Characterization of myocardial infarction as an end point in two large trials of acute coronary syndromes

Myocardial infarction (MI) is a key component of composite end points in trials that evaluate new therapies in non-ST-segment elevation acute coronary syndromes. Types of MI events in these trials have not been well characterized. A similar clinical-events classification process adjudicated all suspected MI end points in the PURSUIT and PARAGON B trials. All MI end points were classified as nonprocedural, related to percutaneous coronary intervention, or related to coronary artery bypass grafting. A total of 16,173 patients was enrolled in the 2 trials, and 1,802 MI end points occurred during a 30-day follow-up. Nearly 66% of MI end points were not related to percutaneous coronary intervention or coronary artery bypass grafting. Patients who had MI compared with those who did not had higher 30-day mortality rates (13.6% vs 2.3%, p <0.001) and 6-month mortality rates (18.4% vs 4.4%, p <0.001). Patients who had been randomized to glycoprotein IIb/IIIa inhibition showed trends toward fewer MI events regardless of type. Two-thirds of MI end points in 2 large trials of acute coronary syndrome were not related to procedure. All MI types were associated with worse short- and long-term outcomes. Characterization of the type of MI provides an opportunity for more informed interpretation of clinical trial results and improved planning for future trials.     

Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial

Context  Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non–ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. Objectives  To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non–ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. Design, Setting, and Participants  The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non–ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. Interventions  Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. Main Outcome Measures  The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. Results  The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P = .008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P = .08) and transfusions (17.0% vs 16.0%, P = .16). Conclusions  Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non–ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.      

Prognostic importance of new small Q waves following non-ST-elevation acute coronary syndromes

PURPOSE: To investigate the prognostic importance of new small Q waves following an acute coronary syndrome. METHODS: We assessed 6-month mortality in 10501 patients with non-ST-elevation acute coronary syndromes who had survived 30 days and had both admission and 30-day electrocardiograms. Patients were stratified by whether they had no new Q waves (n = 9447), new 30- to 40-ms Q waves (n = 733), or new > or =40-ms Q waves (n = 321). RESULTS: Mortality was higher in patients with 30- to 40-ms Q waves than in those with no new Q waves (3.4% [25/733] vs. 2.4% [227/9447], P = 0.005), and even higher in those with > or =40-ms Q waves (5.3% [17/321], P = 0.002). After adjustment for baseline risk predictors, mortality remained higher in patients with new 30- to 40-ms Q waves (odds ratio [OR] = 1.30; 95% confidence interval [CI]: 0.85 to 1.98; P = 0.23) and those with new > or =40-ms Q waves (OR = 1.87; 95% CI: 1.13 to 3.09; P = 0.01). CONCLUSION: Patients with new small Q waves following a non-ST-elevation acute coronary syndrome are at increased risk of adverse outcomes. These small Q waves should be considered diagnostic of myocardial infarction. Further research should investigate whether even smaller QRS changes are prognostically important.     

Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy

CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation. OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased. DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997. PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization. MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality. RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both). CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.