Low molecular weight heparin (enoxaparin) in the management of unstable angina: the ESSENCE study. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
K A Fox
Publications and source records attributed to K A Fox.
A quit smoking group. Pilot study.
1. While the rate of smoking is extremely high among persons with mental illness, there have been efforts to assist this population to quit. A 10-week smoking cessation program was provided for 10 highly nicotine dependent persons with persistent mental illness. 2. No significant differences were found in psychiatric symptoms or drug side effects prior to and after smoking cessation efforts. Four months later, for the 7 subjects who completed the program, 14% were abstinent, 43% maintained reduced tobacco intake, and 43% had resumed previous smoking patterns. 3. Specific barriers to quitting include a lack of nonsmoking coping skills, long-term identity as a smoker, ready access to tobacco products, nicotine addiction, and limited nonsmoking social support.
Adult↗
Heart rate variability and cardiac failure.
Explore the source record for details and available documents.
Adolescent↗
Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).
BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.
Aged↗
Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin versus intravenous unfractionated heparin, in non-Q-wave Coronary Events.
Combination antithrombotic therapy with heparin plus aspirin decreases the risk of recurrent ischemic events in patients with acute coronary syndromes without persistent ST-segment elevation. Compared with standard unfractionated heparin, low-molecular-weight heparin (LMWH) has a more predictable antithrombotic effect, is easier to administer, and does not require coagulation monitoring. At 176 hospitals in 3 continents, 3,171 patients with rest unstable angina or non-wave myocardial infarction were randomly assigned to either enoxaparin (a LMWH), 1 mg/kg twice daily subcutaneously, or to continuous intravenous unfractionated heparin, for a minimum of 48 hours to a maximum of 8 days. Trial medication was administered in a double-blind, placebo-controlled fashion. At 14 days, the primary endpoint, the composite risk of death, myocardial infarction, or recurrent angina with electrocardiographic changes or prompting intervention, was significantly lower in patients assigned to enoxaparin compared with heparin (16.6% vs 19.8%; odds ratio [OR] 1.24; 95% confidence interval [CI] 1.04-1.49; p = 0.019). At 30 days, the composite risk of death, myocardial infarction, or recurrent angina remained significantly lower in the enoxaparin group compared with the unfractionated heparin group (19.8% vs 23.3%, OR 1.23; 95% CI 1.0-1.46, p = 0.016). The rate of revascularization procedures at 30 days was also significantly lower in patients assigned to enoxaparin (27.1% vs 32.2%, p = 0.001). The 30-day incidence of major bleeding complication was 6.5% versus 7.0% (p = not significant), but the incidence of minor bleeding was significantly higher in the enoxaparin group (13.8% vs 8.8%, p <0.001) due primarily to injection-site ecchymosis. Thus, combination antithrombotic therapy with enoxaparin plus aspirin is more effective than unfractionated heparin plus aspirin in decreasing ischemic outcomes in patients with unstable angina or non-Q-wave myocardial infarction in the early (30 days) phase. The lower recurrent ischemic event rate seen with the LMWH, enoxaparin, is achieved without an increase in major bleeding, but with an increase in minor bleeding complications due mainly to injection-site ecchymosis.
Adolescent↗
Three-dimensional echocardiographic evaluation of left ventricular volume: comparison of Doppler myocardial imaging and standard gray-scale imaging with cineventriculography--an in vitro and in vivo study.
BACKGROUND: Standard gray-scale imaging (GSI), three-dimensional (3D) echocardiography has been shown to be superior to two-dimensional echocardiography in measuring left ventricular volume. However, the often relatively poor quality of transthoracic gray-scale data can limit the potential application of this technique. Doppler myocardial imaging (DMI) is a new ultrasound technique that potentially offers higher-quality 3D images with a transthoracic approach than the 3D GSI technique. This study was designed to compare the accuracy of standard GSI and DMI 3D left ventricular volume measurements in vitro and in vivo. METHODS AND RESULTS: In vitro, the minimum and maximum volume of the contracting single-chamber, tissue-mimicking phantom was calculated by using both techniques. In vivo, GSI and DMI 3D left ventricular volume measurements were performed in 16 patients. End-diastolic and end-systolic left ventricular volumes were computed for both techniques and compared with those calculated by cineventriculography. In vitro, both methods tended to underestimate the true phantom volume, but the systematic error was smaller for DMI than for GSI (-1.2% +/- 1.5% vs. -4.3% +/- 3%; p < 0.01) and was more constant in the case of DMI over the range of different sizes of true volume. In vivo, for GSI the end-diastolic volume mean difference was -12.6 ml and the limits of agreement were +/-18 ml, and for DMI the corresponding values were -4.2 and +/- 10.6 ml, respectively. The difference for end-systole was -6.5 +/- 10.6 ml and -1.5 +/- 10 ml for GSI and DMI, respectively. The magnitude of the difference in volume measurement between 3D echocardiography and cineventriculography was significantly smaller when using the Doppler technique. CONCLUSIONS: The results of this in vitro and in vivo study indicate that DMI is superior to GSI as a transthoracic acquisition technique for 3 D volume computation.
Echocardiography, Three-Dimensional↗
Safe use of platelet GP IIb/IIIa inhibitors.
The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used for the treatment of patients undergoing high-risk percutaneous coronary interventions and is used in approximately one third of coronary interventions in the United States and a growing number of procedures in Europe. Recent clinical trials have shown that this potent antiplatelet agent significantly reduces the incidence of death and nonfatal myocardial infarction and the need for revascularization. With expanding experience since the commercial release of abciximab in February 1995, several strategies to enhance the safety of abciximab have emerged. In particular, new data confirm that the risk of bleeding-identified as a concern in the original EPIC trial-can be substantially reduced through the use of low-dose adjunctive heparin, early sheath removal, and fastidious postprocedure vascular access site care. Other recommendations for enhancing the safety of potent antiplatelet agents in a variety of clinical situations are provided. The following article reflects insights regarding the safety of glycoprotein IIb/IIIa inhibitors expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997 This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.
Abciximab↗
The L-arginine/nitric oxide pathway contributes to the acute release of tissue plasminogen activator in vivo in man.
OBJECTIVE: Effective endogenous fibrinolysis requires rapid release of endothelial tissue plasminogen activator (t-PA). Using the nitric oxide synthase inhibitor, L-NG-monomethylarginine (L-NMMA), we examined the contribution of endogenous nitric oxide to substance P-induced t-PA release in vivo in man. METHODS: Blood flow and plasma fibrinolytic and haemostatic factors were measured in both forearms of 8 healthy male volunteers who received unilateral brachial artery infusions of substance P (2-8 pmol/min) and L-NMMA (1-4 micrograms/min). RESULTS: Substance P caused dose-dependent increases in blood flow (P < 0.001) and plasma t-PA antigen (P = 0.04) and activity (P < 0.001) concentrations confined to the infused forearm, but had no effect on plasminogen activator inhibitor type I (PAI-I) or von Willebrand factor concentrations. In the presence of L-NMMA, substance P again caused significant increases in blood flow (P < 0.001) and t-PA antigen (P = 0.003) and activity (P < 0.001) concentrations but these increases were significantly less than with substance P alone (P < 0.001, P = 0.05 and P < 0.01, respectively). L-NMMA alone significantly reduced blood flow in the infused arm, but had no measurable effect on t-PA or PAI-1 concentrations. CONCLUSIONS: The L-arginine/nitric oxide pathway contributes to substance P-induced t-PA release in vivo in man. This provides an important potential mechanism whereby endothelial dysfunction increases the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.
Adult↗
Prospective use of glycoprotein IIb/IIIa receptor blockers in the emergency department setting.
Platelets play a pivotal role in the pathophysiology of acute coronary syndromes (ACS) and thus are logical therapeutic targets for treatment of this disease process. Platelet glycoprotein (GP) IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet aggregation, have been proved to reduce the 30-day incidence of death, acute myocardial infarction (MI), and urgent revascularization in both high-risk and low-risk patients undergoing percutaneous intervention procedures. Three-year follow-up has indicated that these benefits appear durable. Recent large-scale randomized trials have demonstrated the value of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in patients with unstable angina or those with MI with non-Q-wave abnormalities who are receiving pharmacologic management. In addition, emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the list of indications for GP IIb/IIIa receptor antagonists expands to encompass the full spectrum of ACS, there is increasing interest in the potential use of these agents in the emergency department setting. The integration of GP IIb/IIIa receptor inhibitors into ED protocols will ultimately depend largely on whether these drugs prove to be safe and effective regardless of the direction of ST-segment deviation, and irrespective of whether definitive therapy will be invasive or conservative.
Acute Disease↗
Effect of DC shock on serum levels of total creatine kinase, MB-creatine kinase mass and troponin T.
After successful resuscitation from cardiac arrest, it is important to identify whether the event has been triggered by a myocardial infarction, since this determines subsequent investigations and management. Previous studies have shown that biochemical indices of infarction become elevated after resuscitation in patients without myocardial infarction. This can lead to overdiagnosis of myocardial infarction in the post-arrest setting. The cause of the elevated enzyme levels is not known, but may involve electrical or mechanical injury to the heart during resuscitation. In this study we aimed to identify the effects of isolated direct current shock on serum levels of creatine kinase (CK), MB creatine kinase mass (MB-CK), and troponin T, and examined the relationships between enzyme levels and the dose of electrical energy used. Thirteen patients were studied who underwent DC cardioversion for atrial fibrillation. Serum was obtained for CK, MB-CK and troponin T estimation before and 10 min after cardioversion, at hourly intervals for 8 h, and 18 h after cardioversion. Total serum CK became significantly elevated after only 3 h and rose to a peak of 1294.4 IU l(-1) (P < 0.02) at 18 h. Post-shock CK levels were strongly correlated with total shock energy (r = 0.8, P < 0.01). Serum MB-CK was significantly elevated at 18 h among patients receiving total shock energies greater than 1000 J than in those receiving lower doses, reflecting a positive correlation (r = 0.64, P < 0.05) between shock energy and peak MB-CK level. Troponin T levels were not significantly elevated after cardioversion. In conclusion, total serum CK levels become significantly elevated early after cardioversion, suggesting rapid wash-out from injured skeletal muscle. MB-CK levels become significantly elevated in individuals receiving high energy shocks, probably due to release of small quantities of the CK-MB isoform from skeletal muscle. The negligible troponin T levels seen after high energy cardioversion indicate that significant myocardial injury does not occur. Electrical injury is not likely to account for the elevated troponin T levels seen after out-of-hospital resuscitation in patients without myocardial infarction.
Aged↗
Reduced responsiveness to endothelin-1 in peripheral resistance vessels of patients with syndrome X.
OBJECTIVES: This study sought to assess the contribution and action of nitric oxide and endothelin-1 in peripheral resistance vessels of patients with syndrome X. BACKGROUND: Patients with syndrome X may have a generalized disorder of vascular and endothelial function, promoting vasospasm. METHODS: Changes in blood flow responses to intrabrachial infusion of the endothelium-dependent vasodilators substance P and acetylcholine, the endothelium-independent nitric oxide donor sodium nitroprusside and the endothelin type A (ET(A)) receptor antagonist BQ-123 were assessed using venous occlusion plethysmography in 10 patients with syndrome X and 10 matched control subjects. Vasoconstrictor responses to the nitric oxide synthase inhibitor L-N(G)-monomethyl arginine (L-NMMA) and endothelin-1 were also determined. RESULTS: There were no significant differences in the responses to acetylcholine, substance P, sodium nitroprusside or BQ-123 between patients and control subjects. However, despite similar degrees of vasoconstriction in response to L-NMMA in both groups, endothelin-1 caused a reduction in forearm blood flow of only 20 +/- 2% in patients with syndrome X compared with 35 +/- 3% in matched control subjects at 90 min (p < 0.001). Although plasma endothelin-1 concentrations were not significantly higher in patients with syndrome X (4.8 vs. 4.0 pg/ml, p = 0.17), the vasoconstriction caused by endothelin-1 infusion correlated inversely with plasma endothelin-1 concentrations (r = -0.51, p = 0.04). CONCLUSIONS: Patients with syndrome X had normal basal and stimulated nitric oxide activity and basal endogenous ET(A) receptor-mediated vascular tone. However, despite otherwise normal vascular function, there was reduced responsiveness to exogenous endothelin-1, possibly reflecting overactivity of this system and ET(A) receptor downregulation.
Analysis of Variance↗
Isosorbide dinitrate and furosemide in the treatment of patients with severe pulmonary edema.
Explore the source record for details and available documents.
Journal Article↗
Low molecular weight heparins in acute coronary syndromes.
Explore the source record for details and available documents.
Angina, Unstable↗
A 'same day' direct-access chest pain clinic: improved management and reduced hospitalization.
The aims of the Chest Pain Clinic were: to establish rapid-access, 'same-day', referral and attendance without a waiting list; to provide a diagnosis, treatment and follow-up plan for each patient; and to optimize the use of hospitalization for appropriate patients. Prospective data were collected from 1001 consecutive General Practitioner referrals to the Chest Pain Clinic over a 22-month period. Hospital admissions were reduced from an estimated 268 to 145 patients. Without a Chest Pain Clinic service, 213 (21%) would have been admitted inappropriately, and 89 (9%) with unstable angina or myocardial infarction would potentially have been managed in the community. A firm diagnosis was provided in 92% of cases (919 patients) with 42% (418) diagnosed as having ischaemic heart disease. The provision of a Chest Pain Clinic reduces the hospitalization of patients with benign non-cardiac chest pain whilst facilitating the identification of those patients with acute coronary syndromes requiring in-patient care. The Chest Pain Clinic service has a higher diagnostic yield for ischaemic heart disease than open access exercise electrocardiography, provides the General Practitioner with a firm clinical diagnosis in over 90% of cases, and identifies those patients requiring further treatment and invasive investigation.
Adult↗
Characterisation of coronary atherosclerotic morphology by spectral analysis of radiofrequency signal: in vitro intravascular ultrasound study with histological and radiological validation.
OBJECTIVE: To determine whether spectral analysis of unprocessed radiofrequency (RF) signal offers advantages over standard videodensitometric analysis in identifying the morphology of coronary atherosclerotic plaques. METHODS: 97 regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at 250 MHz. Two different sizes of ROI were identified from scan converted images, and relative amplitudes of different frequency components were analysed from raw data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth (17-42 MHz). RF images were constructed and compared with comparative histology derived from microscopy and radiological techniques in three dimensions. RESULTS: Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral slope was steeper in heavy calcium (-0.45 (0.1)) than in dense fibrotic tissue (-0.31 (0.1)), and maximum power was higher for heavy calcium (-7.7 (2.0)) than for dense fibrotic tissue (-10.2 (3.9)). Maximum power was significantly higher in heavy calcium (-7.7 (2.0) dB) and dense fibrotic tissue (-10.2 (3.9) dB) than in microcalcification (-13.9 (3.8) dB). Y-axis intercept was higher in microcalcification (-5.8 (1.1) dB) than in moderately fibrotic tissue (-11.9 (2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power: moderate -20.2 (1.1) dB, dense -14.7 (3.7) dB; and y-axis intercept: moderate -11.9 (2.0) dB, dense -5.5 (5.4) dB. Different densities of fibrosis, loose, moderate, and dense, were discriminated with both y-axis intercept, spectral slope, and mean power. Lipid could be differentiated from other types of plaque tissue on the basis of spectral slope, lipid -0.17 (0.08). Also y-axis intercept from lipid (-17.6 (3.9)) differed significantly from moderately fibrotic tissue, dense fibrotic tissue, microcalcification, and heavy calcium. No significant differences in any of the measured parameters were seen between the results obtained from small and large ROIs. CONCLUSION: Frequency based spectral analysis of unprocessed ultrasound signal may lead to accurate identification of atherosclerotic plaque morphology.
Calcinosis↗
Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II.
OBJECTIVE: To determine directly the contribution of angiotensin II to basal and sympathetically stimulated peripheral arteriolar tone in patients with heart failure. DESIGN: Parallel group comparison. SUBJECTS: Nine patients with New York Heart Association grade II-IV chronic heart failure, and age and sex matched controls. INTERVENTIONS: Forearm plethysmography, lower body negative pressure, local intra-arterial administration of losartan, angiotensin II, and noradrenaline, and estimation of plasma hormone concentrations. MAIN OUTCOME MEASURES: Forearm blood flow responses, plasma hormone concentrations. RESULTS: Baseline blood pressure, heart rate, and forearm blood flow did not differ between patients and controls. In comparison with the non-infused forearm, losartan did not affect basal forearm blood flow (95% confidence interval -5.5% to +7.3%) or sympathetically stimulated vasoconstriction in controls. However, the mean (SEM) blood flow in patients increased by 13(5)% and 26(7)% in response to 30 and 90 micrograms/min of losartan respectively (p < 0.001). Lower body negative pressure caused a reduction in forearm blood flow of 20(5)% in controls (p = 0.008) and 13(5)% (p = 0.08) in patients (p = 0.007, controls v patients). Blood flow at 90 micrograms/min of losartan correlated with plasma angiotensin II concentration (r = 0.77; p = 0.03). Responses to angiotensin II and noradrenaline did not differ between patients and controls. CONCLUSIONS: Losartan causes acute local peripheral arteriolar vasodilation in patients with heart failure but not in healthy control subjects. Endogenous angiotensin II directly contributes to basal peripheral arteriolar tone in patients with heart failure but does not augment sympathetically stimulated peripheral vascular tone.
Analysis of Variance↗
Safe use of platelet GP IIb/IIIa inhibitors.
The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used for the treatment of patients undergoing high-risk percutaneous coronary interventions and is used in approximately one third of coronary interventions in the United States and a growing number of procedures in Europe. Recent clinical trials have shown that this potent antiplatelet agent significantly reduces the incidence of death and nonfatal myocardial infarction and the need for revascularization. With expanding experience since the commercial release of abciximab in February 1995, several strategies to enhance the safety of abciximab have emerged. In particular, new data confirm that the risk of bleeding--identified as a concern in the original EPIC trial--can be substantially reduced through the use of low-dose adjunctive heparin, early sheath removal, and fastidious postprocedure vascular access site care. Other recommendations for enhancing the safety of potent antiplatelet agents in a variety of clinical situations are provided. The following article reflects insights regarding the safety of glycoprotein IIb/IIIa inhibitors expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.
Abciximab↗
Treatment options in unstable angina: a clinical update.
Treatment of unstable coronary artery disease with a combination of aspirin and intravenous heparin is now widely established but carries a significant failure rate, the origins of which lie in the fundamental characteristics of heparin and aspirin. The use of low-molecular-weight heparins (LMWHs) as an alternative to unfractionated heparin carries theoretical and practical advantages. Clinical trial evidence is now available to show that the LMWH enoxaparin, in a dosage of 1.0 mg x kg(-1) subcutaneously every 12 h for 2-8 days, is significantly more effective than unfractionated heparin, and that the benefits persist even after treatment ends. Ongoing trials will provide more efficacy data over both the short and the longer term. Enoxaparin at a dosage of 1.0 mg x kg(-1) every 12 h is as effective as higher doses but is associated with a much lower rate of major haemorrhage.
Angina, Unstable↗