Myocardial infarction: d-sotalol may have increased death.

Clinical bottom line (level 1b)

  1. Patients with left ventricular dysfunction after myocardial infarction who were given d-sotalol, were more likely to die than those given placebo (NNH = 50 at 148 days) .
Waldo et al: Lancet 1996; 348: 7-12
Expires October 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 546 centres, USA, UK, Italy

3121 patients (aged mean 60 years, 86% male) Left ventricular dysfunction (ejection fraction < or =40%) after recent (6-42 days) or remote (>42 days) myocardial infarction with overt heart failure. MI was defined as the presence of at least 2 of: characteristic chest pain, raised creatinine kinase or MB isoenzyme and typical electrocardiographic changes

Excluded if
  • unstable angina pectoris
  • class IV heart failure
  • history of life-threatening arrhythmia (sustained ventricular tachycardia/fibrillation or cardiac arrest) unrelated to MI
  • history of sick sinus syndrome or high-grade atrioventricular block untreated by a permanent pacemaker
  • history of recent (within 14 days) coronary angioplasty or coronary artery bypass surgery
  • electrolyte abnormalities (serum potassium <4.0 mmol/L or magnesium <0.75 mmol/L)
  • creatinine clearance <50 mL/minute
  • corrected QT (QTc) >460 ms
  • use of concomitant drugs (except ß -adrenergic blockers, calcium channel blockers or digoxin) or drugs that prolong QT interval
  • informed consent not given


    • Control Group: (n = 1572, 1572 analysed): placebo- matched to study drug
    Experimental Group: (n = 1549, 1549 analysed): oral d-sotalol 100 mg twice daily for 1 week. If the dose was well tolerated with a QTc <520 ms, the dose was increased to 200 mg twice daily for 1 week more. This dose was continued if the QTc remained <560 ms.

    100% followed for 2 years mean follow-up 148 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNH
    (95% CI)
    overall deaths 148 days 48
    (3.05%)    		 78
    (5.04%)    		 -65.0%
    (-135% to -16.0%)    		 -1.98%
    (-3.36% to -0.60%)    		 50
    (30 to 167)

    Comments

    1. The trial was terminated due to an interim analysis showing significantly increased mortality in the d-sotalol group.
    2. d-Sotalol is not commercially available.

    Citation

    1. Waldo AL, Camm AJ, deRuyter H, et al: Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. Lancet 1996; 348: 7-12
    Contributor: Clare Wotton and Musab Hayatli, October 1999
    Reviewer: Dwight Peretz

    Clinical Question.
    Patient recent myocardial infarction
    Intervention or Exposure d-sotalol
    Comparison placebo
    Outcome mortality