Milestones of Cardiovascular Pharmacotherapy: II. Digitalis

Overview

Several plant extracts containing cardiac glycosides have been used in the treatment of dropsy (oedemas) for many centuries. When William Withering 1785 published his book „An account of the foxglove and some of its medical uses“, he was aware that digitalis is effective only in certain medical forms of dropsy but did not associate this effect with the cardiac action of the drug. However, he recognised that „the motion of the heart was affected“. Although clinical experience, experimental data and haemodynamic studies supported the use of digitalis for the treatment of heart failure, repeated controversies surrounded its efficacy and appropriated indication. At the end of the last century, the issue was not whether digoxin is effective, but whether it has a role in patients with sinus rhythm treated with ACE-inhibitors and in heart failure with preserved systolic function. In 1993, two studies that assessed the effect of digoxin withdrawal noted adverse effects after discontinuation: In the RADIANCE Study, digoxin withdrawal was associated with significant worsening of heart failure and decrease in exercise capacity and LVEF, and the PROVE Trial provided strong evidence of digoxin efficacy in patients with systolic dysfunction and sinus rhythm. In the DIG Study (1997) digoxin reduced the rate of hospitalisations but did not significantly improve the survival. The reevaluation of this study by Ahmed et al. (2006), however, demonstrated that digoxin reduces mortality and hospitalisation rate in all patients including those with preserved systolic function if used in doses of 0,125–0,250 mg reaching the SDC of 0,5–0,9 ng/ml. The authors conclude that digoxin should be prescribed before adding ACE-inhibitors, angiotensin receptor blockers, aggressive diuretic therapy and before considering cardiac resynchronisation therapy, thus rehabilitating the physiological approach to the treatment of chronic heart failure, starting the treatment by restriction of physical activity and digitalis, as practised before introduction of oral diuretics, and newly suggested by Braunwald 1980. It is a logical inexpensive approach.

Key words:
digoxin, digitalis, cardiac glycosides, digitalis controversy, chronic heart failure, William Withering.