Digoxin is one of the oldest drugs still used in cardiovascular medicine and yet one of the most controversial. Ever since its medical use was popularised by the British physician William Withering in 1785, it has been the subject of lingering debate within the medical community. In this issue of the British Journal of Cardiology, we explore the evolution of this seemingly timeless drug from its historical origins to modern day clinical use.
In the first article, Xanniedes et al. take a look back at the major scientific advances that have led to our current understanding and medical use of digoxin. From ancient wisdom and William Withering’s careful chronicling of the therapeutic benefits and side effects of the common botanical foxglove in dropsy, which still hold true today, to the discovery of its mode of action and eventual rise to become a staple in the management of heart failure (HF) and atrial fibrillation (AF) in the pre-angiotensin-converting enzyme (ACE) inhibitor era. In parallel, the authors highlight a more macabre side to the digoxin story, including issues with toxicity, disagreements between prominent physicians in the history of medicine, and conflicting evidence of the effect of digoxin on mortality. It is an illuminating story of astute clinical observation, biological discovery and the importance of methodological rigour.
In the second article, Thompson et al. review the major indications and evidence for digoxin use in contemporary clinical practice. The epidemiology, classification, current therapeutic landscape for HF and AF, and the timeline of clinical studies of digoxin are discussed, including remaining evidence gaps. Importantly, the role of prescription bias is highlighted, which may explain the finding of excess mortality associated with digoxin use in selected non-randomised trials. The authors conclude with modern day clinical settings where treatment with digoxin still plays a role and ongoing clinical trials.
In the third article, Andrews and Thompson provide a comprehensive overview of the pharmacological properties of digoxin, including common and less well-recognised side effects. Safe prescribing of digoxin requires knowledge of the narrow therapeutic index and potential interactions with other drugs. Crucially, they outline scenarios that can lead to digoxin toxicity, how this may occur even with a digoxin level within the therapeutic range and provide advice for the successful management of digoxin toxicity.
Since digoxin is still widely used by cardiologists today, the editors hope that this issue of the BJC will provide a useful reminder of why and how digoxin has managed to keep a place within the therapeutic armamentarium of AF and HF and offer practical advice for its contemporary use. Ideally, this compendium will also stimulate further research to determine whether digoxin’s limitations can be overcome, or whether it is finally time for this centuries-old drug to be replaced.
Articles in this supplement
Digitalis – from Withering to the 21st century
The modern-day role of digoxin in heart failure and atrial fibrillation – benefits and limitations
Digoxin: monitoring, limitations of its use, and managing toxicity
Conflicts of interest
RZ has received an honorarium for working on this supplement.
Rosita Zakeri
Senior Clinical Lecturer and Honorary Consultant Cardiologist, National Institute for Health and Care Research (NIHR) Advanced Fellow
King’s College London and King’s College Hospital and Guy’s and St Thomas’ NHS Trusts, London
