The Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) studies involved 7,329 patients with atrial fibrillation (AF) at moderate to high risk of stroke. They were randomly assigned to warfarin or the oral direct thrombin inhibitor ximelagatran. This analysis was planned before the studies closed but the study was not blinded or randomised for digoxin.
Mortality was higher in digoxin users (255/3911 - 6.5%) compared to non-users (141/3418 - 4.1%). The hazard ratio was 1.58 [p<0.001, 95% CI 1.29 to 1.94]. After correcting for several baseline variables including study drug, age, race, gender, BMI, smoking status, BP and co-morbidities the risk remained; hazard ratio 1.53 [p<0.001 95% CI 1.22 to 1.92].
The authors conclude that, "digitalis, like other inotropic drugs, may increase mortality" but they also stress that the results must be viewed with caution because "patients were not randomised with respect to digitalis use".
The results of this analysis support the positioning of digoxin in the current NICE Guidance for AF. Beta-blockers or rate-limiting calcium antagonists are preferred initial monotherapy. Digoxin should only be used as monotherapy in predominantly sedentary patients.
Action: Clinicians should continue to follow the existing NICE Guidance using digoxin in combination with rate limiting drugs or as monotherapy in sedentary patients.