D: Randomized, double-blind, placebo-controlled trial (1997)
P | N = 6800, HF and LVEF < 45%, NSR 302 clinical centers in US and CanadaExcluded: afib/flutter, cardiac surgery or PCI within previous 4 weeks or need for cardiac surgery or PCI in near future |
I | Digoxin |
C | Placebo |
O | Efficacy:
Safety:
|
**Retrospective Analysis: Relationship of serum digoxin concentration to mortality and morbidity in the DIG trial** (2005):
For women:
- 0.5-0.9ng/mL: Beneficial effect of digoxin on morbidity and no excess mortality
- > 1.2ng/mL (= 1.5 nmol/L): Risk for mortality was greater than placebo
**Association of serum digoxin concentration and outcomes in patients with heart failure (2003): Post-hoc analysis of the DIG trial
For men:
- 0.5-0.8ng/mL: associated with reduction in mortality
- 0.9-1.1ng/mL: not associated with reduction in mortality
- > 1.2ng/mL (= 1.5 nmol/L): higher mortality in men
Take-home messages:
- Efficacy of digoxin in heart failure:
- Reducing risk for hospitalizations for worsening HF
- Monitor digoxin trough levels (30min prior to dose)
- Levels should at least be 8-12 hours after dose
- CCS AF guidelines: maximum trough digoxin serum concentration: 1.5 nmol/L
- DIG trial suggests that > 1.5 nmol/L associated with greater mortality in HF
- CCS compendium for HF
- Digoxin trough level in HF patients with severe renal dysfunction: <1nmol/L
- If rapid deterioration in renal fx, hold digoxin and R/A when stable
- Role of digoxin: in patients who are in SR + moderate to severe symptoms, despite optimized HF therapy → relieve symptoms + reduce hospitalizations
- Concurrent atrial fibrillation:
- Digoxin – target HR of <100bpm
- Not as effective as controlling HR vs BB or CCBs during exercise
– should not be used as monotherapy for active patients - CCS guidelines for atrial fibrillation:
If used for treating patients with concomitant LV systolic dysfunction, its use should be dictated by the recommendations of the CCS HF Clinical Guidelines
1.0ng/mL = 1.3 mmol/L – associated with increased mortality in HF