Pharmacol Ther. 2026 Feb 26:109012. doi: 10.1016/j.pharmthera.2026.109012. Online ahead of print.
ABSTRACT
Sudden cardiac death (SCD) is responsible for approximately 15-20% of deaths worldwide. The majority of SCD cases can be attributed to lethal ventricular arrhythmias arising due to coronary heart disease (CHD), which itself accounts for approximately half of all cardiovascular disease (CVD) deaths (Wong et al., 2019). There has been a long-standing interest in the development of device-based and pharmacological antiarrhythmic interventions, often trialled in conjunction with each other in those at highest risk of SCD, with the aim to reduce the risk of SCD in CHD. However, most antiarrhythmic drug trials have revealed either ineffectiveness or drug-induced adverse effects. Moreover, a large proportion of SCD cases occur outside of the hospital setting in those considered at relatively low risk of SCD (often with no previously documented existence of CHD). This cohort is unrepresented in antiarrhythmic drug trials, since the perceived risk of drug-induced adverse effects has precluded antiarrhythmic drug evaluation in these patients. For an antiarrhythmic drug to be suitable for widespread use it must be essentially devoid of adverse effects, and no such drug has yet emerged. This review will outline the current approach to SCD prevention and how the landscape has been shaped by past antiarrhythmic drug failures, before considering how new findings might be applied to aid future antiarrhythmic drug development. We conclude with consideration of a new approach to disease-selective targeting.
PMID:41763615 | DOI:10.1016/j.pharmthera.2026.109012