DECISION (n=1,001, 43 Dutch sites, median 36.5-month follow-up) is the first major modern RCT of low-dose digoxin in contemporary HF(m)rEF on guideline-directed therapy. The primary composite of worsening HF events plus CV mortality was lower with digoxin (RR 0.81; 95% CI 0.61–1.07) but did not reach statistical significance (p=0.133). Worsening HF events trended lower (RR 0.76); CV mortality was unchanged. Drug was well tolerated. Pooled with DIGIT-HF and DIG (n=9,013), digitalis glycosides did significantly reduce the composite (HR 0.85; p<0.001), reopening the case for digitalis as a cheap, safe add-on in HF(m)rEF.
The benefit of low-dose digoxin in contemporary patients with heart failure with reduced or mildly reduced ejection fraction (HF(m)rEF) treated according to current guidelines is unclear.
DECISION was a double-blind, randomized, placebo-controlled outcome trial conducted at 43 Dutch sites enrolling 1001 patients with symptomatic mild-to-moderate HF(m)rEF (LVEF ≤50%). Mean age was 73 years, 28% were women, and 29% had atrial fibrillation. Patients were randomized 1:1 to low-dose digoxin (target serum concentration 0.5–0.9 ng/mL) or matching placebo on top of guideline-directed medical therapy. The primary endpoint was a composite of total worsening heart failure events (hospitalizations or urgent visits) and cardiovascular mortality. Median follow-up was 36.5 months.
The primary endpoint occurred 238 times in 131 of 500 digoxin patients versus 291 times in 152 of 501 placebo patients (rate ratio 0.81; 95% CI 0.61–1.07; p=0.133). Total worsening heart failure events were lower in the digoxin group (RR 0.76; 95% CI 0.54–1.05). Cardiovascular mortality was similar (HR 0.93; 95% CI 0.69–1.26). Low-dose digoxin was generally well tolerated and safe.
Low-dose digoxin did not significantly reduce the composite of worsening heart failure events and cardiovascular mortality in contemporary HF(m)rEF, although directional benefit on worsening heart failure events was observed.
