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Centre for Evidence-
Based Medicine

Completed Harm Worksheet for Evidence-Based General Practice

Citation

Pratt CM et al. Mortality in the Survival With ORal D-sotalol (SWORD) trial: why did patients die? Am-J-Cardiol 1998: 81:869-76.

AND

Waldo AL et al. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet 1996; 348:7-12.

Are the results of this harm study valid?

  1. Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause?
    Yes - This was a randomised placebo controlled trial.
  2. Were treatment exposures and clinical outcomes measured the same ways in both groups (e.g., was the assessment of outcomes either objective (e.g., death) or blinded to exposure)?
    Yes - the major outcome was death.
  3. Was the follow-up of study patients complete and long enough?
    The trial was stopped before recruitment had completed because of the clear harm.

Do the results satisfy some "diagnostic tests for causation"?

  1. Is it clear that the exposure preceded the onset of the outcome?
    Yes - this was a randomised trial.
  2. Is there a dose-response gradient?
    Not tested; a single dose was used in the trial.
  3. Is there positive evidence from a "dechallenge-rechallenge" study?
    As the adverse outcome is death, this is not possible.
  4. Is the association consistent from study to study?
    Only one study has been powered to look at mortality
  5. Does the association make biological sense?
    Yes - it is consistent with findings for other antiarrhythmics.

Are the valid results from this harm study important?

Adverse Outcome Totals
Present (case) Absent (control)
Exposed to the Treatment Yes (Cohort)

78

a

1471

b

a + b

No (Cohort)

48

c

1524

d

c + d

Totals

a + c

b + d

a + b + c + d

In a randomised trial or cohort study:

Relative Risk (RR) = [a/(a+b)]/[c/(c+d)]

In a case-control study:

Odds Ratio (OR) (or Relative Odds) = ad/bc

In this study:

RR = (78/1549)/(48/1572)
= 1.65 (95% CI 1.15 - 2.36), p = 0.006

Should these valid, potentially important results of a critical appraisal about a harmful treatment change the treatment of your patient?

  1. Can the study results be extrapolated to your patient?
    Probably - though the patients in SWORD had recent myocardial infarction and a reduced ejection fraction, though is no reason to believe it was the underlying disease rather than the adverse effects of the d-sotalol which caused the increased mortality.
  2. What are your patient's risks of the adverse outcome?

    To calculate the NNH (the Number of patients you Need to treat to Harm one of them) for any Odds Ratio (OR) and your Patient's Expected Event Rate for this adverse event if they were NOT exposed to this treatment (PEER):
    NNH = (PEER(OR-1)+1)/(PEER(OR-1)x(1-PEER))
  3. What are your patient's preferences, concerns and expectations from this treatment?
    He finds the extrasystoles disturbing, and would like them suppressed. However, he is also aware of the risks, and is weighing the risks and benefits.
  4. What alternative treatments are available?
    Other potential anti-arrhythmic treatment has either proved dangerous or is untested. Reframing of the extrasystoles seems the most appropriate and safe treatment.

Additional Notes

The SWORD study used d-sotalol, an isomer of sotatol. There is no evidence either way on the safety of sotalol.

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