Safety Of Subcutaneous Enoxaparin Research Articles

Validation of Bleeding Classifications in Coronary Artery Bypass Grafting

Perioperative bleeding is a determinant of poor outcome in patients undergoing coronary artery bypass grafting (CABG), but there is a lack of adequate stratification of its severity. The ability of the European registry of Coronary Artery Bypass Grafting (E-CABG), Universal Definition of Perioperative Bleeding (UDPB), Study of Platelet Inhibition and Patient Outcomes (PLATO), Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events-Seventh Organization to Assess Strategies in Ischemic Syndromes (CURRENT-OASIS 7), Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events (ESSENCE), and SafeTy and Efficacy of Enoxaparin in Percutaneous coronary intervention patients, an internationaL randomized Evaluation (STEEPLE) bleeding classifications to predict early mortality, stroke, acute kidney injury (AKI) stage 3, and deep sternal wound infection/mediastinitis was investigated in 3,730 patients from the prospective, multicentre E-CABG registry. Increasing grades of the E-CABG, UDPB, PLATO, and CURRENT-OASIS 7 classifications were associated with increasing risks of early mortality, had similar receiver-operating characteristic area under the curves (>0.7), and were predictive also when adjusted for EuroSCORE II. The E-CABG and UDPB classifications had satisfactory area under the curves (>0.6) in predicting stroke, AKI stage 3, and deep sternal wound infection/mediastinitis even when adjusted for EuroSCORE II. The PLATO and CURRENT-OASIS 7 classifications had similar predictive ability for stroke and AKI stage 3 as confirmed by multivariate analysis adjusted for EuroSCORE II but showed inferior ability in predicting severe wound infection compared to the E-CABG and UDPB classifications. The STEEPLE and ESSENCE classifications had a poor ability of predicting all these adverse events. Decision curve analysis showed a benefit of the E-CABG bleeding classification over the other classifications in predicting alladverse events. In conclusion, the E-CABG, UDPB, PLATO, and CURRENT-OASIS 7bleeding classifications have a satisfactory ability in predicting adverse events afterCABG. Decision curve analysis showed that the E-CABG bleeding classification had the best predictive performance.

Standard medical care of patients with systemic lupus erythematosus (SLE) in large specialised centres: data from the Russian Federation, Ukraine and Republic of Kazakhstan (ESSENCE)

ObjectivesTo describe disease characteristics and treatment regimens for adult patients with systemic lupus erythematosus (SLE) with autoantibody positive disease in three countries (the Russian Federation, Ukraine and Republic of Kazakhstan).MethodsThe...

Safety of subcutaneous enoxaparin as ancillary therapy in STEMI patients receiving fibrinolysis

Safety of subcutaneous enoxaparin as ancillary therapy in STEMI patients receiving fibrinolysis

Comparison of Safety of Subcutaneous Enoxaparin as Outpatient Anticoagulation Bridging Therapy in Patients With a Mechanical Heart Valve Versus Patients With Nonvalvular Atrial Fibrillation

Comparison of Safety of Subcutaneous Enoxaparin as Outpatient Anticoagulation Bridging Therapy in Patients With a Mechanical Heart Valve Versus Patients With Nonvalvular Atrial Fibrillation

Clinical Risk Stratification in the Emergency Department Predicts Long-Term Cardiovascular Outcomes in a Population-Based Cohort Presenting With Acute Chest Pain

The long-term cardiovascular outcomes of a population-based cohort presenting to the emergency department (ED) with chest pain and classified with a clinical risk stratification algorithm are not well documented. The Olmsted County Chest Pain Study is a community-based study that included all consecutive patients presenting with chest pain consistent with unstable angina presenting to all EDs in Olmsted County, Minnesota. Patients were classified according to the Agency for Health Care Policy and Research (AHCPR) criteria. Patients with ST elevation myocardial infarction and chest pain of noncardiac origin were excluded. Main outcome measures were major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days and at a median follow-up of 7.3 years, and mortality through a median of 16.6 years.The 2271 patients were classified as follows: 436 (19.2%) as high risk, 1557 (68.6%) as intermediate risk, and 278 (12.2%) as low risk. Thirty-day MACCE occurred in 11.5% in the high-risk group, 6.2% in the intermediate-risk group, and 2.5% in the low-risk group (p < 0.001). At 7.3 years, significantly more MACCE were recorded in the intermediate-risk (hazard ratio [HR], 1.91; 95% confidence intervals [CI], 1.33-2.75) and high-risk groups (HR, 2.45; 95% CI, 1.67-3.58). Intermediate- and high-risk patients demonstrated a 1.38-fold (95% CI, 0.95-2.01; p = 0.09) and a 1.68-fold (95% CI, 1.13-2.50; p = 0.011) higher mortality, respectively, compared to low-risk patients at 16.6 years. At 7.3 and at 16.6 years of follow-up, biomarkers were not incrementally predictive of cardiovascular risk.In conclusion, a widely applicable rapid clinical algorithm using AHCPR criteria can reliably predict long-term mortality and cardiovascular outcomes. This algorithm, when applied in the ED, affords an excellent opportunity to identify patients who might benefit from a more aggressive cardiovascular risk factor management strategy.

Comparison of Effectiveness of Enoxaparin Versus Unfractionated Heparin to Reduce Silent and Clinically Apparent Acute Myocardial Infarction in Patients Presenting With Non–ST-Segment Elevation Acute Coronary Syndrome

Electrocardiographic (ECG) estimates of myocardial infarct size based on the Selvester ECG score have been shown to predict mortality and left ventricular function after acute myocardial infarction (AMI). This score has also been used to identify not clinically apparent AMI ("silent" AMI) and to determine treatment effect, suggesting it could serve as a clinical trial end point. The objective of this study was to compare the rate of silent AMI as measured by the Selvester QRS score in patients with a non-ST-segment elevation acute coronary syndrome treated with enoxaparin versus intravenous unfractionated heparin who were participating in a continuous ECG monitoring substudy of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events study (ESSENCE) and INTegrelin and Enoxaparin Randomized Assessment of acute Coronary syndrome Treatment trial (INTERACT). Enoxaparin was associated with a 56% relative risk decrease in silent AMI at 96 hours compared with unfractionated heparin (2.7% vs 6.1% p = 0.03). Similarly, enoxaparin decreased Holter-detected myocardial ischemia compared with unfractionated heparin (18.7% vs 35.9%, p = 0.03). In conclusion, enoxaparin significantly decreased the composite of silent AMI or clinical AMI and death at 1 year (9.3% vs 21%, p = 0.0001).

Recurrent cardiac ischemic events early after discontinuation of short-term heparin treatment in acute coronary syndromes: Results from the thrombolysis in myocardial infarction (TIMI) 11B and efficacy and safety of subcutaneous enoxaparin in Non–Q-Wave coronary events (ESSENCE) studies

ObjectivesThe aim of this study was to determine whether discontinuation of low-molecular-weight heparin (LMWH) treatment results in a clustering of cardiac ischemic events as previously observed after cessation of unfractionated heparin (UFH) in acute coronary syndrome (ACS) patients. BackgroundClinical trials in patients with ACS have shown early recurrent ischemic events after discontinuation of UFH treatment. We analyzed whether LMWH cessation also results in early ischemic recurrence events and if continuation of a fixed-dose LMWH prevents this complication. MethodsThe combined incidence of death, myocardial infarction, or urgent revascularization in the first seven days after discontinuation of UFH (n = 3,012), short-term enoxaparin 1 mg/kg subcutaneously twice a day (n = 2,011), and short-term enoxaparin followed by prolonged enoxaparin 60 mg subcutaneously twice a day (n = 1,075) was analyzed from the combined Thrombolysis In Myocardial Infarction (TIMI) 11B/Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events (ESSENCE) database in a per patient analysis. ResultsThe cessation of both UFH and short-term enoxaparin resulted in a similar clustering of recurrent ischemic events on the first day, with an incidence of the primary end point of 2.8% in both groups. Of all recurrent events in the first week after cessation, 40% occurred in the first 24 h. The continuation of a fixed-dose enoxaparin treatment prevented this early excess, with a first day incidence of 0.4% (p < 0.0001). The TIMI risk score characteristics predicted the incidence of early rebound ischemic events. ConclusionsThere is significant clustering of recurrent ischemic events within 24 h after cessation of both short-term UFH and enoxaparin treatment, and patients should be carefully monitored during that period. This early rebound may be prevented by continuation of a fixed dose of enoxaparin.

Enoxaparin in unstable angina patients who would have been excluded from randomized pivotal trials

ObjectivesIn the present study, we describe the characteristics and examine the anticoagulation levels and safety of subcutaneous enoxaparin in unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI) patients who would not have been eligible in the Efficacy Safety Subcutaneous Enoxaparin in Non–Q-wave Coronary Events (ESSENCE) and Thrombolysis In Myocardial Infarction (TIMI)-11B trials. BackgroundIt is not known whether the benefit shown with enoxaparin in the selected population of pivotal trials can be extended to the real world. MethodsIn our center, all patients with UA/NSTEMI are anticoagulated with subcutaneous enoxaparin adjusted to creatinine clearance. Among 515 consecutive patients, we identified 174 who would not have been eligible for ESSENCE or TIMI-11B (“EP” group for excluded patients). We evaluated cardiovascular death or non-fatal myocardial infarction (MI), as well as major and minor bleeding events, at 30 days in the EP group and in patients without any of the exclusion criteria (“NEP” group for non-excluded patients). ResultsThis EP group was older, had a higher female/male ratio, and more frequently had a history of MI or a diagnosis of non-Q MI on admission than the NEP group. The distribution of the anti-Xa activity was similar in both groups. The bleeding rates (major and minor) at 30 days were similar in the EP and NEP groups (2.3% vs. 2.9%, respectively, p = NS). On multivariate analysis, the use of glycoprotein IIb/IIIa inhibitors and the presence of hypertension were the only independent predictors of bleeding found in the whole population. Compared with the NEP group, the EP group had a fourfold increased rate of death or MI at 30 days (15.5% vs. 4.1%, p < 0.01). On multivariate analysis, the independent predictors of death or MI at 30 days were NSTEMI on admission, creatinine clearance, and heart failure. ConclusionsPatients who do not fit the enrollment criteria of ESSENCE/TIMI-11B have higher risk baseline characteristics for both bleeding and ischemic events. In these patients, enoxaparin with dose adjustment to creatinine clearance provides adequate anti-Xa levels and no excess of bleeding.

Comparison of enoxaparin versus unfractionated heparin in patients with unstable angina pectoris/non–ST-segment elevation acute myocardial infarction having subsequent percutaneous coronary intervention

Patients with unstable angina or non–ST-segment elevation myocardial infarction (MI) may undergo invasive revascularization procedures shortly after admission to hospital or after a brief period of stabilization. In the Thrombolysis In Myocardial Infarction (TIMI) 11B trial and Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events (ESSENCE) trial 1,326 patients underwent percutaneous coronary intervention (PCI). A total of 924 patients underwent PCI during the initial hospitalization period, and of these, 445 patients did so while receiving treatment with unfractionated heparin (UFH) or the low-molecular-weight heparin, enoxaparin. This analysis compared efficacy and clinical events in the enoxaparin and UFH groups in patients who: (1) underwent PCI while on treatment versus those who did not, and (2) underwent PCI in hospital. We also compared those who did not undergo PCI. Treatment with enoxaparin (1 mg/kg given as twice daily subcutaneous injections) was beneficial and well tolerated in patients with unstable angina and non–ST-segment elevation MI who underwent PCI. Compared with UFH, enoxaparin significantly reduced the likelihood of clinical events (death and nonfatal MI after PCI) in patients who underwent PCI after 1 year (p = 0.003 for in-hospital PCI; p = 0.005 for on-treatment PCI), with a trend toward a reduced event rate at 43 days. In addition, patients treated with enoxaparin who did not undergo PCI also showed a reduction in the risk of death, nonfatal MI, and urgent revascularization when compared with those treated with UFH (significant at 43 days, with a trend persisting at 1 year). Study limitations were that PCI was nonrandomized, the analysis was post hoc, and the sample size was relatively small. Nevertheless, in the absence of large clinical trials, this study suggests that treatment with enoxaparin was well tolerated, and exhibited a similar risk of major hemorrhage to UFH in patients who underwent PCI.

Validation of the Thrombolysis In Myocardial Infarction (TIMI) risk score for unstable angina pectoris and non–ST-elevation myocardial infarction in the TIMI III registry

The 1.4 million patients admitted with unstable angina pectoris and non‐ST-elevation myocardial infarction (UAP/NSTEMI) each year are a heterogenous population with varying risks of death and recurrent cardiac events. The Thrombolysis In Myocardial Infarction (TIMI) risk score for UAP/NSTEMI was created to better stratify patients according to easily obtainable information gathered from the initial history, electrocardiogram, and cardiac markers. 1 The TIMI risk score was derived and validated in the TIMI 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Non‐Q-wave Coronary Events (ESSENCE) trials and accurately predicted adverse outcomes through 14 days. It has also been applied in the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) and Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)-TIMI 18 Trials. 2,3 However, because clinical trials of UAP/ NSTEMI usually select higher risk patients (with electrocardiographic changes and/or positive cardiac markers), there has been questions whether the TIMI risk score would be valid in an unselected population of patients representative of general clinical practice. The goal of this study was to validate the TIMI risk score in a large unselected population of patients with UAP/NSTEMI and assess its long-term predictive value. ••• The details of the TIMI III Registry have been previously reported. 4 Briefly, patients admitted be

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.)

The SYNERGY trial: Study design and rationale

Background Enoxaparin was shown to be superior to unfractionated heparin in the patients with non-ST-segment elevation acute coronary syndromes (ACS) in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events study and the Thrombolysis In Myocardial Infarction (TIMI) 11B trial. However, enoxaparin has had limited acceptance in clinical practice, in part because of the contemporary management of these patients, which includes glycoprotein IIb/IIIa inhibition and the use of early invasive management strategies. Study Design The Superior Yield of the New strategy of Enoxaparin, Revascularization and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) trial is an 8000-patient, prospective, randomized, open-label, multicenter investigation of enoxaparin compared with unfractionated heparin in patients at high risk with non-ST-segment elevation ACS treated with an early invasive strategy. The primary efficacy end point is death or nonfatal myocardial infarction 30 days after enrollment. Implications The SYNERGY trial is the largest study currently planned for the acute therapy of patients with non-ST-segment elevation ACS and the first large trial since the publication of the revised American College of Cardiology/American Heart Association guidelines for the management of these patients. In addition to evaluating the potential superiority of enoxaparin over unfractionated heparin, this investigation will provide important observations of current treatment strategies in patients with ACS. (Am Heart J 2002;143:952-60.)

Enoxaparin: a pharmacoeconomic review of its use in the prevention and treatment of venous thromboembolism and in acute coronary syndromes.

The pharmacoeconomics of the low molecular weight heparin (LMWH) enoxaparin in the prophylaxis and treatment of venous thromboembolism have mostly been investigated in cost-effectiveness studies that estimated direct costs associated with treatment, using decision analyses and clinical outcome data from randomised controlled trials. These studies have shown enoxaparin to be cost effective compared with unfractionated heparin (UFH) and warfarin in short-term thromboprophylaxis for hospital inpatients undergoing orthopaedic surgery and in thromboprophylaxis following trauma. Outpatient treatment of acute proximal deep vein thrombosis with enoxaparin has also been shown to be cost effective compared with inpatient treatment using UFH. In general surgery, however, it remains to be determined whether enoxaparin is a cost-effective alternative to UFH. The cost effectiveness of enoxaparin compared with UFH in the treatment of unstable angina and non-Q-wave myocardial infarction has also been investigated in several countries using clinical outcomes data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) randomised trial. ESSENCE demonstrated that enoxaparin was superior to UFH in terms of tolerability and efficacy, and cost saving at both 30-day and 1-year follow-ups. An increasing number of studies indicate enoxaparin to be of economic benefit when used for prevention and treatment of venous thromboembolism and treatment of acute coronary symdromes.

Enoxaparin: an update of its clinical use in the management of acute coronary syndromes.

Enoxaparin (enoxaparin sodium) is a low molecular weight heparin (LMWH) indicated for use in the treatment of ischaemic complications of unstable angina and non-Q wave myocardial infarction (MI). Unfractionated heparin (UFH) has for many years represented the standard in anticoagulant therapy for patients with acute coronary syndromes; however, recent studies suggest that enoxaparin is also a viable option for anticoagulant therapy in these patients. The ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events) and the TIMI 11B (Thrombolysis in Myocardial Infarction) studies reported that twice daily enoxaparin was significantly more effective than a continuous infusion of UFH in reducing the composite triple endpoint of death, MI, or recurrent angina or urgent revascularisation. Follow-up of both patient populations showed continued benefit associated with enoxaparin. Enoxaparin has been compared with tinzaparin in the treatment of unstable coronary artery disease using a nonblind study design. There was no difference between treatment groups in the therapeutic endpoints. Three nonblind studies have also compared the effects of enoxaparin and UFH in patients receiving thrombolytic therapy following acute MI. The HART II (Heparin and Aspirin Reperfusion Therapy), the ASSENT 3 (Assessment of the Safety and Efficacy of a New Thrombolytic Regimen) and the ENTIRE-TIMI 23 (Enoxaparin and Tenecteplase with or without glycoprotein IIb/IIIa Inhibitor as Reperfusion strategy in ST Elevation MI - Thrombolysis in Myocardial Infarction) studies have revealed that enoxaparin in combination with alteplase or tenecteplase is at least equivalent (HART II and ENTIRE-TIMI 23), and possibly superior (ASSENT 3) to UFH. Enoxaparin is administered as a twice-daily subcutaneous injection. In contrast, UFH is administered as an intravenous infusion which requires routine monitoring of the activated partial thromboplastin time to ensure adequate levels of anticoagulation are maintained. During the acute phase of the the ESSENCE and TIMI 11B studies, the incidence of major bleeding was similar in patients receiving enoxaparin to that in patients receiving UFH. In contrast, the rates of minor bleeding were higher in patients receiving enoxaparin than in those receiving UFH throughout these studies. Data from the ESSENCE, TIMI 11B and ASSENT 3 studies have prompted calls for those LMWHs which have been shown to be superior to UFH, to be considered as first choice treatment for anticoagulation in unstable coronary syndromes. To date, these suggestions are not reflected in current guidelines which consider UFH and LMWHs equally. Irrespective, the clinical data reported in this review support the use of enoxaparin in the treatment of acute coronary syndromes. These data suggest that enoxaparin shows certain clinical and practical advantages over standard treatment with UFH and represents an important development in the treatment of acute coronary syndromes.

Prospective comparison of hemorrhagic complications after treatment with enoxaparin versus unfractionated heparin for unstable angina pectoris or non–ST-segment elevation acute myocardial infarction

Patients with unstable angina pectoris (UAP) or non–ST-segment elevation acute myocardial infarction (AMI) are at risk of death or recurrent ischemic events, despite receiving aspirin and unfractionated heparin (UFH). This study investigates the effect of the low molecular weight heparin, enoxaparin, on the incidence of hemorrhage and thrombocytopenia in relation to baseline characteristics and subsequent invasive procedures. Rates of hemorrhage and thrombocytopenia were analyzed for UAP or non–ST-segment elevation AMI in patients included in the prospective, randomized, double-blind Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events (ESSENCE) study. Patients received either enoxaparin or UFH, plus aspirin, for 2 to 8 days. The overall rate of major hemorrhage (at 30 days) was comparable between the 2 groups (6.5% for enoxaparin vs 7.0% for UFH, p = 0.6). The rate of major hemorrhage while on treatment was slightly higher in the enoxaparin group, but this was not significant (1.1% vs 0.7% for UFH, p = 0.204), as was the rate of major hemorrhage within 48 hours of coronary artery bypass grafting performed within 12 hours of treatment. However, the rate of minor hemorrhage was significantly higher in the enoxaparin group, with the majority being injection-site ecchymoses or hematomas (11.9% vs 7.2% with UFH, p <0.001). Thrombocytopenia (platelet count <100,000 per mm3) occurred mainly in association with coronary bypass surgery, with a similar rate in both groups. Thus, enoxaparin is a well-tolerated alternative to UFH in the management of UAP or non–ST-segment elevation AMI. Despite the more effective antithrombotic effect, which results in fewer ischemic events, enoxaparin is not associated with an increase in the rate of major hemorrhagic complications, and is not significantly associated with thrombocytopenia, but is associated with an increase in minor injection site ecchymosis.

Prior aspirin use in unstable angina predisposes to higher risk: the aspirin paradox

Background: Aspirin is the most widely prescribed agent used in prevention of coronary thrombosis. Thus, many patients presenting with acute coronary syndromes have a history of aspirin usage. Methods: To assess response to medical therapy in patients taking aspirin prior to admission with an acute coronary syndrome, we reviewed outcomes data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) studies. Results: Patients with acute coronary syndromes who had taken aspirin prior to enrolment were less likely to have non-Q-wave myocardial infarction on admission (ESSENCE: 16.0% vs. 29.2%, p<0.001; PRISM-PLUS: 34.2% vs. 57.7%, p<0.001). However, prior aspirin users were more likely to be failed by standard medical therapy with unfractionated heparin than non-prior aspirin users (ESSENCE: 21.5% vs. 16.5%, p=0.017; PRISM-PLUS: 23.5% vs. 12.1%, p<0.001). Prior aspirin users received greater benefit from both enoxaparin (21.5% vs. 16.8%, p=0.009) and tirofiban with unfractionated heparin (23.5% vs. 16.0%, p=0.007) than from unfractionated heparin alone. Non-prior aspirin users presented with higher rates of non-Q-wave myocardial infarction. Conclusions: Prior aspirin users admitted with acute coronary syndromes may have a more benign presentation, but are more likely to be failed by medical therapy with unfractionated heparin and should be considered as a high-risk group. Enoxaparin or the combination of tirofiban and unfractionated heparin are both more effective than unfractionated heparin in this group.

Massive upper gastrointestinal bleed secondary to insertion of nasogastric tube

Electrocardiographic (ECG) estimates of myocardial infarct size based on the Selvester ECG score have been shown to predict mortality and left ventricular function after acute myocardial infarction (AMI). This score has also been used to identify not clinically apparent AMI (“silent” AMI) and to determine treatment effect, suggesting it could serve as a clinical trial end point. The objective of this study was to compare the rate of silent AMI as measured by the Selvester QRS score in patients with a non–ST-segment elevation acute coronary syndrome treated with enoxaparin versus intravenous unfractionated heparin who were participating in a continuous ECG monitoring substudy of the Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events study (ESSENCE) and INTegrelin and Enoxaparin Randomized Assessment of acute Coronary syndrome Treatment trial (INTERACT). Enoxaparin was associated with a 56% relative risk decrease in silent AMI at 96 hours compared with unfractionated heparin (2.7% vs 6.1% p = 0.03). Similarly, enoxaparin decreased Holter-detected myocardial ischemia compared with unfractionated heparin (18.7% vs 35.9%, p = 0.03). In conclusion, enoxaparin significantly decreased the composite of silent AMI or clinical AMI and death at 1 year (9.3% vs 21%, p = 0.0001).

Antithrombotic therapy in acute coronary syndromes: Key notes from ESSENCE and TIMI 11B

Platelet activation and thrombus formation are key events in the pathogenesis of acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction). Therefore, current management of these conditions consists of antithrombotic and antiplatelet therapy, principally heparin and oral aspirin. However, such treatment is unsuccessful in a significant proportion of patients. Two recent large studies with the low-molecular-weight heparin (LMWH) enoxaparin have shown that this agent significantly reduces the risk of major ischemic events compared with unfractionated heparin. In the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) study, treatment with enoxaparin for 2 to 8 days reduced the risk of death, myocardial infarction, or recurrent angina by 20% at 14 days compared with treatment with unfractionated heparin. In the Thrombolysis in Myocardial Infarction (TIMI) 11B study, enoxaparin was associated with a significant reduction in the risk of death, myocardial infarction, or urgent revascularization compared with unfractionated heparin, which became apparent within 48 hours; this benefit was maintained during outpatient treatment for 5 weeks. A meta-analysis of these two studies showed that the risk of death or myocardial infarction was consistently approximately 20% lower in enoxaparin-treated patients than in heparin-treated patients. In contrast, studies with other LMWHs have not shown consistent superiority over unfractionated heparin. This may reflect the pharmacologic heterogeneity of LMWH and/or differences in trial design.

Elderly Patients with Acute Coronary Syndromes: Higher Risk and Greater Benefit from Antithrombotic and Interventional Therapies.

In elderly patients with acute coronary syndromes, outcomes are poorer than in younger patients and, disappointingly, some therapies-including thrombolysis for ST elevation myocardial infarction-confer less benefit than in younger patients. In contrast, in unstable angina and non-ST elevation myocardial infarction, the elderly appear to derive greater relative and absolute benefit from the newer, more potent antithrombotic therapies. In both the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events and Thrombolysis in Myocardial Infarction 11B trials, the low molecular weight heparin enoxaparin, compared with unfractionated heparin, appeared to have greater relative and absolute benefit in patients aged 65 years and older, as compared with younger patients. For the glycoprotein IIb/IIIa inhibitors, an equivalent relative benefit has been observed, which translated into a greater absolute benefit in older vs. younger patients. Similarly, in the FRagmin and Fast Revascularisation during InStability in Coronary Artery Disease II trial, patients 65 years and older derived significantly greater benefit from an invasive than from a conservative strategy, whereas there was no difference in outcome by strategy in younger patients. A similar trend was observed in the Thrombolysis in Myocardial Infarction IIIB trial. Thus, in unstable angina and non-ST elevation myocardial infarction, elderly patients are at higher risk and appear to derive particular benefit from the more aggressive antithrombotic and interventional therapies. (c) 2000 by CVRR, Inc.

Inter-regional differences and outcome in unstable angina; analysis of the international ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events.

Worldwide there is a large variation in outcome (death, myocardial infarction and recurrent myocardial infarction) in patients with unstable angina or non-Q wave myocardial infarction. These variations may be explained by differences in characteristics of the presenting patients. Here we describe differences in patient presentation, treatment protocols and outcome and we investigate their relationship using data from the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) trial. A total of 2981 patients from six countries which enrolled more than 100 patients were included in the present analysis: United States, Canada, Argentina, France, the Netherlands and United Kingdom. Logistic regression analysis was performed to determine the effect of baseline characteristics on regional outcome. At day 30, the lowest triple end-point rate, irrespective of study drug treatment, was noted in the Netherlands (18.9%) and the highest in Argentina (30.5%). A model including the variables age > or = 65 years, prior angina, diabetes, prior aspirin use, ECG changes at baseline and diagnosis of non-Q wave myocardial infarction and dummy variables for Argentina and France resulted in concordance of about 60%. Inter-regional differences in outcome in unstable angina and non-Q wave myocardial infarction patients can reasonably well be explained by differences in patient characteristics. However, other so far unidentified variables present in Argentina and France also contributed to differences in outcome and their effect warrants further investigation.