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Summary: Twenty years ago, pathophysiologic studies showed that myocardial salvage in acute myocardial infarction depends on early intervention. A meta-analysis of the largest thrombolytic trials showed 1.6 lives savedlO00 treated for each hour closer to symptom onset, and that patients treated in the first hour have a much higher survival rate. The MITI trial found a seven-fold decrease in mortality in patients treated within 70 min of symptom onset. The GUSTO study showed similar results, except that during the first hour mortality was actually higher than in the second hour. In contrast, studies have found that while little survival benefit accrues from treatment after a 12 h delay, significant benefit is achieved by treatment between 6 and 12 h from symptom onset. Thus, mechanisms other than myocardial salvage are at work. A GUSTO substudy demonstrated considerable inhospital delays in attaining electrocardiographic readings, in deciding on the course of therapy, and most of all in the time to infuse the drug. Other delays in both presentation and treatment are related to patient characteristics such as age, gender, diabetes, and Killip class. The medical community cannot control delays in presentation, but it has been able to reduce in-hospital delays, with resultant benefits in morbidity as well as mortality. At the end of the day, reducing delay outweighs the choice of thrombolytic agent.

BackgroundLarger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes.MethodsOf 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days.ResultsIn COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P <0.01 for all analyses). In COMMA, the associations were similar but did not reach statistical significance. For the composite outcome of 90-day death, heart failure, shock and stroke, the associations with all CK-MB measures were statistically significant in both the COMMA and COMPLY trials.ConclusionsSophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.