clinicaltrials.gov Identifier: NCT01435408.

Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index and infarct size adjusting for area at risk did not differ between the groups. Treatment with exenatide resulted in increased salvage index both among patients with normoglycemia and hyperglycemia. Thus, we conclude that the association between hyperglycemia upon hospital admission and infarct size in STEMI patients is a consequence of a larger myocardial area at risk but not of a reduction in myocardial salvage. Also, cardioprotection by exenatide treatment is independent of glucose levels at hospital admission. Thus, hyperglycemia does not influence the effect of the reperfusion treatment but rather represents a surrogate marker for the severity of risk and injury to the myocardium.

Background: Guidelines recommend primary percutaneous coronary intervention (PCI) in patients with ST-segment–elevation myocardial infarction (STEMI) presenting ≥12 hours of symptom onset in the presence of ongoing ischemia. However, data supporting this recommendation are limited. We evaluated the effect of primary PCI on reperfusion success, using cardiac magnetic resonance, in STEMI patients with signs of ongoing ischemia presenting 12 to 72 hours after symptom onset compared with STEMI patients presenting <12 hours. Methods and Results: We included 865 STEMI patients who underwent cardiac magnetic resonance just after index PCI and 3 months later. Despite equal area at risk (34±12% versus 33±12%; P =0.370), patients presenting late (n=58) had larger final infarct size (13% [interquartile range, 9–24] versus 11% [interquartile range, 4–19]; P =0.037) and smaller myocardial salvage index (0.58 [interquartile range, 0.39–0.71] versus 0.65 [interquartile range, 0.49–0.84]; P =0.021) compared with patients presenting <12 hours after symptom onset (n=807). However, 65% of late-presenting patients achieved substantial myocardial salvage ≥0.50, and area under the curve for symptom onset to PCI as predictor of a myocardial salvage index ≥0.50 was poor (0.58 [95% CI, 0.53–0.63]; P <0.001). In addition, final infarct size, salvage index and left ventricular function correlated weakly with duration from symptom onset to primary PCI ( R 2 values <0.05). Conclusions: STEMI patients with signs of ongoing ischemia treated with primary PCI 12 to 72 hours after symptom onset had less myocardial salvage and developed larger infarcts. However, a large proportion achieved substantial myocardial salvage indicating a benefit from primary PCI in late-presenting patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01435408 and NCT01960933.