Application of the Thrombolysis in Myocardial Infarction risk index in non-ST-segment elevation myocardial infarction: evaluation of patients in the National Registry of Myocardial Infarction.

OBJECTIVES: The purpose of this research was to evaluate the Thrombolysis In Myocardial Infarction risk index (TRI) to characterize the risk of death among patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: The TRI, calculated from baseline age, systolic pressure, and heart rate, was established in patients with ST-segment elevation myocardial infarction (STEMI) and is predictive of mortality. Patients presenting with NSTEMI are increasing compared to STEMI and constitute a group with varied risk. METHODS: The TRI was calculated in 337,192 patients from the National Registry of Myocardial Infarction with NSTEMI. Values and outcomes were compared with 153,486 patients with STEMI classified by reperfusion status. Comparisons of baseline characteristics and clinical outcomes stratified by TRI were made. RESULTS: There was a graded relationship between the TRI and mortality in patients with NSTEMI with a >30-fold difference in mortality rates between lowest and highest deciles (p < 0.0001). The index showed good discrimination (c = 0.73). Overall mortality in the group with NSTEMI was higher (10.9%) than patients with STEMI treated with (6.6%) but lower than for STEMI patients not receiving reperfusion therapy (18.7%). The higher risk in comparison to patients with STEMI treated with reperfusion therapy was explained largely by the higher-risk profile of the population with NSTEMI. CONCLUSIONS: There is a graded relationship between TRI and mortality in patients with NSTEMI. This simple risk index provides important information about mortality in patients across the spectrum of myocardial infarction, STEMI and NSTEMI. Early identification of NSTEMI patients who are at high risk of in-hospital mortality may provide clinicians with important information for initial triage and treatment.     

Comparison of angiographic and other findings and mortality in non-ST-segment elevation versus ST-segment elevation myocardial infarction in patients undergoing early invasive intervention

We sought to compare the angiographic findings and mortality in patients with non-ST-segment elevation (NSTEMI) versus ST-segment elevation myocardial infarction (STEMI) undergoing early invasive intervention. Of 11,872 patients enrolled in the Korean Acute Myocardial Infarction Registry from November 2005 to January 2008, we studied patients with NSTEMI undergoing early invasive intervention (n = 1,486) and those with STEMI undergoing primary percutaneous coronary intervention (n = 4,392). Multivessel coronary disease, baseline Thrombolysis In Myocardial Infarction (TIMI) flow grade 3, and the left circumflex artery as a culprit lesion occurred more frequently in patients with NSTEMI than in those with STEMI. Those with NSTEMI had a significantly lower mortality rate than those with STEMI during a median follow-up of about 12 months (3.8% vs 6.7%, p <0.001). In the patients with NSTEMI, the independent predictors of mortality included postprocedural TIMI flow grade 0 to 2 (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.01 to 9.29, p = 0.047) and multivessel coronary disease (HR 3.83, 95% CI 1.36 to 10.81, p = 0.010) but not baseline TIMI flow or infarct location. However, baseline TIMI flow grade 0 to 2 (HR 1.56, 95% CI 1.03 to 2.36, p = 0.035), anterior infarction (HR 1.69, 95% CI 1.28 to 2.23, p <0.001), multivessel coronary disease (HR 1.45, 95% CI 1.10 to 1.91, p = 0.008), and postprocedural TIMI flow grade 0 to 2 (HR 2.00, 95% CI 1.42 to 2.82, p <0.001) were all independent predictors of mortality in the patients with STEMI. In conclusion, the angiographic findings in patients from NSTEMI differ from those in patients with STEMI. Postprocedural TIMI flow and multivessel coronary disease were independent predictors of mortality in patients with NSTEMI undergoing early invasive intervention.     

Association of elevated B-type natriuretic peptide levels with angiographic findings among patients with unstable angina and non-ST-segment elevation myocardial infarction

OBJECTIVES: We hypothesized that elevated B-type natriuretic peptide (BNP) levels would be associated with a greater severity of angiographic disease and a greater extent of myocardium at risk. BACKGROUND: Elevations of BNP have been associated with increased risk of adverse outcomes in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). METHODS: Of the 2,220 patients with UA/NSTEMI enrolled in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction-18 (TACTICS-TIMI-18) trial, 276 randomized to the invasive arm had both baseline BNP levels and angiographic core laboratory data. Patients were categorized according to their baseline BNP levels as < or =80 or >80 pg/ml. RESULTS: A total of 233 patients (84%) had BNP levels >80 pg/ml, and 43 (16%) had admission BNP levels >80 pg/ml. Patients with BNP >80 pg/ml had tighter culprit vessel stenosis on quantitative coronary angiography (median stenosis 76% vs. 67%, p = 0.004) and a higher (slower) corrected TIMI frame count (median CTFC 43 vs. 30, p = 0.018) in the culprit vessel. The median BNP level was higher in patients with a left anterior descending coronary artery (LAD) versus non-LAD culprit lesion location (median BNP level 40 vs. 24 pg/ml, p = 0.005), and the culprit artery was more often the LAD in patients with BNP >80 pg/ml compared with < or =80 pg/ml (44% vs. 30%, p = 0.06). CONCLUSIONS: Among patients with UA/NSTEMI, elevated BNP levels are associated with tighter culprit stenosis, higher CTFC, and LAD involvement. These findings suggest that elevated BNP may be associated with a greater severity and extent of myocardial ischemic territory during the index event and may partly explain the association between elevated BNP and adverse outcomes.     

Relation between leucocyte count, myonecrosis, myocardial perfusion, and outcomes following primary angioplasty

We examined whether leukocytosis is a negative prognostic factor in patients who underwent primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and, if so, determined whether it is associated with impaired myocardial perfusion. Previous studies have identified leukocytosis as a predictor of mortality in AMI. Whether this association holds in patients how have undergone primary PCI using contemporary pharmacotherapy and correlates with impaired myocardial perfusion is unknown. Clinical outcomes and reperfusion success, using Thrombolysis In Myocardial Infarction (TIMI) flow and myocardial blush grades, were examined according to tertiles of baseline leukocyte count in 1,268 patients who underwent primary PCI for AMI in the CADILLAC trial. Patients with higher leukocyte count were younger and more likely to be current smokers. Preprocedure TIMI grade 0 flow was more frequent in patients with higher leukocyte counts, but postprocedural TIMI grade 3 flow rates were equally high (>94%) in all 3 groups. Myocardial blush grade 2/3 was achieved at similar rates after PCI in patients with low, intermediate, and high baseline leukocyte counts (52.0% vs 51.5% vs 50.1%, p = 0.8). Higher baseline leukocyte counts were associated with greater myonecrosis (p <0.0001) and increased mortality at 1 year (2.7% vs 4.6% vs 5.4%, respectively, p = 0.047). By multivariate analysis, baseline leukocyte count (in increments of 1,000, hazard ratio 1.07, 95% confidence interval 1.02 to 1.10, p = 0.005) and peak creatine phosphokinase (hazard ratio 1.22, 95% confidence interval 1.14 to 1.29, p <0.001) were independent predictors of 1-year mortality. In conclusion, baseline leukocytosis is an independent correlate of larger infarct and increased mortality after primary PCI in AMI, an effect not explained by decreased myocardial perfusion.     

The prognostic value of serum myoglobin in patients with non-ST-segment elevation acute coronary syndromes. Results from the TIMI 11B and TACTICS-TIMI 18 studies

OBJECTIVES: The goal of this study was to define the prognostic value of serum myoglobin in patients with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: While myoglobin is useful for the early diagnosis of myocardial infarction (MI), its role in the early risk-stratification of patients with ACS has not been established. METHODS: Myoglobin, creatine kinase-MB subfraction (CK-MB) and troponin I (cTnI) were measured at randomization in 616 patients from the Thrombolysis In Myocardial Ischemia/Infarction (TIMI) 11B study and 1,841 patients from the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Therapy-Thrombolysis In Myocardial Ischemia/Infarction (TACTICS-TIMI) 18 study. The risks for death and nonfatal MI through six months of follow-up were compared between patients with and without myoglobin elevation (>110 microg/l) in each study and in a dataset combining all eligible patients from both studies (n = 2,457). RESULTS: In a multivariate model adjusting for baseline characteristics, ST changes and CK-MB and cTnI levels, an elevated baseline myoglobin was associated with increased six-month mortality in TIMI 11B (adjusted odds ratio [OR] 2.9 [95% confidence interval [CI] 1.2 to 7.1]), TACTICS-TIMI 18 (adjusted OR 3.0 [95% CI 1.5 to 5.9]) and the combined dataset (adjusted OR 3.0 [95% CI 1.8 to 5.0]). In contrast, there was no significant association between myoglobin elevation and nonfatal MI (combined dataset adjusted OR 1.55, 95% CI 0.9 to 2.6). In TACTICS-TIMI 18, patients with versus those without myoglobin elevation were more likely to have an occluded culprit artery (28% vs. 10%; p < 0.0001) and visible thrombus (49% vs. 34%; p = 0.006) and less likely to have TIMI 3 flow (53% vs. 68%; p = 0.009). CONCLUSIONS: A serum concentration of myoglobin above the MI detection threshold (>110 microg/l) is associated with an increased risk of six-month mortality, independent of baseline clinical characteristics, electrocardiographic changes and elevation in CK-MB and cTnI. These findings suggest that myoglobin may be a useful addition to cardiac biomarker panels for early risk-stratification in ACS.     

Comparative early and late outcomes after primary percutaneous coronary intervention in ST-segment elevation and non-ST-segment elevation acute myocardial infarction (from the CADILLAC trial)

We determined the outcomes of patients with acute ST-segment elevation (STE) myocardial infarction (STEMI) and non-STEMI (NSTEMI) after primary percutaneous coronary intervention (PCI). The prognosis after primary PCI in STEMI has been extensively studied and defined. Outcomes of patients who undergo primary PCI for NSTEMI are less well established. In total, 2,082 patients with ongoing chest pain for > 30 minutes consistent with acute MI were randomized to balloon angioplasty versus stenting, each with/without abciximab. Of 1,964 patients, STEMI was present in 1,725 (87.8%) and NSTEMI in 239 (12.2%). Compared with STEMI, those with NSTEMI were more likely to have delayed time-to-hospital arrival (2.4 vs 1.8 hours, p = 0.0002) and increased door-to-balloon time (3.2 vs 1.9 hours, p < 0.0001). Patients with NSTEMI were more likely to have Thrombolysis In Myocardial Infarction grade 3 flow at baseline (37.3% vs 19.4%, p < 0.0001) and higher ejection fraction (58.7% vs 55.8%, p = 0.001), but similar rates of postprocedural Thrombolysis In Myocardial Infarction grade 3 flow. At 1 year, patients with NTEMI had similar mortality (3.4% vs 4.4%, p = 0.40) but higher rates of major adverse cardiac events (24.0% vs 16.6%, p = 0.007) that was driven by more frequent ischemic target vessel revascularization (21.8% vs 11.9%, p <0.0001). In conclusion, patients with acute MI without STE who are treated with primary PCI have marked delays to treatment, similar late mortality, and increased rates of ischemic target vessel revascularization compared with patients with STEMI, despite more favorable angiographic features at presentation and similar reperfusion success. The adverse prognosis of patients with NSTEMI should be recognized and efforts made to decrease reperfusion times.     

Improved in-hospital outcomes in acute coronary syndromes (unstable angina/non-ST segment elevation myocardial infarction) despite similar TIMI risk scores

BACKGROUND: The Thrombolysis In Myocardial Infarction (TIMI) Risk Score has been shown to predict prognosis in acute coronary syndromes (ACS) comprised of unstable angina (UA) and non-ST segment elevation myocardial infarction (STEMI). We sought to evaluate the impact of newer antiplatelet and antithrombotic therapies for ACS, such as glycoprotein IIb/IIIa inhibitors (GPI) and low molecular weight heparin (LMWH), on in-hospital outcomes over time in patients (pts) with similar TIMI risk scores. METHODS: The baseline demographics and clinical outcomes of pts with ACS (UA and non-STEMI) in 1998 (Group 1998) and 2000 (Group 2000) at a single large university medical center were compared using a prospectively collected database. In-hospital major adverse cardiac events (MACE) included death, MI, or recurrent angina that resulted in urgent revascularization. Risk was estimated by utilizing the TIMI Risk Score, which uses 7 predictor variables: age > 65 years, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50%, ST segment deviation on EKG, severe angina, prior aspirin use, and elevated cardiac biomarkers. RESULTS: Comparing Group 1998 (n = 563) and Group 2000 (n = 604), there was no difference between the mean TIMI Risk Score (2.90 1.52 vs. 2.91 1.52; p = 0.97), demonstrating a similar risk profile. Nevertheless, significant improvement in in-hospital MACE (9.1% vs. 2.8%; p < 0.001) was noted. The improvement in MACE was due to differences in rates of recurrent angina, without significant differences in death and myocardial infarction. This occurred temporally in association with a significant increase in GPI (1.0% vs. 8.3%; p < 0.01) and LMWH (0.0% vs. 15.6%; p < 0.001) use within 24 hours of presentation, and the increased utilization of intracoronary stenting (46.6% vs. 64.6%; p = 0.005), findings which were confirmed with multivariate analysis. CONCLUSION: Despite similar TIMI Risk Scores, the in-hospital outcomes of pts with ACS have improved over time. This temporal change is associated with the greater use of newer antiplatelet and antithrombotic therapies and increased utilization of intracoronary stenting.     

Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction

We hypothesized that absolute and relative neutrophilia would be associated with adverse angiographic outcomes in the 394 patient Limitation of Myocardial Infarction Following Thrombolysis in Acute Myocardial Infarction (LIMIT) Acute Myocardial Infarction (AMI) trial of fibrinolysis in ST-elevation myocardial infarction. The mean neutrophil count was 7.9 x 10(9)/L, with a mean neutrophil percentage of 72%. Patients with time from symptom onset to fibrinolytic treatment more than the median (2.7 hours) had a higher neutrophil count and percentage of neutrophils than patients with shorter time to treatment. Patients with a closed infarct-related artery at 90 minutes (Thrombolysis In Myocardial Infarction [TIMI] grade 0/1 flow) had higher neutrophil counts (8.8 +/- 3.8 vs 7.6 +/- 3.0, p = 0.02) but no difference in the percentage of neutrophils than patients with an open artery. Higher neutrophil counts were also mildly correlated with longer corrected TIMI frame counts (CTFC) in the infarct-related artery (r = 0.14, p = 0.02). Patients with impaired myocardial perfusion by TIMI myocardial perfusion grade (TMPG) had a greater percentage of neutrophils (73.2 +/- 10.7% for TMPG 0/1 vs 69.9 +/- 12.6% for TMPG 2/3, p = 0.047) but no detectable difference in neutrophil counts (8.2 +/- 3.3 vs 7.7 +/- 2.9, p = 0.24). There were no significant associations between other indexes in the cell differential and angiographic or clinical outcomes. Higher neutrophil counts remained independently associated with both closed arteries and CTFC in multivariable models controlling for age, left anterior descending artery infarct location, time to treatment, and pulse and blood pressure on admission. A greater percentage of neutrophils remained independently associated with impaired microvascular perfusion in a similar multivariable model. In patients with ST-elevation myocardial infarction, absolute and relative neutrophilia were associated with impaired epicardial and microvascular perfusion.     

Association between white blood cell count, epicardial blood flow, myocardial perfusion, and clinical outcomes in the setting of acute myocardial infarction: a thrombolysis in myocardial infarction 10 substudy

BACKGROUND: Elevation of the white blood cell (WBC) count during acute myocardial infarction (AMI) is associated with adverse outcomes. We examined the relationship between the WBC count and angiographic findings to gain insight into this relationship. Results and Methods-We evaluated data from 975 patients in the Thrombolysis In Myocardial Infarction (TIMI) 10A and 10B trials. Patients with a closed artery at 60 and 90 minutes had higher a WBC count than patients with an open artery (P:=0.02). Likewise, the presence of angiographically apparent thrombus was associated with a higher WBC count (11.5+/-5.2x10(9)/L, n=290, versus 10.7+/-3. 5x10(9)/L, n=648; P=0.008). In addition, a higher WBC count was associated with poorer TIMI myocardial perfusion grades (4-way P=0.04). Mortality rates were higher in patients with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 4.9% for WBC count 5 to 10x10(9)/L, 3.8% for WBC count 10 to 15x10(9)/L, 10.4% for WBC count >15x10(9)/L; P=0.03). The development of new congestive heart failure or shock was also associated with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 5.2% for WBC count 5 to 10x10(9)/L, 6.1% for WBC count 10 to 15x10(9)/L, 17.1% for WBC count >15x10(9)/L; P<0.001), an observation that remained significant in a multivariable model that adjusted for potential confounding variables (odds ratio 1.21, P=0.002). CONCLUSIONS: Elevation in WBC count was associated with reduced epicardial blood flow and myocardial perfusion, thromboresistance (arteries open later and have a greater thrombus burden), and a higher incidence of new congestive heart failure and death. These observations provide a potential explanation for the higher mortality rate observed among AMI patients with elevated WBC counts and helps explain the growing body of literature that links inflammation and cardiovascular disease.     

Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction

OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.     

Atherosclerotic plaque with ultrasonic attenuation affects coronary reflow and infarct size in patients with acute coronary syndrome: an intravascular ultrasound study.

BACKGROUND: No reflow following percutaneous coronary intervention (PCI) is a major concern in patients with acute coronary syndrome (ACS) and it may be influenced by the preexisting plaque type. METHODS AND RESULTS: To evaluate the impact of plaque characteristics on coronary reflow following PCI in patients with ACS, a total of 110 patients (89 acute myocardial infarction, 21 unstable angina) were assessed by intravascular ultrasound. Plaque type was categorized as either atherosclerotic plaque without ultrasonic attenuation (group 1) or atherosclerotic plaque with attenuation (group 2). External elastic membrane, plaque plus media, and lumen area were measured. Coronary flow was assessed by Thrombolysis in Myocardial Infarction (TIMI) grade and TIMI frame count. Although the final TIMI frame count was similar between the 2 groups, TIMI frame count immediately after the first balloon inflation was significantly higher in group 2 (p=0.03). Despite the similar final TIMI grade and TIMI frame count, peak creatine kinase level was significantly higher (3,035+/-2,553 vs 1,950+/-1,958 IU/L, p=0.04) and fatal arrhythmia more frequently observed (16.4% vs 2.7%, p=0.04) in group 2 than in group 1. CONCLUSIONS: Atherosclerotic plaque with ultrasonic attenuation may be related to a transient deterioration in coronary flow and as a result larger infarct size and higher incidence of fatal arrhythmia following PCI in patients with ACS. These results may help in selecting lesions suitable for distal protection devices.     

Identification of patients at high risk for death and cardiac ischemic events after hospital discharge

Background Patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) remain at risk for death and cardiac ischemic events after being discharged from the hospital. Methods We examined whether the Thrombolysis In Myocardial Infarction (TIMI) risk score for UA/NSTEMI, ascertained at presentation in patients enrolled in the TIMI 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI (ESSENCE) trials, could be used to identify patients at high risk for major cardiac events after hospital discharge. Results There were a total of 1218 major cardiac events, defined as death, nonfatal myocardial infarction, or urgent revascularization, by day 43. Of these events, 336 (28%) occurred in patients after they were discharged from the hospital. Use of the TIMI risk score for UA/NSTEMI revealed a progressive, statistically significant increase in the rate of events after leaving the hospital as the patients' baseline level of risk increased (P < .001 for χ² test for trend). For patients with a risk score of 5 to 7, treatment with enoxaparin during the acute phase was associated with an odds ratio of 0.51 (95% CI 0.29-0.91) for the occurrence of death and cardiac ischemic events after hospital discharge. Conclusions More than one fourth of the major cardiac events that will occur in the first 6 weeks occur after discharge from the hospital. Stratification at presentation on the basis of the TIMI risk score for UA/NSTEMI can be used to identify patients at high risk for these events. Among patients at high-risk, acute-phase treatment with enoxaparin significantly reduces the risk of major cardiac events after leaving the hospital. (Am Heart J 2002;143:966-70.)     

Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: We sought to determine if an underlying mechanism of the association between prolonged symptom-to-treatment times and adverse outcomes may be an association of symptom-to-treatment times with impaired Thrombolysis In Myocardial Infarction myocardial perfusion grades (TMPGs). BACKGROUND: Prolonged symptom duration among ST-segment elevation myocardial infarction (STEMI) patients undergoing fibrinolytic therapy is associated with adverse outcomes. METHODS: Angiography was performed 60 min after fibrinolytic administration in 3,845 Thrombolysis In Myocardial Infarction (TIMI) trial patients. RESULTS: The median time from symptom onset to treatment was longer among patients with impaired myocardial perfusion (3.0 h for TMPG 0/1 vs. 2.7 h for TMPG 2/3; p = 0.001). In a multivariate model, impaired tissue perfusion (TMPG 0/1) remained associated with increased time to treatment (odds ratio 1.14 per hour of delay; p = 0.007) even after adjusting for Thrombolysis In Myocardial Infarction flow grade (TFG) 3, left anterior descending infarct location, and baseline clinical characteristics. Impaired myocardial perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) was associated with longer median times to treatment (3.0 h for TMPG 2/3 vs. 2.7 h for TMPG 0/1; p = 0.017), as was abnormal epicardial flow after rescue/adjunctive PCI (3.3 h for TFG 0/1/2 vs. 2.8 h for TFG 3; p = 0.005). Thirty-day mortality was associated with longer time from onset of symptoms to treatment (6.6% mortality for time to treatment >4 h vs. 3.3%; p < 0.001), even among patients undergoing rescue PCI. CONCLUSIONS: A prolonged symptom to treatment time among STEMI patients is associated with impaired myocardial perfusion independent of epicardial flow both immediately after fibrinolytic administration and after rescue/adjunctive PCI. These data provide a pathophysiologic link between prolonged symptoms due to vessel occlusion, impaired myocardial perfusion, and poor clinical outcomes.     

Prior aspirin users with acute non-ST-elevation coronary syndromes are at increased risk of cardiac events and benefit from enoxaparin

BACKGROUND: The aim of this article was to investigate whether prior aspirin use in patients with acute coronary syndromes affects clinical outcome. The Efficacy Safety Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials have shown superiority of enoxaparin over unfractionated heparin (UFH) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the treatment effect of enoxaparin in the subset of patients reporting prior aspirin use has not been determined. METHODS: The rate of death, myocardial infarction, and urgent revascularization at days 8 and 43 after randomization was compared among patients who received aspirin within the week before randomization with those who did not receive aspirin in the TIMI 11B trial. A total of 3275 patients (84%) were prior aspirin users. RESULTS: The admission diagnosis was similar for prior and nonprior aspirin users. At both day 8 and day 43 the event rate was higher for prior aspirin users than for nonprior aspirin users (odds ratio 1.6 [1.24-2.08], P =.0004 at day 43), even after correction for baseline characteristics. Compared with those prior aspirin users taking UFH, enoxaparin-treated prior aspirin users had a reduced rate of the composite end point of death, myocardial infarction, and urgent revascularization at day 8 (odds ratio 0.82 [0.67-1.00], P =.046) and day 43 (odds ratio 0.83 [0.70-0.98], P =.032). CONCLUSION: Patients with UA/NSTEMI and prior aspirin use had a 60% higher risk of death and cardiac ischemic events compared with nonprior aspirin users. On the basis of this subanalysis, enoxaparin is superior to UFH in all patients. In prior aspirin users the benefit is more clearly demonstrated.     

介入治疗联合应用腺苷对不稳定型心绞痛患者冠状动脉血流和临床预后的影响

目的评价经皮冠状动脉介入治疗(PCI)联合静脉应用腺苷对不稳定型心绞痛(UA)患者冠状动脉血流和近期临床预后的影响。方法 2009年3～12月,60例准备行PCI的UA患者按随机数字表法分配到腺苷组(PCI术前10 min应用腺苷,30例)和对照组(PCI术前10 min应用生理盐水,30例)。观察两组在常规使用阿司匹林和氯吡格雷的基础上,PCI术前和术后即刻靶血管TIMI血流分级和校正的TIMI帧数(CTFC)。随访PCI术后3个月内两组患者主要不良心血管事件(MACE)的发生率。记录使用腺苷治疗期间不良反应的发生情况。结果两组PCI术前即刻靶血管TIMI血流2～3级发生率和CTFC差异无统计学意义(76.2%比72.5%,41.60±13.76比42.13±14.30,均为P>0.05)。两组PCI术后即刻靶血管TIMI血流3级发生率差异无统计学意义(97.6%比92.9%,P>0.05);腺苷组靶血管CTFC则显著优于对照组(23.03±8.38比28.50±10.24,P<0.05)。结论在阿司匹林、氯吡格雷抗血小板治疗的基础上,PCI联合静脉应用腺苷能改善UA患者术后靶血管冠状动脉血流。     

Intracoronary bolus administration of eptifibatide during percutaneous coronary stenting for non ST elevation myocardial infarction and unstable angina

Background: Distal embolization of thrombotic debris may occur during and after percutaneous coronary intervention (PCI) for acute coronary syndromes. This may lead to impaired microvascular perfusion, myocardial infarction and increased morbidity and mortality. In vitro studies suggest that high local concentrations of a glycoprotein IIb/IIIa inhibitor may be effective in disaggregating thrombus and thereby prevent microvascular compromise. We hypothesized that intracoronary (IC) administration of eptifibatide during stent implantation for unstable angina/non ST elevation myocardial infarction (UA/NSTEMI) would be safe and would lead to an acceptable rate of normal myocardial perfusion. Methods: In 54 patients with UA/NSTEMI, 2 boluses of 180 mcg/kg of eptifibatide each were administered via the IC route during PCI. Data were retrospectively collected and reviewed by an independent core laboratory. Results: No adverse events including arrhythmias occurred during IC administration of eptifibatide. There were no deaths or urgent revascularizations among patients treated with IC eptifibatide. One patient (2.0%) sustained a post-procedure myocardial infarction. One patient sustained a TIMI major bleeding event due to a gastrointestinal bleed. There were no TIMI minor bleeding events. Normal post PCI TIMI Myocardial Perfusion Grade was observed in 54% of patients. Conclusion: IC bolus administration of eptifibatide was feasible and safe among patients with UA/NSTEMI. Larger prospective and randomized studies are warranted to further explore the efficacy of this strategy. Abbreviated Abstract Intracoronary eptifibatide administration during PCI for UA/NSTEMI is feasible and safe.     

Clinical and angiographic correlates and outcomes of suboptimal coronary flow inpatients with acute myocardial infarction undergoing primary percutaneous coronary intervention

OBJECTIVES: The purpose of this study was to determine the clinical and angiographic correlates and outcomes of patients with suboptimal coronary flow after primary percutaneous coronary interventions (PCI). BACKGROUND: The clinical and angiographic correlates and outcomes of Thrombolysis in Myocardial Infarction (TIMI) < or =2 flow in patients treated with primary PCI are not known. METHODS: We evaluated 3,362 patients with ST elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction trials, who underwent primary PCI. RESULTS: Post-procedural final TIMI < or =2 flow occurred in 232 (6.9%) patients. Multivariate analysis identified age > or =70 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), diabetes (OR 1.9; 95% CI, 1.3 to 2.7), symptom onset to emergency room presentation (OR 1.1; 95% CI, 1.1 to 1.2); initial TIMI < or =1 flow (OR 3.2; 95% CI, 1.9 to 5.5), and left ventricular ejection fraction <50% (OR 1.7; 95% CI, 1.2 to 2.4) as independent correlates of final TIMI < or =2 flow. In-hospital (composite of reinfarction, ischemic target vessel revascularization, or death, as well as these events individually) and one-year (reinfarction and/or death) events occurred more frequently in patients with TIMI < or =2 flow. The Cox proportional hazards model identified TIMI < or =2 flow to be independently associated with one-year mortality (hazard ratio 3.8, 95% CI, 2.5 to 5.7). CONCLUSIONS: Final TIMI < or =2 flow, although uncommon after primary PCI, was strongly associated with hospital and one-year adverse events. The clustering of final TIMI < or =2 flow in high-risk groups may partially explain the poor prognosis of these patients. Awareness of these risk factors may be useful to clinicians to triage and treat patients undergoing primary PCI.     

Inflammation markers and risk stratification in patients with acute coronary syndromes: design of the SIESTA Study (Systemic Inflammation Evaluation in Patients with non-ST segment elevation Acute coronary syndromes)

BACKGROUND AND OBJECTIVE: Evidence is growing regarding the prognostic value of markers of inflammation in unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). However, the independent value of these variables has not been systematically investigated in prospective studies. The main objective of the SIESTA study is to assess the relative prognostic roles of C-reactive protein, fibrinogen, neopterin, interleukins 6, 8, 10 and 18, tumor necrosis factor, e-selectin, endothelin 1, tissue factor, VCAM-1, ICAM-1, pregnancy-associated plasma protein-A, B-type natriuretic peptide, leukocytes, troponin I or T and serum creatine kinase-MB (CKMB) in UA/NSTEMI patients. PATIENTS AND METHOD: SIESTA is a prospective, multicenter trial involving patients with chest pain suggestive of acute coronary syndrome (ACS) within 48 hours of enrolment and at least one of the following: abnormal troponin levels, electrocardiographic signs of ischaemia or previously documented vascular disease. Clinical outcome data and serial biochemical determinations will be assessed during hospital admission and at 30, 180 and 365 days of follow-up. The TIMI (Thrombolysis In Myocardial Infarction) and PEPA (Proyecto de Estudio del Pronóstico de la Angina) risk scores will be also validated. Study variables will include death due to any cause, cardiac death, non-fatal myocardial infarction, unstable angina requiring re-admission, emergency revascularization and a composite of death, myocardial infarction and need for emergency hospitalization or myocardial revascularization. Each of these conditions will be treated as secondary end-points when assessed individually.This study will provide valuable prospective information about the prognostic value of inflammatory markers in real life ACS patients of Mediterranean origin.     

Early prognostic usefulness of C-reactive protein added to the Thrombolysis In Myocardial Infarction risk score in acute coronary syndromes

The aim of the present study was to evaluate whether an elevated plasma C-reactive protein (CRP) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with acute coronary syndromes. For this purpose, 1,846 consecutive patients with either acute ST-segment elevation myocardial infarction (STEMI; 861 patients) or non-ST-segment elevation acute coronary syndrome (NSTEACS; 985 patients) were included. The incidence of 30-day death and 14-day composite of death, myocardial infarction (or repeat myocardial infarction) and recurrent ischemia was the prespecified primary end point in the STEMI and NSTEACS cohorts, respectively. The incidence of the primary end point was 9.8% and 23.6% in the STEMI and NSTEACS cohorts, respectively. A significantly increased risk of the primary end point was present with an increase in the STEMI and NSTEACS TIMI risk score (p(trend) < 0.001 for the 2 groups). A plasma CRP value of > or = 5 and > or = 3 mg/L (defined by receiver-operating characteristic analysis) was associated with a significantly increased risk of the primary end point in the STEMI and NSTEACS cohorts, respectively (p < 0.001 for the 2 cohorts), and it was true throughout the subgroups of STEMI and NSTEACS TIMI risk scores. In conclusion, an elevated plasma CRP level appears to be a marker that adds prognostic information to the validated STEMI and NSTEACS TIMI risk score. The plasma CRP and TIMI risk score may be used together for enhanced risk stratification in the setting of acute coronary syndromes.     

Effect of intracoronary thrombectomy on 30-day mortality in patients with acute myocardial infarction

Insertion of intracoronary thrombectomy (ICT) devices, as a precedent to percutaneous coronary intervention (PCI), theoretically could have a beneficial effect on the outcome in patients with acute myocardial infarction. To examine whether ICT was associated with a lower 30-day mortality rate in patients with acute myocardial infarction, we studied 3,913 patients who underwent PCI within 24 hours after onset. A total of 990 patients (25.3%) were treated with ICT before PCI. The 30-day mortality rate was lower in the patients receiving ICT than in those without (3.7% vs 6.2%, p = 0.004), but this beneficial effect disappeared after adjustment for baseline characteristics (hazard ratio [HR] 0.658, p = 0.166). We also divided the patients into tertiles according to the Thrombolysis In Myocardial Infarction (TIMI) risk score. After adjustment for baseline characteristics, ICT was associated with a lower 30-day mortality rate in patients from the highest TIMI risk score tertile (HR 0.407, p = 0.029), but not in patients from the lower 2 tertiles. ICT was also an independent predictor of a lower 30-day mortality risk in patients aged > or =70 years (HR 0.239, p = 0.007), patients with diabetes mellitus (HR 0.275, p = 0.039), and those with stent implantation (HR 0.437, p = 0.034). In conclusion, in selected patients with high TIMI risk scores, an age > or =70 years, diabetes mellitus, or stenting, ICT is associated with a lower 30-day mortality rate.