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Biomedical subjects

Paul W Armstrong

Publications and source records attributed to Paul W Armstrong.

At least 19 recordsLinked to original sources
PubMed2003

Effect of pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to fibrinolysis in acute myocardial infarction: the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) trial.

BACKGROUND: Complement activation mediates myocardial damage that occurs during ischemia and reperfusion through multiple pathways. We performed 2 separate, parallel, double-blind, placebo-controlled trials to determine the effects of pexelizumab (a novel C5 complement monoclonal antibody fragment) on infarct size in patients receiving reperfusion therapy: COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) and COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA). The COMPLY trial is reported here. METHODS AND RESULTS: Overall, 943 patients with acute ST-segment elevation myocardial infarction (MI) (20% with isolated inferior MI) receiving fibrinolysis were randomly assigned <6 hours after symptom onset to placebo, pexelizumab 2.0-mg/kg bolus, or pexelizumab 2.0-mg/kg bolus plus 0.05 mg/kg per h for 20 hours. Infarct size determined by creatine kinase-MB area under the curve was the primary analysis, which included patients who received at least some study drug and fibrinolysis (n=920). The median infarct size did not differ by treatment (placebo, 5230; bolus, 4952; bolus plus infusion, 5557 [ng/mL] x h; bolus versus placebo, P=0.85; bolus plus infusion versus placebo, P=0.81), nor did the 90-day composite incidence of death, new or worsening congestive heart failure, shock, or stroke (placebo, 18.6%; bolus, 18.4%; bolus plus infusion, 19.7%). Pexelizumab inhibited complement for 4 hours with bolus-only dosing and for 20 to 24 hours with bolus-plus-infusion dosing, with no increase in infections. CONCLUSIONS: When used adjunctively with fibrinolysis, pexelizumab blocked complement activity but reduced neither infarct size by creatine kinase-MB assessment nor adverse clinical outcomes.

Aged↗
PubMed2003

Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial.

BACKGROUND: Complement, activated during myocardial ischemia and reperfusion, causes myocardial damage through multiple processes. The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial was performed to determine the effect of pexelizumab, a C5 complement inhibitor, on infarct size in patients with ST-segment-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: In COMMA, 960 patients with MI (20% isolated inferior MI) were randomized to placebo, pexelizumab 2.0-mg/kg bolus, or pexelizumab 2.0-mg/kg bolus and 0.05-mg/kg per h infusion for 20 hours. Infarct size by creatine kinase-MB area under the curve, the primary outcome, did not differ significantly between groups (placebo median, 4393; bolus pexelizumab, 4526; bolus plus infusion pexelizumab, 4713 [ng/mL] x h; P=0.89 for bolus versus placebo; P=0.76 for bolus plus infusion versus placebo), nor did the composite of 90-day death, new or worsening heart failure, shock, or stroke (placebo, 11.1%; bolus, 10.7%; bolus plus infusion, 8.5%). The ninety-day mortality rate was significantly lower with pexelizumab bolus plus infusion (1.8% versus 5.9% with placebo; nominal P=0.014); the bolus-only group had an intermediate mortality rate (4.2%). CONCLUSIONS: In patients with ST-elevation MI undergoing percutaneous coronary intervention, pexelizumab had no measurable effect on infarct size. However, the significant reduction in mortality suggests that pexelizumab may benefit patients through alternative novel mechanisms and provides impetus for additional investigation.

Aged↗
PubMed2003

Prognostic value of isolated troponin elevation across the spectrum of chest pain syndromes.

The risk of death or recurrent myocardial infarction (MI) in patients with chest pain and baseline isolated troponin elevation is unclear. To determine the early and short-term risk of death or MI associated with isolated troponin elevation across a spectrum of chest pain syndromes, we used baseline creatine kinase (CK)-MB and troponin data from the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) B troponin substudy, the Global Utilization of Strategies To Open Occluded Coronary Arteries (GUSTO) IIa troponin substudy, and the Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) study. Patients were grouped into 1 of 4 categories based on marker status (troponin-positive/CK-MB-positive, troponin-positive/CK-MB-negative, troponin-negative/CK-MB-positive, or troponin-negative/CK-MB-negative). The adjusted odds of death or MI occurring at 24 hours and 30 days was assessed by baseline marker status using multivariable logistic regression, with the group negative for both markers used as the reference. Patients who were positive for both markers had the highest odds of the 24-hour and 30-day end point. The adjusted odds of the 30-day end point for patients with isolated troponin elevation were 1.3 (95% confidence interval 0.7 to 2.3) and 4.8 (95% confidence interval 1.4 to 16.0) for high- and low-risk patients, respectively. The risk for 24-hour and 30-day death or MI with isolated positive CK-MB results was lower than with isolated positive troponin results, and it was not significantly greater than if the 2 markers were negative. For patients with high- and low-risk chest pain, baseline troponin elevation without CK-MB elevation was associated with increased risk for early and short-term adverse outcomes. This suggests that these patients should be admitted to the hospital and monitored in either an intensive care or step-down unit.

Aged↗
PubMed2003

Implantable cardioverter defibrillators in primary and secondary prevention: a systematic review of randomized, controlled trials.

BACKGROUND: Sudden cardiac death is common in persons with cardiovascular disease. PURPOSE: To assess the efficacy of implantable cardioverter defibrillators (ICDs) in persons at increased risk for sudden cardiac death. DATA SOURCES: MEDLINE (1980-2002), EMBASE (1980-2002), Cochrane Controlled Clinical Trial Registry (2002, Volume 3), other databases, and conference proceedings. Primary study authors and device manufacturers were contacted, and bibliographies of relevant papers were hand searched. STUDY SELECTION: Randomized, controlled clinical trials evaluating ICDs versus usual care were selected. DATA EXTRACTION: Two reviewers extracted data independently. DATA SYNTHESIS: Eight trials were included in the final analysis (4909 patients, 1154 deaths). Compared with usual care (most commonly amiodarone therapy), ICDs significantly reduced sudden cardiac death (relative risk [RR], 0.43 [95% CI, 0.35 to 0.53]) and all-cause mortality (RR, 0.74 [CI, 0.67 to 0.82]). The included trials were divided a priori into two categories: secondary prevention (involving patients resuscitated after cardiac arrest or unstable ventricular tachycardia or ventricular fibrillation [ n = 1963]) and primary prevention (involving patients at increased risk for sudden cardiac death but without documented cardiac arrest, ventricular fibrillation, or ventricular tachycardia [ n = 2946]). Regardless of baseline risk, ICDs were equally efficacious in preventing sudden cardiac death in both types of trials (RR, 0.50 [CI, 0.38 to 0.66] for secondary prevention vs. 0.37 [CI, 0.27 to 0.50] for primary prevention). However, the magnitude of benefit in total mortality varied within the primary prevention trials depending on baseline risk for sudden cardiac death. CONCLUSIONS: Implantable cardioverter defibrillators prevent sudden cardiac death regardless of baseline risk. However, their impact on total mortality is sensitive to baseline risk for arrhythmic death. Decisions about resource allocation for ICDs depend on accurate stratification of patients according to risk.

Arrhythmias, Cardiac↗
PubMed2003

Impact of on-site cardiac interventional facilities on management and outcome of patients with acute coronary syndromes.

OBJECTIVES: To investigate the impact of on-site cardiac interventional facilities on the management and outcome of patients with versus those without ST elevation acute coronary syndromes (ACS) in the Canadian-American Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb population. METHODS: Data from 4605 patients were analyzed in relation to the admitting hospital's capability to perform coronary procedures (noninvasive, angiography-capable and interventional hospitals). Differences in medication use, revascularization rate and patient outcome were determined. RESULTS: Whereas medication use during hospitalization and at discharge differed between non-ST elevation ACS patients treated in the three groups, these were generally more comparable among ST elevation ACS patients. In both ST segment cohorts, patients treated in interventional hospitals underwent coronary procedures more often (angiography rate greater than 70% versus 40% for noninvasive hospitals) and sooner (median two to three days versus four days in noninvasive hospitals) than those treated in other hospitals. Recurrent ischemia was significantly less common in non-ST elevation ACS patients treated in interventional hospitals (32% versus 36% in angiography-capable and 40% in noninvasive hospitals, P<0.001) and tended to be less common among ST elevation ACS patients treated in interventional hospitals. Patients treated in interventional hospitals tended to have lower mortality in the non-ST elevation ACS cohort but significantly fewer died in the ST elevation ACS during hospitalization and at 30 days, six months and one year (8.8% versus 11% in angiography-capable and 15% in noninvasive hospitals, P=0.015). These differences in mortality persisted after adjustment for key baseline covariates. Separate analysis of Canadian and American patients revealed similar mortality patterns, as to the total population, in both ST segment cohorts. CONCLUSIONS: Presence of an on-site cardiac interventional facility favourably affected the management and outcome of ACS patients in both non-ST and ST elevation cohorts.

Acute Disease↗
PubMed2003

Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients.

OBJECTIVES: Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT; and 2) explore whether the time to evaluation impacted on each marker's relative prognostic utility. BACKGROUND: The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively. METHODS: The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST (n = 387), 1 mm ST (n = 433), and ST > or =2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of > or =0.1 ng/ml. RESULTS: Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST and 26.8% among cTnT-positive patients with ST > or =2 mm. On ECGs done after 6 h of symptom onset, ST > or =2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5). CONCLUSIONS: Quantitative ST and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making.

Acetates↗
PubMed2003

Randomized evaluation of the safety and efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide.

BACKGROUND: Current pharmacotherapeutic options for high-risk non-ST-segment elevation acute coronary syndrome patients include aspirin, clopidogrel, heparin, and platelet glycoprotein IIb/IIIa inhibition. A key issue of uncertainty is the safety and efficacy of combination glycoprotein IIb/IIIa inhibitor and low-molecular-weight heparin therapy. METHODS AND RESULTS: We randomized 746 patients with rest ischemic discomfort within 24 hours after the onset of symptoms and ST-segment deviation and/or elevation of serum cardiac markers to receive open-label enoxaparin (1 mg/kg subcutaneously twice daily) or unfractionated heparin (70-U/kg bolus; 15 U x kg(-1) x h(-1) infusion, titrated to an activated partial thromboplastin time of 1.5 to 2 times control) for 48 hours. All patients received aspirin and eptifibatide (180- microg/kg bolus; 2 microg x kg(-1) x min(-1) infusion). Major non-coronary artery bypass surgery-related bleeding at 96 hours (primary safety outcome) was significantly lower among enoxaparin-treated patients than among heparin-treated patients (1.8% versus 4.6%, P=0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, P=0.003). Patients in the enoxaparin group were less likely to experience ischemia as detected by continuous ECG evaluation (primary efficacy outcome) during the initial (14.3% versus 25.4%, P=0.0002) and subsequent (12.7% versus 25.9%, P<0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, P=0.031). CONCLUSIONS: When aspirin and eptifibatide are used in high-risk non-ST-segment elevation acute coronary syndrome patients, enoxaparin improves outcomes (determined on the basis of better safety and efficacy) compared with currently recommended unfractionated heparin therapy and provides a useful novel alternative therapeutic strategy.

Acute Disease↗
PubMed2003

Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure.

BACKGROUND: Although previous work has suggested that anemia is associated with an increased mortality in selected patients with congestive heart failure (CHF), little is known about the prevalence and predictors of anemia, or whether anemia is an independent prognostic factor in unselected, community-based patients with CHF. METHODS AND RESULTS: We analyzed a population-based cohort of patients with new-onset CHF from a database of patients discharged from 138 acute-care hospitals in Alberta, Canada, between April 1993 and March 2001. Logistic regression, Kaplan-Meier survival analyses, and Cox proportional hazards model were used. Among the 12 065 patients with CHF (median age 78 years), 17% had anemia, 58% of whom had anemia of chronic disease. After adjustment for clinical and demographic variables, patients with anemia were more likely to be older (odds ratio [OR] 1.01 per year) and female (OR 1.2 [95% confidence interval 1.1 to 1.3]) and to have a history of chronic renal insufficiency (OR=3.2 [95% confidence interval 2.8 to 3.6]), or hypertension (OR 1.3 [95% confidence interval 1.2 to 1.5]). Hazard ratios for mortality, adjusting for covariates, were 1.34 (1.24 to 1.46) in anemic patients, and 1.36 (1.23 to 1.50) in those patients with anemia of chronic disease. CONCLUSIONS: In this large cohort of community-dwelling patients with CHF, anemia is common and an independent prognostic factor for mortality. Further research into the mechanisms of anemia in CHF and randomized controlled trials to test whether correction of anemia improves prognosis in CHF are needed.

Aged↗
PubMed2003

The impact of gender on the treatment and outcomes of patients with early reinfarction after fibrinolysis: insights from ASSENT-2.

AIMS: To assess gender differences in patients with early reinfarction after fibrinolysis for acute myocardial infarction (AMI) and the impact of these differences on treatment and outcomes. METHODS AND RESULTS: We studied 3.7% of men (n=481) and 4.8% of women (n=189) with early reinfarction after fibrinolysis for AMI in the ASSENT-2 trial of 16,949 patients. Women with reinfarction were older and more often had hypertension, diabetes, and major bleeding prior to reinfarction. Despite adjustment for these differences, women with reinfarction were less likely to receive repeat fibrinolytic therapy (OR: 0.55; 95% CI: 0.37-0.84). Aggressive treatment by either repeat fibrinolysis or urgent revascularization was associated with reduced 1-year mortality irrespective of gender. Death within 24 h of reinfarction was more frequent in women and accounted for a greater proportion of their 1-year mortality (56.0 vs 34.8%; p=0.02). The excess mortality in women at 1 year (27.3 vs 19.9%; p=0.045) was eliminated after adjustment for gender differences in baseline risk profile. CONCLUSION: Women with early reinfarction following fibrinolysis for AMI had more frequent early death and were managed less aggressively. These findings suggest the need for increased awareness and timely intervention in these patients.

Aged↗
PubMed2003

ST segment resolution in ASSENT 3: insights into the role of three different treatment strategies for acute myocardial infarction.

AIMS: ASSENT 3 (Assessment of the Safety and Efficacy of a New Thrombolytic) demonstrated that the bolus fibrinolytic tenecteplase (TNK), combined with enoxaparin (ENOX) or abciximab (ABCX), substantially reduced ischemic complications of acute myocardial infarction as compared with unfractionated heparin (UH). We compared ST resolution in each of the three treatment regimens in order to evaluate the speed, extent and stability of ST segment resolution and its relationship to the primary composite endpoint(s) of the trial. METHODS AND RESULTS: We evaluated ST segment shift and its subsequent resolution i.e. complete (> or =70%), partial (<70-30%) and no resolution (<30%) in 4,304 patients 60 and 180 min after treatment. Sixty minutes after therapy there was a trend for both half-dose TNK/ABCX and TNK/UH to have more frequent complete ST resolution (P=0.072) than TNK/ENOX. Pair-wise comparison at 60 min revealed that patients receiving TNK/ABCX had significantly more complete ST resolution than TNK/ENOX (P=0.026). Further ST resolution had occurred 180 min after treatment: complete ST resolution was greater with TNK/ABCX (59.2%) than the TNK/heparin (50.8%) and TNK/enoxaparin (50.8%) (P<0.001). In the TNK/ENOX group achieving complete ST resolution by 180 min, in-hospital reinfarction was 1.9% vs 4.2% for TNK/UH (P=0.015) representing a 2.3% absolute and 55% relative reduction in reinfarction. Thirty day and one year mortality was greatest amongst those patients with <30% ST segment resolution in the TNK/ABCX group. CONCLUSIONS: More rapid and complete ST resolution occurs with half-dose TNK/ABCX whereas less reinfarction occurs amongst those patients with > or =70% ST resolution receiving either TNK/ABCX or TNK/ENOX. These data highlight two potentially complementary mechanisms of clinical benefit associated with different pharmacologic regimens in acute myocardial infarction, i.e. more rapid versus more stable coronary patency.

Abciximab↗
PubMed2003

Development and validation of a simple model to predict severe coronary artery disease after myocardial infarction: potential impact on cardiac catheterization use in the United States and Canada.

BACKGROUND: Improved patient selection may optimize the efficiency of cardiac catheterization in both high- and low-rate regions. The purpose of this study was to develop and validate a clinical model for predicting high-risk coronary artery disease (CAD) after myocardial infarction (MI) and to examine the model's potential impact on the use rate of both US and Canadian catheterization practices. METHODS AND RESULTS: By the use of baseline clinical variables from 1122 patients in the angiographic substudy of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-1) trial, we developed a model that was predictive of severe CAD (left main or triple-vessel disease). The final model, which included prior MI, age, sex, hyperlipidemia, and decreased left ventricular ejection fraction (C-index = 0.70), was externally validated in 781 patients in the GUSTO IIb trial. Although the probability of severe CAD predicted 5-year survival, the frequency of catheterization in both Canada and the United States bore no relationship to severe CAD risk in the GUSTO-1 trial. By use of the model, we estimated that as much as 15% of US catheterizations from both GUSTO-1 and GUSTO IIb might have been avoided, without significantly compromising the number of patients with severe CAD who were identified (sensitivity = 0.94). By applying the model to Canadian practices, an additional 30 cases of severe CAD might have been identified per every 1000 catheterizations performed, without increasing the catheterization rate. CONCLUSIONS: The likelihood of severe CAD after ST-elevation MI may be predicted from simple baseline clinical variables. The use of a severe CAD predictive model to guide patient selection might enhance the cost-effectiveness of both aggressive and conservative catheterization practices.

Analysis of Variance↗
PubMed2003

Sustained ventricular arrhythmias and mortality among patients with acute myocardial infarction: results from the GUSTO-III trial.

BACKGROUND: In many patients, ventricular arrhythmias will develop early after acute myocardial infarction. We studied the incidence, timing, and outcomes of such arrhythmias in the international Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO)-III trial. METHODS: We identified independent predictors of inhospital ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared 30-day and 1-year mortality rates of patients who did (n = 1121) and did not (n = 13,921) have these arrhythmias during the index hospitalization. RESULTS: Significant independent predictors of inhospital VF were higher Killip class, lower baseline systolic pressure, intravenous preenrollment lidocaine use, shorter time to thrombolysis, and beta-blocker use <2 weeks before enrollment; independent predictors of inhospital VT were lower baseline systolic pressure, intravenous lidocaine use before enrollment, higher Killip class, faster baseline heart rate, and advanced age. The 30-day mortality rate was 31% in patients with VF, 24% in those with VT, 44% in those with both, and 6% in those with neither (P =.001). The corresponding 1-year mortality rates were 34%, 29%, 49%, and 9% (P =.001). The 30-day and 1-year mortality rates were higher for patients with late (>48 hours after enrollment) versus early arrhythmias (< or =48 hours after enrollment). CONCLUSIONS: Despite thrombolysis, inhospital ventricular arrhythmias are associated with higher 30-day and 1-year mortality rates after acute myocardial infarction, particularly when occurring later during the initial hospitalization. Better therapies are needed to improve outcomes of these arrhythmias.

Acute Disease↗
PubMed2003

Prehospital management of acute ST-elevation myocardial infarction: a time for reappraisal in North America.

Although the medical and technologic revolution in the last 3 decades has improved clinical outcome in patients sustaining acute ST-elevation myocardial infarction (STEMI), residual morbidity and mortality remain major health concerns. The critical roles of temporal delay and optimal sustained patency as modulators of successful reperfusion have been repeatedly demonstrated, and investigation into the ideal interface between pharmacologic and mechanical reperfusion continues. Despite physician awareness and patient education programs, time from symptom onset to treatment in STEMI remains stalled at approximately 3 hours for pharmacologic reperfusion, as documented in major clinical trials. Multifaceted improvements with advanced paramedic training, transmittable 12-lead electrocardiograms, and bolus fibrinolytics facilitate potential prehospital diagnosis and treatment. Thus, as we proceed into the 21st century, it is essential to reexamine strategies for addressing these and other issues relating to the process of delivering optimal care to most patients with STEMI. Especially notable are the opportunities provided through prehospital management with initiation of therapy, triage to appropriate hospitals, or both as major potential avenues to further enhance patient outcomes. We review past research in prehospital therapy for STEMI and practical impediments to implementation to establish a framework for interpretation of future developments.

Clinical Trials as Topic↗