Prognostic utility of quantifying evolutionary ST-segment depression on early follow-up electrocardiogram in patients with non-ST-segment elevation acute coronary syndromes.

AIMS: Although ST-segment depression (STD) on the admission electrocardiogram (ECG) confers adverse prognosis in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), the implications of STD on follow-up ECG remain uncertain. We determined the prognostic significance of STD on follow-up ECG performed within 12-24 h of admission and whether its quantitative evaluation can further refine risk stratification. METHODS AND RESULTS: The admission and follow-up ECGs of 3877 patients in the SYNERGY trial were analysed for the presence (>or=1 mm) and extent (maximum magnitude on any single lead) of STD. Of the 1110 patients presenting with STD on admission, 534 (48.1%) with persistent STD at follow-up had higher mortality at 30 days (7.1 vs. 3.6%, P = 0.01) and 6 months (10.7 vs. 5.2%, P = 0.001) than those with normalized STD. Among 2767 patients without STD on admission, 174 (6.3%) developed new STD on follow-up ECG and experienced increased mortality compared with those without such interval change (30 days: 4.0 vs. 1.7%, P = 0.035; 6 months: 8.0 vs. 3.3%, P = 0.001). After adjustment for established clinical prognosticators and the extent of STD on admission, every 1 mm increment of STD on the follow-up ECG independently predicted a graded increase in 30-day mortality [hazards ratio (HR) = 1.60, 95% confidence interval (CI) = 1.29-1.98, P < 0.0001], and death/myocardial infarction at 30 days (HR = 1.19, 95% CI = 1.03-1.36, P = 0.017) and 6 months (HR = 1.17, 95% CI = 1.03-1.32, P = 0.016). CONCLUSION: The magnitude of STD on a routine 12-24 h follow-up ECG provides incremental prognostic information beyond established clinical prognosticators and the extent of STD on admission. Incorporating a follow-up ECG and its quantitative evaluation for STD may further refine risk stratification of patients with NSTE-ACS.

Time to coronary angiography and outcomes among patients with high-risk non ST-segment elevation acute coronary syndromes: results from the SYNERGY trial.

BACKGROUND: Optimal timing for an early invasive strategy in patients with non-ST-segment-elevation acute coronary syndrome remains unclear. We evaluated the relationship between time from hospital admission to coronary angiography and outcomes in high-risk patients with non-ST-segment-elevation acute coronary syndrome who underwent angiography within 48 hours of admission. METHODS AND RESULTS: Data from 10 027 patients enrolled in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were analyzed. Patients were grouped by 6-hour intervals of time from hospital admission to coronary angiography. Primary outcomes were 30-day death or myocardial infarction, in-hospital Thrombolysis In Myocardial Infarction (TIMI) and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) major bleeding, and blood transfusion. Adjusted estimates of event rates were obtained by use of a multivariable methodology that included possible confounders through baseline and accounted for propensity of time to angiography. The landmark method was used to calculate odds ratios and 95% confidence intervals of outcomes for each time period adjusted for baseline and postbaseline clinical events. Overall, 9216 patients (92%) underwent angiography, 6352 (63%) within 48 hours. Unadjusted and adjusted rates of death/myocardial infarction increased with increasing time to angiography. The adjusted odds ratio for death/myocardial infarction in patients receiving angiography in <6 hours was 0.56 (95% confidence interval 0.41 to 0.74), whereas after 30 hours, there was no significant benefit compared with further delayed angiography. Major bleeding and transfusion did not vary significantly across time-to-angiography intervals. CONCLUSIONS: A decrease in the time to coronary angiography was associated with fewer ischemic outcomes and no increase in bleeding. Randomized clinical trials are needed to provide definitive evidence on optimal timing of coronary angiography but are difficult to design and conduct. Ongoing trials should instead clarify whether delaying angiography to administer aggressive upstream antithrombotic therapies is effective in the current setting of non-ST-segment-elevation acute coronary syndrome management.

Cigarette smoking and acute coronary syndromes: a multinational observational study.

PURPOSE: To determine the impact of cigarette smoking on the presentation, treatment, and in-hospital outcomes of patients admitted with the full spectrum of acute coronary syndromes. METHODS: GRACE is a multinational observational registry involving 94 hospitals in 14 countries. This analysis is based on 19,325 patients aged at least 18 years admitted for acute coronary syndromes as a presumptive diagnosis with at least one of the following: electrocardiographic changes consistent with acute coronary syndromes, serial increases in serum biochemical markers of cardiac necrosis, and/or documentation of coronary artery disease. The main outcomes measured were mode of presentation, treatment and in-hospital death in the ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina groups to assess the impact of smoking status. RESULTS: Smokers were more frequently diagnosed with ST-segment elevation myocardial infarction (46.0%) than former smokers (27.4%) and non-smokers (30.2%) (P<0.001). Smokers were mostly men, were younger and more aggressively treated than former smokers and non-smokers across the three acute coronary syndrome groups. Unadjusted in-hospital mortality rates were lower in smokers compared with former smokers and non-smokers in the study population (3.3%, 4.5%, and 6.9%, respectively, P<0.001), and in the ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction groups. However, by multivariate logistic analysis, the adjusted in-hospital mortality rate was similar regardless of smoking status. CONCLUSIONS: There is no survival advantage related to current or prior cigarette smoking in patients admitted with acute coronary syndromes, regardless of presentation. In this large multinational registry, the smokers' paradox does not exist.

Late Consequences of Acute Coronary Syndromes: Global Registry of Acute Coronary Events (GRACE) Follow-up.

PURPOSE: Short-term outcomes have been well characterized in acute coronary syndromes; however, longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore, we describe the longer-term outcomes, procedures, and medication use in Global Registry of Acute Coronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performance of the discharge GRACE risk score in predicting 2-year mortality. METHODS: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome were enrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronary syndrome diagnosis in 57 sites. RESULTS: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge, 14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery, and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), beta-blocker (80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heart failure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE risk score was highly predictive of all-cause mortality at 2 years (c-statistic 0.80). CONCLUSION: In this large multinational cohort of acute coronary syndrome patients, there were important later adverse consequences, including frequent morbidity and mortality. These findings were seen in the context of additional coronary procedures and despite continued use of evidence-based therapies in a high proportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors for predicting longer-term mortality was maintained.

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.

Management and outcomes of patients presenting with STEMI by use of chronic oral anticoagulation: results from the GRACE registry.

AIMS: To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy. METHODS: Using data from the Global Registry of Acute Coronary Syndromes (GRACE), patient characteristics, treatment, and reperfusion strategies of STEMI patients on chronic OAC are described, and relevant variables compared with patients not on chronic OAC. Six-month post-discharge mortality rates were evaluated by Cox proportional hazard models. RESULTS: Of 19,094 patients with STEMI, 574 (3.0%) were on chronic OAC at admission. Compared with OAC non-users, OAC users were older (mean age 73 vs. 65 years), more likely to be female (37 vs. 29%), were more likely to have a history of atrial fibrillation, prosthetic heart valve, venous thromboembolism, or stroke/transient ischaemic attack, had a higher mean GRACE risk score (166 vs. 145), were less likely to be Killip class I (68 vs. 82%), and were less likely to undergo catheterization/percutaneous coronary intervention (52 vs. 66%, respectively). Of the patients who underwent catheterization, fewer OAC users had the procedure done within 24 h of admission (56.5 vs. 64.5% of OAC non-users). In propensity-matched analyses (n=606), rates of in-hospital major bleeding and in-hospital and 6-month post-discharge mortality were similar for OAC users and OAC non-users (2.7 and 3.7%, p=0.64; 15 and 13%, p=0.56; 15 and 12%, p=0.47, respectively), rates of in-hospital recurrent myocardial infarction (8.6 and 2.0%, p<0.001) and atrial fibrillation (32 and 22%, p=0.004) were higher in OAC patients, and rates of 6-month stroke were lower (0.6 and 4.3%, p=0.038). Patients in both groups who underwent catheterization had lower mortality than those who did not undergo catheterization. CONCLUSIONS: This is the largest study to describe the characteristics and treatment of STEMI patients on chronic OAC. The findings suggest that patients on chronic OAC are less likely to receive guideline-indicated management, but have similar adjusted rates of in-hospital and 6-month mortality.

Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent?

AIMS: To identify factors associated with the use of single or dual antiplatelet therapy in patients prescribed warfarin following coronary stenting and to investigate whether single (aspirin or thienopyridine) vs. dual antiplatelet therapy plus warfarin leads to an excess of adverse outcomes. METHODS AND RESULTS: We analysed data from 800 patients with an acute coronary syndrome who underwent coronary stenting (130 patients received a drug-eluting stent) and were discharged on warfarin and either dual (n = 580) or single (n = 220) antiplatelet therapy. The use of single antiplatelet therapy was more common in Europe than in the USA (34 vs. 17%, P < 0.001). There was no difference in major bleeding in hospital or in 6-month mortality or myocardial infarction. In the single antiplatelet group, the use of either aspirin or thienopyridine (clopidogrel or ticlopidine) in combination with warfarin resulted in similar outcomes. CONCLUSION: Use of single vs. dual antiplatelet therapy and warfarin following stenting is common. In this observational study, there was no difference in mortality or myocardial infarction at 6 months; however, larger trials are needed to assert any firm recommendations.

Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial.

OBJECTIVES: We sought to evaluate whether enoxaparin (ENOX) is superior to unfractionated heparin (UFH) as adjunctive therapy for patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy and subsequently undergo percutaneous coronary intervention (PCI) by analyzing data from the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial. BACKGROUND: Limited data are available on the use of ENOX compared with UFH as adjunctive therapy in STEMI patients treated with fibrinolytic therapy and subsequent PCI. METHODS: A total of 20,479 STEMI patients who received fibrinolytic therapy were randomized to a strategy of ENOX throughout index hospitalization or UFH for at least 48 h, with blinded study drug to continue if PCI was performed. The primary end point of death or recurrent MI through 30 days was compared for ENOX versus UFH among the patients who underwent subsequent PCI (n = 4,676). RESULTS: After initial fibrinolysis, fewer patients underwent PCI through 30 days in the ENOX versus the UFH group (22.8% vs. 24.2%; p = 0.027). Among patients who underwent PCI by 30 days, the primary end point occurred in 10.7% of ENOX and 13.8% of UFH patients (0.77 relative risk; p < 0.001). There were no differences in major bleeding for ENOX versus UFH (1.4% vs. 1.6%; p = NS). Results were similar when PCI was carried out in patients receiving blinded study drug during PCI (n = 2,178). CONCLUSION: Among patients treated with fibrinolytic therapy for STEMI who underwent subsequent PCI, ENOX administration was associated with a reduced risk of death or recurrent MI without difference in the risk of major bleeding. The strategy of ENOX support for fibrinolytic therapy followed by PCI is superior to UFH and provides a seamless transition from the medical management to the interventional management phase of STEMI without the need for introducing a second anticoagulant in the cardiac catheterization laboratory.

Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal.

OBJECTIVES: Our objective was to analyze the impact of arterial access site, sheath size, timing of sheath removal, and use of access site closure devices on high-risk patients with acute coronary syndromes (ACS). BACKGROUND: In the SYNERGY trial, 9,978 patients with ACS were randomly assigned to receive enoxaparin or unfractionated heparin. METHODS: This analysis includes 9,404 patients for whom sheath access information was obtained for the first PCI procedure or diagnostic catheterization. Comparisons of baseline, angiographic, and procedural characteristics were carried out according to access site and sheath size. RESULTS: Overall, 9,404 (94%) patients underwent angiography at a median of 21 hr (25th and 75th percentiles: 5, 42) and 4,687 (50%) underwent PCI at a median of 23 hr (6,49) of enrollment. The access site was femoral for 94.9% of cases, radial for 4.4%, and brachial for 0.7%. Radial access was associated with fewer transfusions than femoral access (0.9% vs. 4.8%, P=0.007). For femoral access, the rates of noncoronary artery bypass grafting (CABG)-related TIMI major bleeding by sheath size was 1.5% for 4 or 5 French (Fr), 1.6% for 6 Fr, 3.3% for 7 Fr, and 3.8% for >or=8 Fr (P<0.0001). After adjustment for baseline characteristics, femoral access site, larger sheath size, and delayed sheath removal were independent predictors of need for transfusion. CONCLUSIONS: Smaller sheaths, radial access, and timely sheath removal may mitigate the bleeding risk associated with potent antithrombotic/platelet therapy and early catheterization.

Access to catheterisation facilities in patients admitted with acute coronary syndrome: multinational registry study.

OBJECTIVE: To investigate the relation between access to a cardiac catheterisation laboratory and clinical outcomes in patients admitted to hospital with suspected acute coronary syndrome. DESIGN: Prospective, multinational, observational registry. SETTING: Patients enrolled in 106 hospitals in 14 countries between April 1999 and March 2003. PARTICIPANTS: 28,825 patients aged > or = 18 years. MAIN OUTCOME MEASURES: Use of percutaneous coronary intervention or coronary artery bypass graft surgery, death, infarction after discharge, stroke, or major bleeding. RESULTS: Most patients (77%) across all regions (United States, Europe, Argentina and Brazil, Australia, New Zealand, and Canada) were admitted to hospitals with catheterisation facilities. As expected, the availability of a catheterisation laboratory was associated with more frequent use of percutaneous coronary intervention (41% v 3.9%, P < 0.001) and coronary artery bypass graft (7.1% v 0.7%, P < 0.001). After adjustment for baseline characteristics, medical history, and geographical region there were no significant differences in the risk of early death between patients in hospitals with or without catheterisation facilities (odds ratio 1.13, 95% confidence interval 0.98 to 1.30, for death in hospital; hazard ratio 1.05, 0.93 to 1.18, for death at 30 days). The risk of death at six months was significantly higher in patients first admitted to hospitals with catheterisation facilities (hazard ratio 1.14, 1.03 to 1.26), as was the risk of bleeding complications in hospital (odds ratio 1.94, 1.57 to 2.39) and stroke (odds ratio 1.53, 1.10 to 2.14). CONCLUSIONS: These findings support the current strategy of directing patients with suspected acute coronary syndrome to the nearest hospital with acute care facilities, irrespective of the availability of a catheterisation laboratory, and argue against early routine transfer of these patients to tertiary care hospitals with interventional facilities.

Stenting and glycoprotein IIb/IIIa inhibition in patients with acute myocardial infarction undergoing percutaneous coronary intervention: findings from the global registry of acute coronary events (GRACE).

Stenting and GP IIb/IIIa inhibition are promising adjunctive therapies in PCI. The Global Registry of Acute Coronary Events (GRACE) is a registry of unselected patients with acute coronary syndromes, allowing for the study of treatments in a real-world environment. Data from GRACE patients with AMI who underwent PCI were analyzed. After adjusting for demographics, baseline characteristics, and previous medications, treatment with GP IIb/IIIa inhibitors and a stent and treatment with a stent alone were significant predictors of survival at 6 months. Stents were used in 90.9% of patients. GP IIb/IIIa inhibitors were used in 59.7%; in most cases they were started after the beginning of the procedure. The in-hospital death rate (7.6%) was highest in patients undergoing urgent PCI. Mortality at 6 months following PCI was 14.4% among patients who received neither GP IIb/IIIa inhibitors nor a stent, compared to patients who received both GP IIb/IIIa inhibitors and a stent (7.3%), GP IIb/IIIa inhibitors alone (12.8%), or a stent alone (6.7%).