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Re: Circadian fluctuations in the efficacy of streptokinase thrombolysis may be due to confounders

Goldhammer et al (1) concluded from their retrospective study of patients treated with streptokinase that efficacy was higher in the early evening hours. There are at least two important confounding variables which may explain these observations. Firstly, it has been previously found that the time of day has an impact not only on the incidence, but also on the severity of AMI (2). Hence, the apparent reduction in efficacy of streptokinase during early morning hours may be due to a greater degree of coronary artery obstruction. The authors adjusted for the location but not the size of the infarct. Secondly, the higher success rate in the early evenings compared to early mornings may be confounded by the fact senior clinicians are more likely to be present and available in the early evenings than in the early morning hours.

Finally, multiple tests were used in determining the statistical significance of the success rates at different times of the day. Appropriate adjustments should be made for multiple tests.

Reference

1) Goldhammer E, Kharash L, Abinader EG. Circadian fluctuations in the efficacy of thrombolysis with streptokinase. Postgrad Med J 1999; 75: 667-671.

2) Hansen O, Johansson BW, Gullberg B. The clinical outcome of acute myocardial infarction is related to the circadian rhythm of myocardial infarction onset. Angiology 1993; 44:7, 509-16.