#139 Digoxin: Old friend or best left on the shelf?
CLINICAL QUESTION
Does digoxin change clinical outcomes for patients with congestive heart failure or atrial fibrillation?
BOTTOM LINE
For systolic congestive heart failure (CHF), a randomized controlled trial (RCT) demonstrated that digoxin decreases CHF related hospitalizations (for one in 13 patients) without altering mortality. Stopping digoxin in stable CHF patients may worsen symptoms. Post-hoc analysis suggests low serum digoxin levels may actually decrease mortality. Cohort data for atrial fibrillation (AF) or CHF suggests digoxin increases mortality, although cause and effect is not established.
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EVIDENCE
- Systolic CHF:
- High quality RCT of 6,800 patients (NYHA class II-III, mean age 63) on digoxin (median 0.25 mg/day) or placebo1 which contributed 98% of outcomes to subsequent systematic review2 found at three years:
- Overall mortality or hospitalizations: No difference.
- CHF hospitalizations: 27% Digoxin versus 35% placebo, Number Needed to Treat (NNT)=13.
- Limitation: Study occurred before routine beta blocker (BB) use.
- Post-hoc analysis:3
- Digoxin levels:
- <0.9 ng/ml: 6% absolute lower mortality and overall hospitalizations rate compared to placebo.
- >1.2 ng/ml: 12% absolute higher mortality.
- Digoxin levels:
- 12 week RCTs of Digoxin withdrawal in stable CHF resulted in:4,5
- Clinical deterioration (necessitating study withdrawal)4 or treatment failure (adding/increasing CHF meds, emergency department visit/admission)5
- Number Needed to Harm ~5.4,5
- Deterioration more likely in patients older, not on angiotensin converting enzyme inhibitors (ACEI) or more cardiomegaly/CHF symptoms.6
- High quality RCT of 6,800 patients (NYHA class II-III, mean age 63) on digoxin (median 0.25 mg/day) or placebo1 which contributed 98% of outcomes to subsequent systematic review2 found at three years:
- AF:
- A systematic review of 12 cohort studies (235,047 patients)7 including three largest studies from US,8 Sweden,9 and Canada10 using digoxin post hospital discharge8,9 or outpatient visit9,10 demonstrated a 29% increased mortality associated with digoxin (HR 1.29; 95% CI, 1.21-1.39).
- Limitations: Unsure if possible residual confounding (patients receiving digoxin are sicker).
- A systematic review of 12 cohort studies (235,047 patients)7 including three largest studies from US,8 Sweden,9 and Canada10 using digoxin post hospital discharge8,9 or outpatient visit9,10 demonstrated a 29% increased mortality associated with digoxin (HR 1.29; 95% CI, 1.21-1.39).
- Current guidelines recommend digoxin after:
- Diuretics, ACEI, BBs, and aldosterone antagonists in CHF.11
- Calcium channel blockers or BBs in AF.12
- Clinical symptoms, age, and renal function should guide digoxin dosing, digoxin levels being ordered if questioning toxicity.
- Digoxin toxicity typically presents with cardiac arrhythmias, visual, or gastrointestinal symptoms13 and remains a relatively common reason for hospitalizations in the elderly.14
