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Disturbances of heart rhythm (arrhythmias) are common during and soon after heart attacks (myocardial infarctions), and these arrhythmias often precede and lead to early death. In the 1970s, it was found that the local anaesthetic drug lignocaine (lidocaine) suppressed arrhythmias, and it seemed obvious that giving anti-arrhythmic drugs would reduce the risk of early death after heart attack. The problem was that this obvious theory was wrong, but this was difficult to recognise from small clinical trials looking only at effects on arrhythmias, not outcomes that really matter, like deaths. Large clinical trials of anti-arrhythmic drugs done to assess their effects on mortality were not reported until the late 1980s, and these showed that the drugs actually increased mortality, probably because they can increase arrhythmias. Apart from trials that were too small assessing outcomes that were of little importance to patients, how did therapeutic fashion and publication bias contribute to the delay in discovering the lethal effects of anti-arrhythmic drugs given to people experiencing heart attacks?

Therapeutic fashion and publication bias: the case of anti-arrhythmic drugs in heart attack