Atrial fibrillation or flutter: paroxysmal: oral dofetilide increases cardioversion and maintenance of sinus rhythm compared with placebo

Clinical bottom line (level 1b)

  1. Patients with paroxysmal atrial fibrillation or flutter who took oral dofetilide compared with placebo were more likely to revert to sinus rhythm (NNT = 7 at 24 hours) .
  2. Patients who took dofetilide compared with placebo were more likely to remain in sinus rhythm (NNT = 9 at 11.5 months) .
  3. There was no clear difference in severe adverse effects between the two groups.
Sing et al: Circulation 2000; 102 : 2385-2390
Expires November 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 37 acute hospitals, USA and Canada

325 patients (aged 30 to 88; mean 67, 84% male) with atrial fibrillation or flutter for 2 to 26 weeks (confirmed on ECG)

Excluded if
  • women of child-bearing potential
  • unable to tolerate withdrawal of current anti-arrhythmic medication
  • AF or flutter from reversible noncardiac diseases
  • recent myocardial infarction, unstable angina, or heart surgery; progressive heart failure
  • sick sinus syndrome or history of polymorphic VT
  • hypotension, hypertension
  • major haematological, pulmonary, hepatic or renal disease
  • concomitant use of other anti-arrhythmic agents, anticonvulsants, diuretics, tricyclics or phenothiazines
  • history of substance abuse
  • aged < 18, > 85

    Control Group: (n = 84, 84 analysed): placebo
    Experimental Group: (n = 241, 241 analysed): dofetilide 125, 250 or 500 microgram twice daily
    Patients underwent cardioversion in hospital. Patients who failed pharmacological cardioversion received DC cardioversion.
    100% followed for 11.5 months
    Outcome notes:
    • serious adverse effects : arrhythmias

    The evidence

    Outcome Time to outcome CER EER RRR
    (95% CI)    		 ARR
    (95% CI)    		 NNT
    (95% CI)
    pharmacological conversion to sinus rhythm 24 hours 1
    (1.19%)    		 36
    (14.9%)    		 1200%
    (75% to 8900%)    		 13.8%
    (8.68% to 18.8%)    		 7
    (5 to 12)
    maintenance of sinus rhythm 11.5 months 15
    (17.9%)    		 70
    (29.1%)    		 63%
    (-1% to 170%)    		 11.2%
    (1.19% to 21.2%)    		 9
    (5 to 84)
    serious adverse effects 11.5 months 2
    (2.38%)    		 7
    (2.90%)    		 -22%
    (-480% to 74%)    		 -0.52%
    (-4.41% to 3.37%)    		 -190
    (NNT = 30 to infinity;
    NNH = 23 to infinity)

    Comments

    1. Dofetilide 250 and 500 microgram was more effective than placebo at acheiving cardioversion (p=0.015, p < 0.001). Dofetilide 500 microgram was more effective than placebo at maintaining sinus rhythm (p = 0.001)

    Citation

    1. Sing S, Zoble RG, Yellen L, et al: efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation 2000; 102 : 2385-2390
    Search Terms: from ACP Journal Club
    Contributor: Chris Ball, November 2001
    Reviewer:

    Clinical Question.
    Patient paroxysmal atrial fibrillation or flutter
    Intervention or Exposure dofetilide
    Comparison placebo
    Outcome conversion and maintenance of sinus rhythm