Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data.
OBJECTIVE
In heart failure, digitalis increases exercise capacity and reduces morbidity, but has no effect on survival. This raises the suspicion that the inotropic benefits of digitalis may be counteracted by serious adverse effects. Patients with atrial fibrillation (AF) were studied to clarify this.


METHODS
In the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) III and V studies, 7329 patients with AF at moderate-to-high risk were randomised to preventive treatment of thromboembolism, either with warfarin or the oral direct thrombin inhibitor ximelagatran. The survival of users and non-users of digitalis was investigated.


RESULTS
At baseline, 53.4% of the study population used digitalis, and these patients had a higher mortality than non-users (255/3911 (6.5%) vs 141/3418 (4.1%), p<0.001; hazard ratio (HR) = 1.58 (95% CI 1.29 to 1.94)). Digitalis users also had more baseline risk factors. After multivariate risk factor adjustment, the increased mortality persisted (p<0.001; HR = 1.53 (95% CI 1.22 to 1.92 vs 1.23 to 1.92)).


CONCLUSIONS
The results suggest that digitalis, like other inotropic drugs, may increase mortality. This may be concealed in heart failure, but be revealed in patients with AF, who need the rate-reducing effect of digitalis, but do not benefit much from an increased inotropy. Cautious interpretation of the data is mandatory since the patients were not randomised with respect to digitalis use.
Gjesdal
K
K
Ullevål University Hospital, 0407 Oslo, Norway. knut.gjesdal@medisin.uio.no
Feyzi
J
J
Olsson
S B
SB
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D001384:Azetidines / Q000627:therapeutic use; D001596:Benzylamines / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000009:adverse effects*; D004070:Digitalis; D004071:Digitalis Glycosides / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008517:Phytotherapy / Q000009:adverse effects*; D028321:Plant Preparations / Q000009:adverse effects*; D020521:Stroke / Q000401:mortality / Q000517:prevention & control; D013923:Thromboembolism / Q000401:mortality / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D002316:Cardiotonic Agents; D004071:Digitalis Glycosides; D028321:Plant Preparations; C426686:ximelagatran; D014859:Warfarin