Dapagliflozin may reduce risk for ventricular arrhythmias, sudden death
medwireNews: Post-hoc analysis of the DAPA-HF data suggests that dapagliflozin may protect people with heart failure against serious ventricular arrhythmias, cardiac arrest, and sudden cardiovascular death.
These outcomes were not specifically monitored during the trial, instead being reported as serious adverse events (SAEs) by the site investigators. However, John McMurray (University of Glasgow, UK) and study co-authors argue that “arrhythmias reported spontaneously as SAEs are likely to be the most clinically important.”
And this view is “supported by the high subsequent mortality rate in patients with an SAE report of this type in DAPA-HF,” they write in the European Heart Journal. Indeed, these people were twice as likely to die as those without a reported arrhythmia event.
The researchers note that ventricular arrhythmias are detectable in most people who have heart failure with reduced ejection fraction (HFrEF), and that sudden cardiac death as a consequence “remains the principal cause of mortality in ambulatory patients with HFrEF, particularly those with mild symptoms.”
In all, 115 (2.4%) of the 4744 DAPA-HF participants had a ventricular arrhythmia reported, and 315 (6.6%) experienced a composite outcome event of ventricular arrhythmia, cardiac arrest, or sudden death.
The rate of the composite outcome per 100 person–years was 4.1 for participants randomly assigned to receive dapagliflozin, compared with 5.1 for those given placebo, equating to a significant 21% risk reduction for the dapagliflozin group.
The researchers stress that the study interventions were given to people already taking medications “previously shown to reduce ventricular arrhythmias and sudden death,” including beta blockers in around 95%, as well as mineralocorticoid receptor antagonists and sacubitril/valsartan.
The protective effect of dapagliflozin became clear after 9 months of treatment, leading the team to suggest that it could follow on from favorable cardiac remodeling triggered by sodium-glucose cotransporter (SGLT)2 inhibition.
In a linked editorial, Peter Light (University of Alberta, Edmonton, Canada) stresses that this post-hoc analysis “should be considered as proof of principle and hypothesis generating,” and that it remains to be seen whether the reduced risk for ventricular arrhythmias is a class effect or specific to dapagliflozin.
Nevertheless, he concludes: “These are indeed exciting times for SGLT2 [inhibitor] research.”
The publication of these findings coincided with their presentation at the virtual ESC Congress 2021.
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