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C B Granger

Publications and source records attributed to C B Granger.

At least 37 records · Page 2Linked to original sources
PubMed2001

Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.

BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.

Adult↗
PubMed2001

Prediction of the extent and severity of left ventricular dysfunction in anterior acute myocardial infarction by the admission electrocardiogram.

BACKGROUND: The grade of ischemia, as detected by the relation between the QRS complex and ST segment on the admission electrocardiogram, is associated with larger infarct size and increased mortality rates in acute myocardial infarction. METHODS: We assessed the correlation between left ventricular function and the admission electrocardiogram in 151 patients with first anterior acute myocardial infarction who received thrombolytic therapy and underwent cardiac catheterization at 90 minutes and before hospital discharge. The number of leads with ST elevation, sum of ST elevation, maximal Selvester score, and the presence of severe (grade 3) ischemia were determined in each electrocardiogram. Left ventricular ejection fraction, the number of chords with wall motion abnormalities, and the severity of dysfunction (SD/chord) were determined. RESULTS: At 90 minutes, the 39 ischemia grade 3 patients had lower ejection fraction than the 112 grade 2 patients. Both at 90 minutes and at hospital discharge, the grade 3 group had more chords with wall motion abnormalities and more severe regional dysfunction (SD/chord). However, the number of leads with ST elevation, sum of ST elevation, and maximal Selvester score had no correlation with ejection fraction at 90 minutes and only mild correlation with the extent of dysfunction (number of chords) at 90 minutes. There was no correlation between either the number of leads with ST elevation or the sum of ST elevation and the severity of regional dysfunction. CONCLUSIONS: The number of leads with ST elevation, sum of ST elevation, and maximal Selvester score had only mild correlation with the extent of myocardial dysfunction but not with the severity of dysfunction. Grade 3 ischemia is predictive of more extensive myocardial involvement and greater severity of regional dysfunction.

Aged↗
PubMed2001

Clinical, electrocardiographic, and biochemical data for immediate risk stratification in acute coronary syndromes.

The recent evolution in therapeutic options for acute coronary syndromes (ACS) mandates early risk stratification in order to select the appropriate treatment strategy for individual patients. Simple clinical data derived from the patient's medical history and physical examination, a standard twelve-lead electrocardiogram (ECG), and determinations of biochemical markers of myocardial damage can be obtained in the emergency room and serve as a guide for deciding appropriate medical management and optimal use of available resources. Even the most important classification of the ACS is based upon a simple and dichotomous description of the ECG, where the presence of ST-segment elevation mandates an immediate attempt to restore coronary perfusion (either pharmacologically or mechanically), whereas its absence suggests pharmacological stabilization before further evaluation. Across the whole spectrum of ACS, clinical history data (such as older age, previous coronary events, and diabetes) and clinical variables (such as higher heart rate, lower blood pressure, and higher Killip class) are the most powerful prognostic determinants at multivariate analyses derived from large databases. The ECG adds significant and independent prognostic information using the analysis of qualitative (direction of ST-segment shift, associated T-wave inversion, and presence of conduction disturbances) and quantitative (number of leads involved, amount of ST- segment shifts, duration of QRS) characteristics. Biochemical markers of myocardial damage have also been identified as independent predictors of events. In addition, retrospective analyses of clinical trials have suggested that biochemical markers might serve as a guide to select pharmacological therapy. However, how to best combine electrocardiographic and biochemical data for immediate risk stratification remains to be further elucidated.

Aged↗
PubMed2001

Platelet function and fibrinolytic agents: two sides of a coin?

Fibrinolytic therapy is the established treatment for the management of patients with ST elevation acute myocardial infarction (AMI). Present fibrinolytic regimens have a number of shortcomings, including the failure to produce early and sustained reperfusion, as well as failure to prevent reocclusion in at least some patients. Platelets play an important role in coronary thrombosis responsible for AMI. The effect of coronary fibrinolysis on platelets has been extensively debated in the literature with evidence of both platelet activation and inhibition. Among fibrinolytic agents, tissue plasminogen activator (t-PA) is considered to be the mainstay in the treatment of coronary artery disease. The native t-PA molecule has been modified in an attempt to achieve improved lytic characteristics with less risk of bleeding. The result is a group of mutant t-PA variants considered third-generation plasminogen activators. TNK-t-PA is one bioengineered variant of t-PA. Another third-generation plasminogen activator is reteplase (r-PA). Like TNK-t-PA, it is a variant of t-PA that has been developed to establish a more rapid, complete, and stable coronary artery patency, thus promising reduced mortality. Both r-PA and TNK-t-PA are effective when given as bolus therapy. This feature may facilitate more rapid treatment as well as decrease overall costs of treatment. New fibrinolytic regimens include potent antiplatelet agents that may improve sustained reperfusion. This review summarizes the latest and often confusing data on the interaction between fibrinolytic therapy and platelets in certain in vitro, animal and clinical scenarios.

Animals↗
PubMed2000

Strategies of patient care in acute coronary syndromes: rationale for the Global Registry of Acute Coronary Events (GRACE) registry.

An abundance of evidence is available from large, randomized clinical trials supporting the efficacy of therapies for the management of patients with acute coronary syndromes. For ST-segment elevation myocardial infarction (MI), a variety of databases can be used to assess how these therapies, both pharmacologic and invasive, are being integrated into real practice. Little information is available, however, with regard to how newer treatments are actually being implemented for patients with unstable angina and non-ST-segment elevation MI. There are several important issues to consider in evaluating current treatment practices for acute coronary syndromes, including limitations of clinical trial databases, a trend toward progressive shortening of length of hospital stay, and variations in the availability of resources among treatment centers. In response to the need for a broader database that would address the global impact of clinical management practices in acute coronary syndromes, the Global Registry of Acute Coronary Events (GRACE) Registry has been established. The GRACE Registry will initially collect data on patient care from a variety of treatment centers in 14 countries, the plan being to eventually enroll 10,000 patients per year. This international observational database will obtain information on the complete spectrum of acute coronary syndromes, with the specific goals of describing diagnostic and treatment strategies, determining hospital outcomes, improving quality of care, and developing hypotheses for future clinical research.

Angina, Unstable↗
PubMed2000

Clinical and electrocardiographic variables associated with increased risk of ventricular septal defect in acute anterior myocardial infarction.

It is unknown whether the risk factors associated with the development of ventricular septal defect (VSD) after acute myocardial infarction (MI) remain the same when thrombolytic therapy is used, nor have specific electrocardiographic patterns of acute MI associated with the development of VSD been identified. Our study population included patients with an anterior MI enrolled in the GUSTO-I study. Baseline clinical data were collected prospectively for all patients. Patients in whom VSD was suspected by the local investigators at each site were evaluated retrospectively. Baseline clinical and electrocardiographic variables were compared between 2 groups: 10,847 patients without VSD (99.6%) and 48 patients with confirmed VSD (0.4%). Multivariate analysis showed the following clinical variables to be independent predictors of VSD: age (odds ratio [OR] 2.19, 95% confidence intervals [CI] 1.62 to 2.98; p <0.001), female gender (OR 5.07, 95% CI 2.70 to 9.98; p <0.001), and lack of previous angina (OR 2.11, 95% CI 1.12 to 4.29; p = 0.021). Two electrocardiographic variables predicted acute VSD: the magnitude of ST deviation in lead III (OR 1.55, 95% CI 1.12 to 2.21; p = 0.007) and in lead V(2) (p <0.001). However, the relation between the ST amplitude in lead V(2) and the risk for VSD was nonlinear. In patients with anterior MI who underwent thrombolysis, the risk factors for VSD were age, female gender, and lack of previous angina. Previous infarction was not a risk factor. Less ST-segment depression in lead III was a predictor of VSD.

Aged↗
PubMed2000

Canadian-American differences in the management of acute coronary syndromes in the GUSTO IIb trial: one-year follow-up of patients without ST-segment elevation. Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) II Investigators.

BACKGROUND: Little information exists concerning practice patterns between Canada and the United States in the management of myocardial infarction (MI) patients without ST-segment elevation and unstable angina. METHODS AND RESULTS: We examined the practice patterns and 1-year outcomes of 2250 US and 922 Canadian patients without ST-elevation acute coronary syndromes in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial. The US hospitals more commonly had on-site facilities for angiography and revascularization. These procedures were performed more often and sooner in the United States than Canada, whereas Canadian patients were more likely to undergo noninvasive stress testing. The length of initial hospital stay was 1 day longer for Canadian than US patients. Recurrent and refractory ischemia was more common in Canada. One-year mortality was comparable between the 2 countries. However, at 6 months, even after baseline differences were accounted for, the (re)MI rate was significantly higher in Canadian than US patients with unstable angina (8.8% versus 5.8%, P:=0.039), as was the composite rate of death or (re)MI (13.1% versus 9.1%, P:=0.016). CONCLUSIONS: One-year mortality was comparable between Canada and the United States in both MI and unstable angina cohorts despite higher intervention rates in the United States. However, outcomes at 6 months among patients with unstable angina differed. Whereas more frequent coronary interventions were not associated with reduced recurrent MI or death among MI patients without ST elevation, they may favorably affect outcomes in patients with unstable angina.

Analysis of Variance↗
PubMed2000

Use of resources, quality of life, and clinical outcomes in patients with and without new Q waves after thrombolytic therapy for acute myocardial infarction (from the GUSTO-I trial).

Previous reports indicate that patients who do not develop Q waves after thrombolytic therapy are a different population with a better long-term survival than those who do develop Q waves. However, the use of resources, quality of life, and health status of this population have not been fully evaluated. Using data from the Economics and Quality of Life subset of the Global Utilization of Streptokinase and tPA for Occluded Arteries study, we examined 30-day and 1-year mortality, use of resources, and quality-of-life measures among 1,830 of 3,000 patients with acute myocardial infarction and ST-segment elevation treated with thrombolytic therapy. At hospital discharge, 555 patients (30.2%) had not developed Q waves. These patients had lower mortality than patients with Q waves at 30 days (1.6% vs 4.5%, p <0.01) and at 1 year (4.7% vs 6.8%, p <0.04). Recurrent chest pain and dyspnea were similar at 30 days and 1 year. Patients without Q waves had significantly more angiography and trends toward higher readmission, revascularization, and use of calcium antagonists at 30 days. Angiography, revascularization, readmission, and quality of life were equivalent from 30 days to 1 year, with no sign of late instability. Logistic regression analysis showed an association between in-hospital revascularization and better survival and quality of life at 1 year. Conversely, there was no association between in-hospital use of calcium antagonists and outcome to explain the lower mortality in non-Q-wave patients. The absence of Q waves after thrombolytic therapy is a marker of success, implying better prognosis and equivalent quality of life, use of resources, and health status than for patients with Q-wave acute myocardial infarction and no sign of long-term unstable clinical course.

Aged↗
PubMed2000

A comparison of ionic versus nonionic contrast medium during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction (GUSTO IIb). Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes.

The clinical impact of contrast medium selection during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction (AMI) has not been studied. We compared the clinical outcomes of patients who received ionic versus nonionic low osmolar contrast medium in the setting of primary percutaneous transluminal coronary angioplasty for AMI in the second Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) trial. Univariable and multivariable analyses were performed to assess the relation between contrast medium selection and clinical outcome (death, reinfarction, or refractory ischemia) at 30 days. Although baseline clinical and angiographic characteristics were generally similar between the 2 groups, patients who received ionic, low osmolar contrast were less likely to have been enrolled at a US site (23% vs 43%, p = 0.001) and less likely to have occlusion of the left anterior descending coronary artery (34% vs 47%, p = 0.03) or a history of prior AMI (8% vs 16%, p = 0.02). The triple composite end point of death, reinfarction, or refractory ischemia occurred less frequently in the ionic group, both in the hospital (4.4% vs 11%, p = 0.018) and at 30 days (5.5% vs 11%, p = 0.044). Although the trend favoring ionic contrast persisted, the differences were no longer statistically significant after adjustment for imbalances in baseline characteristics using a risk model developed from the study sample (n = 454, adjusted odds ratio for ionic contrast 0.48 [0.22 to 1.02], p = 0.055), and using a model developed from the entire GUSTO IIb study cohort (n = 12,142, adjusted odds ratio for ionic contrast 0.50 [0.23 to 1.06], p = 0.072). The results of this observational study warrant further elucidation by a randomized study design in this setting.

Angioplasty, Balloon, Coronary↗
PubMed2000

Prognostic implications of TIMI flow grade in the infarct related artery compared with continuous 12-lead ST-segment resolution analysis. Reexamining the "gold standard" for myocardial reperfusion assessment.

OBJECTIVE: To compare the prognostic significance of reperfusion assessment by Thrombolysis in Myocardial Infarction (TIMI) flow grade in the infarct related artery and ST-segment resolution analysis, by correlating with clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND: Angiographic assessment, based on epicardial coronary anatomy, has been considered the "gold standard" for reperfusion. The electrocardiogram (ECG) monitoring provides a noninvasive, real-time physiologic marker of cellular reperfusion and may better predict clinical outcomes. METHODS: Two hundred fifty-eight AMI patients from the Thrombolytics and Myocardia Infarction phase 7 and Global Utilization of Streptokinase tPA for Occluded coronary arteries phase 1 trials were stratified based on blinded, simultaneous reperfusion assessment on the acute angiogram (divided into TIMI grades 0 & 1, TIMI grade 2 and TIMI grade 3) and ST-segment resolution analysis (divided into: <50% ST-segment elevation resolution or reelevation and > or =50% ST-segment elevation resolution). In-hospital mortality, congestive heart failure (CHF) and combined mortality or CHF were compared to determine the prognostic significance of reperfusion assessment by each modality using chi-square and Fisher's Exact tests for univariable correlation and logistic regression analysis for univariable and multivariable prediction models. RESULTS: By logistic regression analysis, ST-segment resolution patterns were an independent predictor of the combined outcome of mortality or CHF (p = 0.024), whereas TIMI flow grade was not (p = 0.693). Among the patients determined to have failed reperfusion by TIMI flow grade assessment (TIMI flow grade 0 & 1), the ST-segment resolution of > or =50% identified a subgroup with relatively benign outcomes with the incidence of the combined end point of mortality or CHF 17.2% versus 37.2% in those without ST-segment resolution (p = 0.06). CONCLUSION: Continuous 12-lead ECG monitoring can be an inexpensive and reliable modality for monitoring nutritive reperfusion status and to obtain prognostic information in patients with AMI.

Adult↗
PubMed2000

Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.

BACKGROUND: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. METHODS: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). RESULTS: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). CONCLUSIONS: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.

Aged↗
PubMed2000

Predictors of death and reinfarction at 30 days after primary angioplasty: the GUSTO IIb and RAPPORT trials.

BACKGROUND: Thirty-day death among recipients of fibrinolytic therapy for acute myocardial infarction (MI) is tightly correlated with easily obtainable key demographic and clinical parameters such as age, blood pressure, heart rate, and infarct location. Similar data for primary angioplasty are not available. METHODS AND RESULTS: Data from 2 large, contemporary, primary angioplasty trials were formally combined and analyzed with respect to death and death/repeat MI at 30 days through the use of multivariate logistic regression models. The 1048 patients had a median age of 62 years, and 26% were women. Thirty-eight percent had an anterior infarction. The patients underwent angioplasty at a median delay from symptom onset of 3.8 hours. Death was independently predicted by increasing age (adjusted odds ratio [OR] per decade 2.32, 95% confidence interval [CI] 1.60 to 3.42), whereas a history of smoking (OR 0.29, CI 0.13 to 0.64), Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after angioplasty (OR vs TIMI <3 0.21, CI 0.10 to 0.45) and higher systolic blood pressure (OR per 10 mm Hg 0.73, CI 0.62 to 0. 87) were associated with lower mortality rates. Death or repeat MI was independently associated with increasing age (OR per decade 1.40, CI 1.13 to 1.76) and anterior location of the index MI (OR 1.89, CI 1.12 to 3.20). TIMI grade 3 flow (OR vs TIMI <3 0.40, CI 0.23 to 0. 68) and higher systolic blood pressure (OR per 10 mm Hg 0.79, CI 0. 71 to 0.89) were associated with a lower incidence of death/repeat MI. Time to angioplasty, heart rate, extent of coronary artery disease, participation in 1 of the 2 trials, and all common coronary risk factors did not significantly predict outcome. CONCLUSIONS: Death and reinfarction after primary angioplasty are predominantly predicted by age, hemodynamic instability, and the attainment of TIMI 3 flow in the infarct artery.

Age Distribution↗
PubMed2000

Diabetes mellitus and outcome after primary coronary angioplasty for acute myocardial infarction: lessons from the GUSTO-IIb Angioplasty Substudy. Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes.

OBJECTIVES: We sought to compare the efficacy of primary angioplasty in diabetics versus nondiabetics and to evaluate the relative benefits of angioplasty over thrombolytic therapy among diabetics. BACKGROUND: Primary angioplasty for myocardial infarction is at least as effective as thrombolytic therapy in the general population. However, the influence of diabetic status on outcome after primary angioplasty versus thrombolysis remains unknown. METHODS: Patients in the Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) Angioplasty Substudy were randomized to receive either primary angioplasty or accelerated alteplase. The interaction of diabetic status (diabetics n = 177, nondiabetics n = 961) and treatment strategy with the occurrence of the primary end point (death, nonfatal reinfarction or nonfatal, disabling stroke at 30 days) was analyzed (power to detect a 40% relative reduction in the primary end point with alpha = 0.05 and beta = 0.20). Among patients who were randomized to and underwent primary angioplasty, procedural success (defined as residual stenosis <50% and TIMI grade 3 flow) was assessed based on diabetic status. RESULTS: Compared with nondiabetics, diabetics had worse baseline clinical and angiographic profiles. Despite more severe stenosis and poorer flow in the culprit artery, procedural success with angioplasty was similar for diabetics (n = 81; 70.4%) and nondiabetics (n = 391; 72.4%). Outcome at 30 days was better for nondiabetics randomized to angioplasty versus alteplase (adjusted odds ratio, 0.62; 95% confidence interval, 0.41-0.96) with a similar trend for diabetics (0.70, [0.29-1.72]). We noted no interaction between diabetic status and treatment strategy on outcome (p = 0.88). CONCLUSIONS: Primary angioplasty was similarly successful in diabetics and nondiabetics and appeared to be more effective than thrombolytic therapy among diabetics with acute infarction.

Aged↗
PubMed2000

Influence of diabetes mellitus on clinical outcomes across the spectrum of acute coronary syndromes. Findings from the GUSTO-IIb study. GUSTO IIb Investigators.

AIMS: We examined the characteristics, outcomes, and effects of hirudin vs heparin treatment of diabetic patients across the spectrum of acute coronary syndromes. METHODS AND RESULTS: We studied the 12,142 patients enrolled in the randomized GUSTO-IIb study. Diabetic patients (n=2175) were older, more often female, more often had prior cardiovascular disease, hypertension, and hyperlipidaemia, and less often were current smokers. Diabetic patients had a higher overall incidence of death or (re)infarction at 30 days (13.1% vs 8.5%, P=0.0001), whether they presented with ST-segment elevation (13.9% vs 9.9%, P=0.0017) or not (12.8% vs 7.8%, P=0.0001), and at 6 months (18.8% vs 11.4%, P=0.0001). Among diabetic patients, hirudin was associated with a tendency toward a lower risk of death or (re)infarction at 30 days (12.2% vs 13.9% with heparin) and 6 months (17.8% vs 20.2%). Diabetic patients had more major bleeding, stroke, heart failure, shock, atrioventricular block, and atrial arrhythmias, but no increased risk for ocular bleeding. CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse 30-day and 6-month outcomes, particularly those without ST-segment elevation. The statistically non-significant trend toward improved outcomes with hirudin was similar among patients with and without diabetes, with a greater point estimate for the absolute difference in patients with diabetes.

Aged↗