Is the Timing of Treatment Critical?

Abstract

The timing of treatment for any condition is dependent on the underlying pathophysiology. One of the issues to consider is whether decreasing the time to intervention can be translated into recognisable benefits. Key data have been generated over the last 10 years which are relevant to the treatment of acute myocardial infarction (MI), including results of the large-scale ‘mega-trials’ in broad population groups. The therapeutic interventions which will be considered here are beta blockers, aspirin, thrombolytics and angiotensin-converting enzyme (ACE) inhibitors. Of these, aspirin seems to be the least time-dependent, provided it is administered within 12-24 h of symptom onset. Mortality benefits associated with beta Mocker therapy increase as the time of administration from symptom onset is reduced and the extent to which thrombolytic therapy is beneficial is also clearly time dependent. The results from GISSI-3 and ISIS-4, which recruited a broader patient population than in previous trials, were concordant, showing a significant improvement in survival after five to six weeks’ treatment. The message from GISSI-3 was that administration of ACE inhibitors within 24 h of symptom onset will improve survival and left ventricular function provided patients are hemodynamically stable, are not hypotensive and have no renal dysfunction; 76 lives were saved (representing an 11% risk reduction in mortality) after six weeks’ lisinopril treatment, 54 of which were saved in the first five days. However, the fact that data from the large-scale acute MI trials have not been applied to routine patient care in a consistent way must be due to reasons other than ignorance. Time-dependent efficacy is not an independent variable and other variables are of equal or greater importance.