Unstable Angina And non-ST-segment Elevation Myocardial Infarction Research Articles

Evaluation of the Relative Efficacy and Safety of Prasugrel and Clopidogrel in Medically Managed High Risk UA/NSTEMI ACS Population

Background: The term acute coronary syndrome encompasses unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Antiplatelet therapy is one of the cornerstones of therapy in UA/NSTEMI. Objective: To compare efficacy and safety of Prasugrel and clopidogrel both theinopyridines antiplatelet drugs in high risk (TIMI Score 3 or more) medically managed UA/NSTEMI. Materials and Methods: A prospective, randomized study was conducted in GNDH, Amritsar. 100 patients were included, 50 patients received Prasugrel and 50 received clopidogrel. Outcomes like angina episodes, bleeding, stroke, ischemic ECG changes, and arrhythmia were compared during hospital stay and follow-up for 3 months. Results: Prasugrel was associated with significant lower incidence of major adverse cardiac event (MACE) 9 compared to 19 with clopidogrel during hospital stay. During follow up for 3 months 2 events occurred with Prasugrel and 3 with clopidogrel which were non-significant. Conclusion: Use of Prasugrel was associated with less number of MACE than the patients who were on clopidogrel. Although for the individual adverse coronary events, except for angina there was no statically significant difference, but when the total MACE observed during the study was compared, it was significantly less in the patient on Prasugrel therapy. Safety of the Prasugrel in present study was identical to clopidogrel.

Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction

ObjectiveHigh-mobility group box 1 (HMGB1) is a damage-associated molecular pattern molecule, which suggests a potential role of this protein in the pathophysiology of acute coronary syndrome (ACS). Circulating HMGB1 has been shown to be independently associated with cardiac mortality in ST-segment elevation myocardial infarction. However, its prognostic value remains unclear in unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). MethodsHMGB1, high-sensitivity C-reactive protein (hsCRP), cardiac troponin I and B-type natriuretic peptide concentrations were measured on admission in 258 consecutive patients (mean age of 67 years) hospitalized for UA/NSTEMI within 24h (mean, 7.4h) of the onset of chest symptoms. ResultsA total of 38 (14.7%) cardiovascular deaths, including 10 in-hospital deaths, occurred during a median follow-up period of 49 months after admission. In a stepwise Cox regression analysis including 19 well-known clinical predictors of ACS, HMGB1 [relative risk (RR) 3.24 per 10-fold increment; P=0.0003], cardiac troponin I (RR 1.83 per 10-fold increment, P=0.0007), Killip class>1 (RR 4.67, P=0.0001) and age (RR 1.05 per 1-year increment, P=0.03), but not hsCRP, were independently associated with cardiovascular mortality. In-hospital and cardiovascular mortality rates were higher in patients with increased HMGB1 (≥2.4ng/mL of median value) than those without increased HMGB1 (6.3% vs. 1.5%, P=0.04; and 23% vs. 6.9%, P=0.0003). ConclusionCirculating concentration of HMGB1 on admission may be a potential and independent predictor of cardiovascular mortality in patients hospitalized for UA/NSTEMI within 24h of onset.

Pentraxin 3 in unstable angina and non-ST-segment elevation myocardial infarction

PurposeWe prospectively investigated the prognostic value of pentraxin 3 (PTX3) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). BackgroundPTX3 may be a useful marker for localized vascular inflammation and damage to the cardiovascular system. Recent studies have shown that plasma PTX3 is elevated in patients with UA/NSTEMI; however, its prognostic value in UA/NSTEMI remains unclear. MethodsPTX3, high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin I were measured on admission in 204 consecutive patients (mean age of 69 years; 144 males) hospitalized for UA/NSTEMI within 24h (mean of 7.5h) after the onset of chest symptoms. A cardiac event, which was defined as cardiac death, rehospitalization for acute coronary syndrome (ACS), or rehospitalization for worsening heart failure, was monitored for 6 months after admission. ResultsA total of 26 (13%) cardiac events occurred during the 6-month follow-up period. In a stepwise Cox regression analysis including 18 well-known clinical and biochemical predictors of ACS outcome, both PTX3 (relative risk 3.86 per 10-fold increment, P=0.01) and NT-proBNP (relative risk 2.16 per 10-fold increment, P=0.02), but not hsCRP, were independently associated with the 6-month cardiac event. The cardiac event rate was higher in patients with increased PTX3 (≥3.1ng/mL of median value) than those without (20% vs. 5.8%, P=0.003). A Kaplan–Meier analysis revealed that patients with increased PTX3 had a higher risk for cardiac events than those without (P=0.002). ConclusionPTX3 and NT-proBNP may be potent and independent predictors for 6-month cardiac events in patients hospitalized for UA/NSTEMI within 24h after the onset. Measurement of plasma PTX3 may substantially improve the early risk stratification of patients with UA/NSTEMI.

Glycoprotein IIb-IIIa Inhibitors in the Emergency Department for Patients with Non-ST-Elevation Acute Coronary Syndromes: Principles and Practices

Non-ST-elevation acute coronary syndrome is associated with significant morbidity and mortality. Although the benefit of platelet inhibition by glycoprotein (GP) IIb-IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI) is well established, emergency physicians and cardiologists have different perspectives regarding their optimum administration, especially upstream before PCI. In this article, two emergency physicians and two cardiologists analyze data and discuss relevant issues, including the ischemic benefits vs. the risk of bleeding associated with GP IIb-IIIa inhibitors in appropriate patients, for example, those with an elevated troponin level or who undergo revascularization. The emergency physicians support early identification of high-risk non-ST-elevation acute coronary syndrome patients and early administration of GP IIb-IIIa inhibitors, which are linked to improved patient outcomes. The cardiologists emphasize risk stratification to identify patients in whom the expected reduction in ischemic complications outweighs the risk of increased bleeding with these agents. GP IIb-IIIa inhibitors should be considered in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI) in whom PCI is planned, especially those with high-risk features or elevated serum troponin levels. It is reasonable to start this treatment upstream of intervention, pending further studies investigating the optimal timing of initiation of therapy in appropriate patients.

Tolerability and feasibility of eptifibatide in acute coronary syndrome in patients at high risk for cardiovascular disease: A retrospective analysis

Background: Despite the beneficial effects of glycoprotein (GP) IIb/IIIa antagonists in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), GP IIb/IIIa antagonists are rarely administered in general internal medicine wards in Israel, where most patients with UA/ NSTEMI are admitted, due to lack of adequate monitoring and safety concerns. Objective: The aims of this study were to compare the prevalence of bleeding complications in patients with UA/NSTEMI receiving combination treatment with eptifibatide (a GP IIb/IIIa antagonist), the low-molecular-weight heparin enoxaparin, and acetylsalicylic acid (ASA) versus that in patients receiving enoxaparin and ASA in internal medicine wards in Israel, and to identify risk factors for bleeding complications. Methods: This retrospective analysis included information from the database at Rambam Medical Center, Haifa, Israel. The database provided information from 4 of the 5 wards (the ward from which data were unavailable did not routinely use eptifibatide). Data were included from patients aged ≥l.8 years who were admitted to the center with a diagnosis of UA/NSTEMI, were at high risk for death and/or nonfatal ischemic events based on American College of Cardiology/American Heart Association guidelines, were to undergo coronary intervention, and who had a Thrombosis in Myocardial Infarction risk score ≥3 (moderate to high risk). Patients in the eptifibatide group received eptifibatide IV (180-μg/kg bolus followed by a continuous infusion of 2 μg/kg · min up to 72 hours), enoxaparin SC (2 mg/kg · d), and ASA (100 mg/d). Patients in the control group received enoxaparin SC (2 mg/kg - d up to 96 hours) and ASA (100 mg/d). The prevalence of bleeding events was assessed using data up to 24 hours after the end of study drug administration. Major bleeding was defined as life-threatening bleeding at any site, intracranial hemorrhage, or bleeding accompanied by a decrease in plasma hemoglobin concentration of 5 g/dL or more. Otherwise, bleeding was considered minor. The risk for bleeding events was assessed using multivariate regression analysis. Results: Data from 105 patients (64 men, 41 women) were included in the analysis. In the eptifibatide and control groups, the mean (SD) ages were 68.7 (11.1) and 74.8 (11.0) years, respectively. These characteristics were statistically similar between the 2 groups. The rates of major bleeding were similar between the eptifibatide and control groups (2 [3.8%] vs 0 patients). The rate of minor bleeding was significantly higher in the eptifibatide group compared with that in controls (11 [21.2%] vs 4 [7.5%] patients; P = 0.03). The incidence of thrombocytopenia was statistically similar between the eptifibatide and control groups (0 vs 2 [3.8%] patients). The risk for bleeding was found to be associated with eptifibatide use (odds ratio, 4.8; 95% CI, 1.29–17.80), whereas an association with treatment was not found in the control group. Conclusion: The results of this retrospective analysis suggest that the risk for bleeding complications is higher with combination treatment with eptifibatide, enoxaparin, and ASA compared with that with enoxaparin and ASA in high-risk patients with UA/NSTEMI admitted to internal medicine wards in Israel.

Practical Implementation of the Guidelines for Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction in the Emergency Department

In the United States each year, >5.3 million patients present to emergency departments with chest discomfort and related symptoms. Ultimately, >1.4 million individuals are hospitalized for unstable angina and non-ST-segment elevation myocardial infarction. For emergency physicians and cardiologists alike, these patients represent an enormous challenge to accurately diagnose and appropriately treat. This update of the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) provides an evidence-based approach to the diagnosis and treatment of these patients in the emergency department, in-hospital, and after hospital discharge. Despite publication of the guidelines several years ago, many patients with UA/NSTEMI still do not receive guidelines-indicated therapy.

Practical Implementation of the Guidelines for Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction in the Emergency Department

In the United States each year, >5.3 million patients present to emergency departments with chest discomfort and related symptoms. Ultimately, >1.4 million individuals are hospitalized for unstable angina and non–ST-segment elevation myocardial infarction. For emergency physicians and cardiologists alike, these patients represent an enormous challenge to accurately diagnose and appropriately treat. This update of the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) provides an evidence-based approach to the diagnosis and treatment of these patients in the emergency department, in-hospital, and after hospital discharge. Despite publication of the guidelines several years ago, many patients with UA/NSTEMI still do not receive guidelines-indicated therapy.

Association of Elevated B-Type Natriuretic Peptide Levels With Angiographic Findings Among Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction

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. 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). 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. 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). 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.

Association between plasmin activation system and intravascular ultrasound signs of plaque instability in patients with unstable angina and non-st–segment elevation myocardial infarction

BackgroundThe association between intravascular ultrasound (IVUS) signs of plaque instability and plasma levels of biomarkers was determined in patients with unstable angina and non-ST–segment elevation myocardial infarction (UA/NSTEMI). MethodsFifty-two patients underwent coronary angiography and IVUS 8 ± 5 hours after the onset of chest pain. IVUS analysis included plaque morphology, disruption, thrombi and eccentricity, lumen, external elastic membrane, and plaque plus media areas of culprit lesion and reference segments and arterial remodeling. Plasma levels of the thrombin activation system (thrombin-antithrombin complex [TAT], tissue factor pathway inhibitor [TFPI], and prothrombin fragments 1+2 [F1+2]) and plasmin activation system (tissue and urokinase-type plasminogen activator [t-PA and u-PA], plasminogen activator inhibitor-1 [PAI-1], and D-dimer) were measured with enzyme-linked immunosorbent assay kits before angiography. ResultsElevated levels of TAT (7.2 ± 6.0 μg/L), F1+2 (1.8 ± 1.0 nmol/L), TFPI (179.1 ± 131.0 ng/mL), PAI-1 (95.4 ± 54.6 ng/mL), t-PA (10.6 ± 8.8 ng/mL), and u-PA (2.6 ± 0.9 ng/mL) were found in patients with UA/NSTEMI. The serum levels of D-dimer (40.0 ± 39.5 ng/mL) remained in reference range. Expansive and constrictive remodeling were found in 18 (35%) and 12 (23%) patients, respectively. Expansive remodeling of the culprit lesion was associated with significantly higher plasma levels of PAI-1 (121.6 ± 55.0 vs 87.7 ± 61.5 and 77.4 ± 42.8 ng/ml, P = .039), and u-PA (3.0 ± 1.2 vs 2.2 ± 0.5 and 2.5 ± 0.7 ng/mL, P = .026) as compared with constrictive and neutral remodeling. Increased plasma levels of u-PA were associated with plaque rupture (3.0 ± 0.7 vs 2.5 ± 0.9 ng/mL, P = .062). Plasma levels of PAI-1 and u-PA correlated positively with plaque plus media (P = .0297 and P = .0093) and external elastic membrane areas (P = .010 and P = .0002). ConclusionsElevated levels of biomarkers of plasmin activation system are associated with signs of plaque instability of culprit lesion in UA/NSTEMI and might therefore serve as non-invasive determinants of the population that is at high risk for subsequent adverse events.

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. (Am Heart J 2001;141:566-72.)

Results of the Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy (TACTICS-TIMI 18) Trial: A Comparison of Invasive Versus Conservative Strategy in Patients With Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction

Background : In the treatment of patients with unstable angina and non-ST segment elevation myocardial infarction (UA/NSTEMI), debate exists as to whether an early invasive vs. a conservative strategy is optimal therapy. Methods: In the international TACTICS-TIMI 18 trial, 2220 patients with UA/NSTEMI who had either electrocardiographic changes, …