The effect of dapagliflozin on ventricular arrhythmias, cardiac arrest, or sudden death in people with heart failure: a tick in another box for sodium-glucose cotransporter 2 inhibitors

ABSTRACT

Introduction

Despite the progress made in the treatment of heart failure with reduced ejection fraction (HFrEF) in recent years, the prognosis of the disease remains poor, with ventricular arrhythmias (VA) contributing significantly to increased mortality.

Areas covered

A recently published post hoc analysis of the DAPA-HF trial evaluated the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin versus placebo on the incidence of VA, resuscitated cardiac arrest, or sudden death among people with HFrEF. During a median follow-up of 18.2 months, the composite primary outcome occurred in 140 (5.9%) people who received dapagliflozin compared to 175 (7.4%) participants in the placebo arm (hazard ratio 0.79; 95 confidence interval 0.63–0.99, P = 0.037). Animal studies suggest that SGLT2i could ameliorate the deleterious effects of myocardial injury, through various mechanisms, including reduced sympathetic activity, improved oxidative stress, tissue oxygenation, autophagy, heart energy metabolism, and promotion of cardiac remodeling.

Expert opinion

Taken together, the above findings indicate a place for SGLT2i in future trials investigating novel treatments to improve survival in patients with acute cardiovascular episodes. This is primarily applicable for acute decompensated HF; however, their use could also be evaluated in other conditions that induce VA, such as acute coronary syndromes.

KEYWORDS:

• dapagliflozin
• heart failure
• ventricular arrhythmias
• cardiac arrest
• sudden death

Declaration of interest

T Koufakis has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Pharmaserve-Lilly and Novo Nordisk, for advisory boards from Novo Nordisk, and has participated in sponsored studies by Eli Lilly and Company. G Giannakoulas declares lecture and/or advisory board honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, ELPEN, Menarini, Merck Sharp and Dohme, Mylan, Novartis, Pfizer, Sanofi and Servier. K Kotsa has received honoraria for lectures/advisory boards and research support from AstraZeneca, Boehringer Ingelheim, Pharmaserve-Lilly, Sanofi, ELPEN, Merck Sharp and Dohme, and Novo Nordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.