28 Should we be using digoxin in 2018?

Digoxin is often used in the management of patients with heart failure (HF) with or without atrial fibrillation (AF). There is sound biological rationale for the use of digoxin, but the data on clinical outcomes with digoxin use in this patient population are conflicting. There is a single adequately powered randomised trial of digoxin in patients with HF in sinus rhythm.1 This trial showed a small but significant reduction in the rate of hospitalisation due to HF with the use of digoxin, when compared to placebo, among patients treated with ACE inhibitors and diuretics. There was no effect on mortality.1 On the contrary, there are numerous secondary analyses of observational data from randomised trials which suggest that there may be an increased risk of death from using digoxin, both in patients with HF, those in AF, or both.2 However, observational data on digoxin use suffer from treatment bias (confounding by indication), as the sickest patients are the ones who are prescribed digoxin. Propensity matched analyses have been attempted to overcome the effect of this bias with conflicting results.2 3 However, it is likely that because the magnitude of this bias is large, no amount of statistical adjustment can yield reliable effect estimates. This highlights the need for large, randomised trials of digoxin.3 References Digitalis Investigation G. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525–533. Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GY, Steeds RP, Townend J, Kotecha D. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ 2015;351:h4451. Karthikeyan G, Devasenapathy N, Zühlke L, Engel ME, Rangarajan S, Teo KK, Mayosi BM, Yusuf S; Global Rheumatic Heart Disease Registry (REMEDY) Investigators. Digoxin and clinical outcomes in the Global Rheumatic Heart Disease Registry. Heart 2018 Sep 12. pii: heartjnl-2018-313614.