DIGOXIN USE IN CONGESTIVE-HEART-FAILURE - CURRENT STATUS

The use of digitalis in congestive heart failure with normal sinus rhy thm is still debated. While older uncontrolled, withdrawal studies fro m 1969 to 1983 provided incomplete data, with poorly documented clinic al status and poor haemodynamic and exercise data, some patients did i mprove clinically when digitalis treatment was utilised. Randomised, d ouble-blind, placebo-controlled trials from 1977 to 1991 were of bette r quality but still short in duration, with small sample sizes and sti ll with incomplete haemodynamic and exercise data. In 1993, the Prospe ctive Randomised Study of Ventricular Failure and Efficacy of Digoxin (PROVED) and Randomised Assessment of Digoxin on Inhibitors of the Ang iotensin-Converting Enzyme (RADIANCE) study, followed in 1997 by the D igitalis Investigation Group (DIG) trial, documented that digoxin prev ents clinical deterioration and hospitalisations, and improves exercis e tolerance and left ventricular function, but has no effect on surviv al. A substudy of the DIG trial showed no detrimental effect of digoxi n on survival in patients with ejection fraction CEF) of > 45%, i.e. l eft ventricular (LV) diastolic dysfunction. Therefore, digoxin appears to be the first inotrope with no detrimental effect on survival in he art failure. In addition, the neurohormonal effect of digoxin has been documented, and is possibly present with dosages even lower than 0.25 mg. Finally, it has been determined that patients with only mild heart failure do obtain documented benefit from administration of this drug . Ever since the introduction of digitalis by William Withering in 178 5,([1]) physicians have been debating its value in congestive heart fa ilure with normal sinus rhythm. Such a debate was that between two emi nent clinicians, Sir James MacKenzie and Henry Christian, co-editors o f Oxford Medicine, in 1922.([2]) Sir James advocated the use of digita lis only in heart failure with associated atrial arrhythmias. Dr Chris tian argued that its effectiveness appeared to be irrespective of whet her or not the pulse was irregular. Dr Arthur Hollman, biographer of S ir Thomas Lewis, was interviewed on American College of Cardiology ACC EL tape in June 1997 and said that Sir Thomas 'did not believe digital is was a stimulant in heart failure with normal sinus rhythm'.([3]) In this interview Dr Hollman's interpretation was that 'since the debate has continued for so long, digitalis must not be very valuable'. Pool e-Wilson and Robinson([4]) considered digoxin a redundant drug in cong estive heart failure in 1989, essentially superseded by angiotensin co nverting enzyme (ACE) inhibitors. After their review of 14 uncontrolle d and 6 controlled clinical trials, they concluded that: (a) digoxin e xerts a small, long term positive inotropic effect; (b) if no other dr ugs were available, digoxin would still be used but only in the more s evere cases, not in mild heart failure; (c) risks exceed advantages, e specially post myocardial infarction. As late as 1995, Dr Karl Weber r eflected in a review article: 'I personally do not use digoxin for hea rt failure, except when there is associated atrial fibrillation'.([5]) No one argues over the effectiveness of digitalis in slowing atrioven tricular (AV) conduction and the ventricular rate with atrial fibrilla tion, especially at rest. The purpose of this review is to discuss the current status of digitalis in heart failure with normal sinus rhythm .