Biomedical subjects

Harvey D White

Publications and source records attributed to Harvey D White.

At least 19 recordsLinked to original sources

PubMed2007

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

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

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PubMed2007

Antiplatelet therapy and progression of coronary artery disease: a placebo-controlled trial with angiographic and clinical follow-up after myocardial infarction.

INTRODUCTION: In patients after ST-elevation myocardial infarction (STEMI), antiplatelet therapy reduces subsequent cardiac events, which are often attributed to recurrent thrombosis with (sub)total occlusion in the infarct-related artery. Whether antiplatelet therapy influences the often subclinical process of coronary disease progression in noninfarct arteries has not been reported. METHODS: Quantitative coronary angiography of noninfarct arteries was performed on paired cine-angiograms of 149 patients from fibrinolytic trials who had a patent infarct-related artery 3 to 4 weeks following STEMI and who were randomized to either continue the daily combination of 50-mg aspirin and 400-mg dipyridamole or to matching placebo. Follow-up angiography was scheduled at 1 year. RESULTS: On a per-patient basis, the change in minimal luminal diameter (MLD) was 0.00 mm in the aspirin/dipyridamole group (n = 76) and was 0.01 mm in the placebo group (n = 73). There was no difference between these groups in the changes in MLD (-0.02 mm; 95% CI -0.09 to 0.05), neither were there significant differences in mean luminal diameter and diameter stenosis. Progression (1 segment/patient with > or = 0.40 mm decrease in MLD) was seen in two thirds of patients and did not independently predict long-term death and/or reinfarction. CONCLUSION: In this placebo-controlled trial after STEMI, the combination of aspirin and dipyridamole did not affect noninfarct artery disease progression. Progression did not predict long-term clinical outcome.

Aspirin↗

PubMed2007

Carvedilol: use in chronic heart failure.

Carvedilol is a beta-adrenergic antagonist with vasodilatory properties (alpha1-antagonism), which has been extensively evaluated in the treatment of patients with heart failure. In patients with chronic heart failure carvedilol improves left-ventricular (LV) ejection fraction over 6 to 12 months of treatment, and attenuates LV remodelling. Large-scale randomised, placebo controlled trials involving more than 4000 patients with chronic heart failure have demonstrated that carvedilol improves survival and reduces hospitalizations. Comparative studies with metoprolol in patients with heart failure have suggested that carvedilol may be associated with greater survival benefit although differences in the preparation of metoprolol have left uncertainty in this area. Carvedilol has a high safety profile and the clinical benefits appear maintained across a wide range of patients with comorbidities such as diabetes and renal failure. Carvedilol has also been shown to attenuate LV remodeling and improve clinical outcomes in patients with LV dysfunction and/or heart failure following acute myocardial infarction. As a result of these data, carvedilol is recommended for treatment of patients with heart failure in heart-failure guidelines. This evidence-based treatment should be widely implemented to ensure that patients with heart failure receive appropriate medical therapy.

Adrenergic beta-Antagonists↗

PubMed2006

Bivalirudin for patients with acute coronary syndromes.

BACKGROUND: Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. METHODS: We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. RESULTS: Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P=0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). CONCLUSIONS: In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158 [ClinicalTrials.gov].).

Adult↗

PubMed2006

The impact of anthropomorphic indices on clinical outcomes in patients with acute ST-elevation myocardial infarction.

AIMS: Multiple studies have focused on the relationship of body anthropometric measures with clinical events in ST-elevation myocardial infarction (STEMI) patients, highlighting the 'obesity paradox'. However, the relative prognostic importance of these measures over other baseline variables is less known. METHOD AND RESULTS: We performed a retrospective analysis of 94,108 STEMI patients from seven clinical trials evaluating various reperfusion strategies to study the relationship and prognostic importance of height, weight, body mass index (BMI), and body surface area (BSA) with 30-day death and in-hospital cardiogenic shock, major bleeding, and stroke. Main outcome measures of interest included 30-day death and in-hospital cardiogenic shock, major bleeding, and stroke. Weight, BMI, and BSA were inversely and independently related to all clinical events. Despite being statistically significant (P<0.0001), the prognostic information contributed by weight beyond that conferred by baseline clinical factors was minimal (<1% of total prognostic information) making it of limited clinical relevance for predicting 30-day death and cardiogenic shock. In contrast, weight accounted for 8.4% and 4.3% of the prognostic information in the logistic regression models for major bleeding and for stroke. BMI or BSA added little incremental value over simple measure of weight. CONCLUSION: Although statistically significantly related to most outcomes in patients with STEMI including death and shock, body weight provided clinically relevant prognostic information only for the risk of major bleeding and of stroke. Furthermore, BMI or BSA contributed little incremental prognostic information beyond that provided by weight alone. Thus, the existing large body of information concerning the strong prognostic importance of anthropometric measures with outcomes after STEMI should be interpreted in the context of other more important risk factors.

Body Height↗

PubMed2006

Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT Trial.

AIMS: We sought to determine risk models for predicting early and late stroke in a large cohort of high-risk post-myocardial infarction (MI) patients. METHODS AND RESULTS: We prospectively analysed data from 14 703 patients in the VALIANT trial with acute MI complicated by heart failure, left ventricular (LV) systolic dysfunction, or both. Patients were randomized 0.5-10 days after acute MI to valsartan, captopril, or their combination. We evaluated risk factors for early (<45 days) and late (>45 days) stroke by using multivariable Cox proportional hazards regression analyses with stepwise variable selection techniques applied to 92 pre-specified potential predictor variables. After randomization, 463 (3.2%) patients had fatal (n = 124) or non-fatal (n = 339) strokes, with 134 strokes occurring in the first 45 days. The strokes were classified as ischaemic (348), haemorrhagic (40), or of indeterminate cause (75). Estimated glomerular filtration rate and heart rate when in sinus rhythm were the most powerful predictors of early stroke (<45 days after MI), whereas diastolic blood pressure (DBP) >90 mmHg, prior stroke, and atrial fibrillation (AF) were the most powerful predictors of stroke overall. Ejection fraction and sex were not predictive of stroke in this cohort. CONCLUSION: Among high-risk patients presenting with MI but without initial neurological symptoms, the risk of stroke 6 weeks thereafter is 0.94% (95% CI 0.78-1.09). Of the most powerful baseline predictors of stroke, DBP and AF are amenable to therapeutic interventions and thus merit special attention in these patients.

Aged↗

PubMed2006

A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes.

OBJECTIVES: The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial. BACKGROUND: The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment. METHODS: Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days. RESULTS: After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding. CONCLUSIONS: Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.

Aged↗

PubMed2006

Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention.

BACKGROUND: Despite its limitations, unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). Several small studies have suggested that intravenous enoxaparin may be a safe and effective alternative. Our primary aim was to assess the safety of enoxaparin as compared with that of unfractionated heparin in elective PCI. METHODS: In this prospective, open-label, multicenter, randomized trial, we randomly assigned 3528 patients with PCI to receive enoxaparin (0.5 or 0.75 mg per kilogram of body weight) or unfractionated heparin adjusted for activated clotting time, stratified according to the use or nonuse of glycoprotein IIb/IIIa inhibitors. The primary end point was the incidence of major or minor bleeding that was not related to coronary-artery bypass grafting. The main secondary end point was the percentage of patients in whom the target anticoagulation levels were reached. RESULTS: Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non-CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, -2.6; 95% confidence interval [CI], -4.7 to -0.6; P=0.01), but the higher enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, -2.0; 95% CI, -4.0 to 0.0; P=0.051). The incidence of major bleeding was significantly reduced in both enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mg-per-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001). CONCLUSIONS: In elective PCI, a single intravenous bolus of 0.5 mg of enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844 [ClinicalTrials.gov].).

Aged↗

PubMed2006

Risk stratification of patients with acute anterior myocardial infarction and right bundle-branch block: importance of QRS duration and early ST-segment resolution after fibrinolytic therapy.

BACKGROUND: Patients with an acute anterior ST-segment elevation myocardial infarction and right bundle-branch block (RBBB) have a high mortality risk, which may be stratified by early ECG changes. METHODS AND RESULTS: In the Hirulog Early Reperfusion Occlusion (HERO-2) trial, 17 073 patients with acute myocardial infarction (AMI) within 6 hours of symptom onset were treated with streptokinase and randomized to receive bivalirudin or heparin. There was no difference in the primary end point of 30-day mortality. ECGs were recorded at randomization and 60 minutes after fibrinolytic therapy was begun. The 30-day mortality rate was 31.6% in the 415 patients with RBBB and anterior AMI at randomization and 33% in the 100 patients who developed new RBBB at 60 minutes from normal baseline conduction accompanying an anterior AMI. An increase in QRS duration by 20-ms increments was associated with increasing 30-day mortality rate in both RBBB groups on multivariable analyses with covariates of age, Killip class, systolic blood pressure, pulse, and prior infarction. Patients with QRS duration > or = 160 ms had higher 30-day mortality rate than those with QRS duration < 160 ms (37.2% versus 27.2%, P = 0.03, and 46.2% versus 24.5%, P = 0.025, in the 2 groups, respectively). For the patients with RBBB and anterior MI at randomization, RBBB resolved at 60 minutes in 40 patients, but 30-day mortality rate was unchanged. For those with persisting RBBB at 60 minutes, 30-day mortality rate was lower if ST-segment elevation had resolved by > or = 50% (20.4% versus 35.3%, P = 0.006). CONCLUSIONS: In patients with anterior AMI and RBBB, increasing QRS duration is associated with increasing 30-day mortality. Early ST-segment resolution after fibrinolytic therapy despite persisting RBBB is associated with lower mortality rate.

Aged↗

PubMed2006

Initial Q waves accompanying ST-segment elevation at presentation of acute myocardial infarction and 30-day mortality in patients given streptokinase therapy: an analysis from HERO-2.

BACKGROUND: The presence of pathological Q waves in the infarct leads on the surface electrocardiogram in an ST-elevation acute myocardial infarction indicates myocardial necrosis. Clinically it might be difficult to ascertain the onset of acute myocardial infarction. Our aim was to assess whether the presence or absence of Q waves at presentation could be used as an indicator of the duration of acute myocardial infarction and predict mortality. METHODS: 15,222 patients with ST-elevation acute myocardial infarction and normal intraventricular conduction were randomly assigned streptokinase and aspirin plus bivalirudin or unfractionated heparin in the HERO-2 trial; randomisation did not alter 30-day mortality. 10,244 patients (67%) had Q waves in the infarct territory at the time of randomisation, and 4978 (33%) did not. The primary endpoint was 30-day mortality. FINDINGS: There were more deaths at 30 days in patients with initial Q waves than in those without (1044 [10%] vs 344 [7%], p<0.0001). These findings were similar in patients with a first acute myocardial infarction and when stratified by time to randomisation (0-2, >2-4, >4 h) and by acute myocardial infarction location (anterior or inferior). Both the presence of initial Q waves and time to randomisation were positive univariate predictors, but only the presence of initial Q waves independently predicted 30-day mortality on multivariate analysis (adjusted OR 1.44, 95% CI 1.25-1.65 with clinical indices, and 1.31, 1.12-1.54 with clinical plus ST indices included as predictors). INTERPRETATION: The presence of Q waves in the infarct leads at presentation of ST-elevation acute myocardial infarction independently predicts higher 30-day mortality in patients treated with fibrinolytic therapy. Therefore, a more aggressive approach to reperfusion might be warranted in these patients.

Aged↗

PubMed2006

Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction.

CONTEXT: Cardiogenic shock remains the major cause of death for patients hospitalized with acute myocardial infarction (MI). Although survival in patients with cardiogenic shock complicating acute MI has been shown to be significantly higher at 1 year in those receiving early revascularization vs initial medical stabilization, data demonstrating long-term survival are lacking. OBJECTIVE: To determine if early revascularization affects long-term survival of patients with cardiogenic shock complicating acute MI. DESIGN, SETTING, AND PATIENTS: The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial, an international randomized clinical trial enrolling 302 patients from April 1993 through November 1998 with acute myocardial infarction complicated by cardiogenic shock (mean [SD] age at randomization, 66 [11] years); long-term follow-up of vital status, conducted annually until 2005, ranged from 1 to 11 years (median for survivors, 6 years). MAIN OUTCOME MEASURES: All-cause mortality during long-term follow-up. RESULTS: The group difference in survival of 13 absolute percentage points at 1 year favoring those assigned to early revascularization remained stable at 3 and 6 years (13.1% and 13.2%, respectively; hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.97; log-rank P = .03). At 6 years, overall survival rates were 32.8% and 19.6% in the early revascularization and initial medical stabilization groups, respectively. Among the 143 hospital survivors, a group difference in survival also was observed (HR, 0.59; 95% CI, 0.36-0.95; P = .03). The 6-year survival rates for the hospital survivors were 62.4% vs 44.4% for the early revascularization and initial medical stabilization groups, respectively, with annualized death rates of 8.3% vs 14.3% and, for the 1-year survivors, 8.0% vs 10.7%. There was no significant interaction between any subgroup and treatment effect. CONCLUSIONS: In this randomized trial, almost two thirds of hospital survivors with cardiogenic shock who were treated with early revascularization were alive 6 years later. A strategy of early revascularization resulted in a 13.2% absolute and a 67% relative improvement in 6-year survival compared with initial medical stabilization. Early revascularization should be used for patients with acute MI complicated by cardiogenic shock due to left ventricular failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000552.

Aged↗

PubMed2006

International variation in invasive care of the elderly with acute coronary syndromes.

AIMS: To explore variations in invasive care of the elderly with acute coronary syndromes across international practice. METHODS AND RESULTS: Using combined populations from the SYMPHONY and 2nd SYMPHONY trials, we describe 30-day cardiac catheterization in elderly (> or = 75 years; n = 1794) vs. younger patients (< 75 years; n = 14,043) after multivariable adjustment and by region of enrolment. The use of cardiac catheterization and revascularization were not protocol-specified. Elderly patients (median age 78 years) were more often female and more frequently had hypertension, diabetes, prior myocardial infarction, and prior coronary bypass surgery. Overall, they underwent less cardiac catheterization than younger patients [53 vs. 63%; adjusted OR 0.53 (0.46, 0.60)]. The absolute rate of cardiac catheterization in the elderly varied from 77% (vs. 91% in younger patients) in the US cohort to 27% (vs. 41% in younger patients) in the non-US cohort. Revascularization of elderly who underwent cardiac catheterization was also higher in US than non-US cohorts (71.3 vs. 53.6%). There was a significant interaction between the patient age and the use of catheterization across US and non-US regions of enrolment, as well as differences in the predictors of catheterization in the elderly. Despite these findings, after adjustment, 90-day rates of death and death or myocardial infarction (MI) were not significantly different in elderly who underwent catheterization compared with those who did not. CONCLUSION: Although older age is universally predictive of lower use of cardiac catheterization, marked variation in catheterization of the elderly exists across international practice. Demonstrated differences in patterns of use suggest a lack of consensus regarding optimal use of an invasive strategy in the elderly.

Acute Disease↗

PubMed2006

Statin use and sex-specific stroke outcomes in patients with vascular disease.

BACKGROUND AND PURPOSE: Although statins reduce the risk of stroke in patients with coronary heart disease, possible differing effects of statins on stroke outcomes based on sex remain uncertain. We investigated the relationships between statin use and sex-specific stroke incidence, severity, and mortality. METHODS: Data from 3 trials of oral glycoprotein IIb/IIIa inhibitors (first and second Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes [SYMPHONY] and Blockade of the glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion [BRAVO]) were pooled and stroke outcomes compared among 8191 baseline statin users versus 14,752 nonusers. Time-to-event data were modeled with proportional hazards regression. Stroke severity was assessed retrospectively with the Canadian Neurological Scale (CNS) based on records with scoreable neurological examinations. RESULTS: A total of 217 subjects had strokes (0.95%). Statin users had a lower risk of stroke in unadjusted (hazard ratio [HR], 0.69; 95% CI, 0.51 to 0.92) and risk-adjusted models (HR, 0.72; 95% CI, 0.53 to 0.97). There was no difference in stroke mortality with statin use (P=0.8). CNS scores could be assigned to 106 of the subjects, with no difference in severity among statin users and nonusers (median CNS=10.5 in users versus CNS=9.75 in nonusers; P=0.14). Women had more severe strokes than men (median CNS=10.5 in men versus 9.5 in women; Poisson regression P=0.035). Women had more severe strokes after adjustment for statin use (P=0.03) and the combination of statin use, atrial fibrillation, and age (P=0.03). CONCLUSIONS: In patients included in these clinical trials of oral glycoprotein IIb/IIIa inhibitors, statin use is associated with a reduced risk of stroke but not severity or mortality. Women had more severe strokes than men, a difference that was not explained by baseline characteristics or statin use.

Aged↗

PubMed2006

Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction.

BACKGROUND: Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose. METHODS: We randomly assigned 20,506 patients with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. RESULTS: The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the enoxaparin group (17 percent reduction in relative risk, P<0.001). Nonfatal reinfarction occurred in 4.5 percent of the patients receiving unfractionated heparin and 3.0 percent of those receiving enoxaparin (33 percent reduction in relative risk, P<0.001); 7.5 percent of patients given unfractionated heparin died, as did 6.9 percent of those given enoxaparin (P=0.11). The composite of death, nonfatal reinfarction, or urgent revascularization occurred in 14.5 percent of patients given unfractionated heparin and 11.7 percent of those given enoxaparin (P<0.001); major bleeding occurred in 1.4 percent and 2.1 percent, respectively (P<0.001). The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage (a measure of net clinical benefit) occurred in 12.2 percent of patients given unfractionated heparin and 10.1 percent of those given enoxaparin (P<0.001). CONCLUSIONS: In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with enoxaparin throughout the index hospitalization is superior to treatment with unfractionated heparin for 48 hours but is associated with an increase in major bleeding episodes. These findings should be interpreted in the context of net clinical benefit. (ClinicalTrials.gov number, NCT00077792.).

Aged↗

PubMed2006

Frequency of recurrent ST-elevation myocardial infarction after fibrinolytic therapy in a different territory as a manifestation of multiple unstable coronary arterial plaques.

Multiple unstable plaques have been demonstrated by various imaging techniques in culprit and nonculprit arteries in patients with acute coronary syndromes, but the frequency with which clinical manifestations of multiple unstable plaques occur is unclear. To estimate this frequency in patients who present within 6 hours with ST-elevation myocardial infarction, we studied electrocardiograms and cardiac marker levels of 722 patients with suspected reinfarction in the HERO-2 trial of 17,073 patients; this trial compared intravenous bivalirudin with unfractionated heparin before administration of streptokinase. Twenty-six patients (3.6%) developed recurrent ST elevation in a different territory. Of all the patients who developed ST elevation in a different territory, 50% (13 of 26) did so during the 48 hours of randomized antithrombin therapy compared with 29% (140 of 487) of those who developed recurrent ST elevation in the index territory (p = 0.046). Recurrent index territory ST elevation occurred in 392 of 552 patients (71%) with confirmed reinfarction, and ST elevation in a new territory occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all HERO-2 enrollees, respectively). These data suggest that clinical manifestation of multiple unstable plaques of recurrent ST elevation and reinfarction in a territory different from that of the index ST elevation myocardial infarction after intravenous fibrinolytic and antithrombin therapies is rare.

Aged↗

PubMed2006

Elevated creatine kinase-MB with normal creatine kinase predicts worse outcomes in patients with acute coronary syndromes: results from 4 large clinical trials.

BACKGROUND: The degree to which elevated creatine kinase (CK)-MB in the presence of normal CK is predictive of outcome is not well understood despite having been studied for decades. This analysis examined whether normal CK with elevated CK-MB in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) is an independent predictor of worse outcomes. A concomitant goal was to contribute insight to the debate over how patients with NSTE ACS should be managed. METHODS: Data for 25,960 patients from the GUSTO IIb, PARAGON A and B, and PURSUIT trials were analyzed. Of these patients, 6402 were excluded from primary analysis because of missing (unmeasured) biomarkers. Patients with complete laboratory data (n = 19,558) were grouped by CK and CK-MB results. To confirm the primary analysis results, data from patients with missing biomarkers were used in an imputation model. RESULTS: Patients were categorized in 1 of 4 groups: normal CK + normal CK-MB; normal CK + elevated CK-MB; elevated CK + normal CK-MB; or elevated CK + elevated CK-MB. For the primary outcome, 180-day death, or myocardial infarction, Kaplan-Meier estimates were 14.9%, 20.8%, 14.5%, and 18.2%, respectively. Regardless of total CK, elevated CK-MB was associated with a 25% to 49% increased relative risk of worse outcomes. Findings from the analyses were verified by the multivariable model. CONCLUSIONS: CK-MB remains a reliable marker for myocardial necrosis and a strong predictor of worse prognosis. All patients with ACS should have CK-MB measurement to search for cardiac ischemia. Patients with elevated CK-MB should receive aggressive management commensurate with their increased risks.

Acute Disease↗

PubMed2006

The cost of acute myocardial infarction in the new millennium: evidence from a multinational registry.

BACKGROUND: Although geographic variation in the treatment of acute myocardial infarction (AMI) has been recognized, the impact of evidence-based international treatment guidelines on such variation is unclear. We sought to characterize resource use and cost of initial hospitalization for AMI in 9 countries and compare the contribution of length of stay (LOS) and procedure use to cost. METHODS: We applied country-specific cost estimates to data from the international AMI registry associated with the VALIANT trial. The registry includes demographic, medical history, treatment, and discharge information for 5573 patients with AMI admitted to 84 sites in 9 countries from November 1999 to June 2001. Hospitalization cost was estimated by imputed discharge diagnosis-related group code and adjusted for the LOS and procedures. Generalized linear regression was used to adjust cost by country; the contribution of LOS and procedures to cost was assessed by ordinary least squares regression. RESULTS: Unadjusted mean cost for initial AMI hospitalization was 9993 dollars (95% CI 9702 dollars-10,228 dollars). After adjustment for baseline patient-level variation, the lowest average cost was 1605 dollars (Argentina) and the highest was 9196 dollars (United States). Length of stay explained more of the variation in cost (50.7%) than did procedure intensity (31.9%). CONCLUSIONS: International differences in the cost of AMI persist, reflecting variations in procedure use and especially LOS. Relative differences in resource costs and incentives inherent in the provision and financing of health care likely contribute to treatment and cost variation and limit the widespread adoption of international practice guidelines.

Aged↗

PubMed2006

Effects of exercise training on 5 inflammatory markers associated with cardiovascular risk.

BACKGROUND: Cross-sectional studies suggest that regular exercise has anti-inflammatory effects, leading to lower levels of several proatherogenic inflammatory markers. However, this has yet to be confirmed by randomized prospective trials. We performed a randomized controlled trial to assess whether exercise training decreases levels of 5 inflammatory markers linked to future cardiovascular risk: white blood cell count, fibrinogen, C-reactive protein, soluble intercellular adhesion molecule 1, and soluble CD40 ligand. METHODS: One hundred fifty-two healthy female smokers were randomized to either 12 weeks of exercise training or health education as part of a smoking cessation program. Smoking was held steady for the first 6 weeks, and thereafter, smoking cessation was actively attempted. One hundred four participants completed 6 weeks, and 88 completed 12 weeks. Fitness and circulating inflammatory marker levels were measured at baseline, 6 weeks, and 12 weeks. To avoid potential confounding from changes in smoking exposure during the second 6 weeks of the trial, the primary end point was change in inflammatory marker levels from baseline to 6 weeks. Change in inflammatory markers from baseline to 12 weeks was a secondary end point. RESULTS: At baseline, greater physical fitness was associated with lower white blood cell, fibrinogen, and C-reactive protein levels, but these associations were not statistically significant after adjusting for body mass index (P > .1 for all). Fitness improved significantly in the exercise group at both 6 and 12 weeks. However, there were no differences in levels of any inflammatory marker between the exercise and control groups at either 6 weeks (primary end point) or 12 weeks (secondary end point) (P > .05 for all comparisons). CONCLUSION: In female smokers, baseline associations between fitness and inflammatory markers were largely attributable to differences in body fat; regular exercise did not reduce levels of any of the inflammatory markers studied despite a significant improvement in fitness at both 6 and 12 weeks.

Adult↗