Physicians' Academy for Cardiovascular Education

Digoxin discontinuation associated with worse outcomes in HFrEF

Digoxin Discontinuation and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction

Literature - Malik A, Masson R, Singh S, et al. - J Am Coll Cardiol 2019;74:617–27,

Introduction and methods

The ACC/AHA guideline for management of heart failure (HF) recommends that digoxin may be used, unless contraindicated, to decrease HF hospitalizations in patients with HFrEF [1]. The Digitalis Investigation Group randomized controlled trial showed that use of digoxin resulted in reduced risk of all-cause and HF hospitalizations in HFrEF patients, but did not reduce all-cause mortality [2-4]. Lack of mortality benefit combined with new guideline-directed medical therapies (GDMT) have resulted in a dramatic decline in use of digoxin [5]. Some studies have suggested that discontinuation of digoxin therapy is associated with increased risk of adverse outcomes in ambulatory patients with HFrEF [6-8]. Patients in these studies received ACE inhibitors, but not beta-blockers or MRAs.

The Medicare-linked OPTIMIZE-HF registry [9] was used to examine the relationship between discontinuation of pre-admission digoxin and outcomes in hospitalized HFrEF patients who receive more contemporary GDMT.

The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) registry was a national web-based registry of acute HF between March 1, 2003 and December 31, 2004. Before admission 3449 patients received digoxin and in 721 of these patients digoxin was discontinued before discharge. Propensity score matching was applied to patients with continuation and discontinuation of digoxin therapy, resulting in groups of 698 patients. Outcomes were HF readmission, all-cause readmission, all-cause mortality and combined endpoint of HF readmission or all-cause mortality at 30 days, 6 months, 1 year and 4 years after hospital discharge.

Main results


In a cohort of hospitalized HFrEF patients who received more contemporary GDMT including ACEi/ARBs, beta-blockers and MRAs, discontinuation of digoxin was associated with worse outcomes after 30 days, 6 months, 1 year and 4 years after hospital discharge compared to continuation of digoxin. These results suggest that it may be premature to discontinue digoxin therapy in HFrEF patients even though they take more contemporary GMDT.


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