose to atrial and ventricular tachyarrhythmias, bradyarrhythmias and other electromechanical disorders. These different mechanisms can independently lead to sudden cardiac death in patients with HF and can be directly impacted by SGLT2 inhibitor therapy.”

Oates and colleagues analyzed data from seven trials published before Aug. 28, 2022, that included participants with HF that compared the use of an SGLT2 inhibitor (n = 10,796) vs. placebo (n = 10,796) and reported on outcomes including sudden cardiac death, ventricular arrhythmias and atrial arrhythmias.

SGLT2 inhibitor therapy was associated with a significant reduction in risk for sudden cardiac death (RR = 0.68; 95% CI, 0.48-0.95; P = .03; I² = 0%). Absent dedicated rhythm monitoring, there were no significant differences in the incidence of sustained ventricular arrhythmias not associated with sudden cardiac death (RR = 1.03; 95% CI, 0.83-1.29; P = .77; I² = 0%) or atrial arrhythmias (RR = 0.91; 95% CI, 0.77-1.09; P = .31; I² = 29%) between patients who received an SGLT2 inhibitor or placebo.

“Our analysis did not demonstrate a reduction in the incidence of arrhythmic events in patients receiving SGLT2 inhibitor therapy,” the researchers wrote. “This finding, although consistent with a post-hoc analysis of DAPA-HF, is limited by the design of trials included, specifically a lack of dedicated rhythm monitoring.”

The researchers wrote that it is essential for future randomized trials of HF therapies to include dedicated rhythm monitoring to improve the characterization of sudden death.