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Biomedical subjects

Vic Hasselblad

Publications and source records attributed to Vic Hasselblad.

At least 19 recordsLinked to original sources
PubMed2006

Effect of pexelizumab on mortality in patients with acute myocardial infarction or undergoing coronary artery bypass surgery: a systematic overview.

BACKGROUND: Recent trials evaluating the C5 complement inhibitor, pexelizumab, have shown that modulation of inflammation during ischemia/reperfusion in patients with acute myocardial infarction (MI) or undergoing coronary artery bypass graft (CABG) surgery may improve clinical outcomes. METHODS: We performed a systematic overview of individual patient data from all completed randomized controlled trials of pexelizumab to evaluate the effect on all-cause mortality at 30 and 180 days after treatment. We used a random effects model and included all 5916 patients randomized in 4 clinical trials. Patients received placebo, pexelizumab bolus only or pexelizumab bolus followed by a 24-hour infusion. RESULTS: A significant reduction in mortality at 30 days was observed in patients treated with bolus plus infusion (n = 2476) compared with placebo (n = 2492) (2.9% vs 4.2%; relative risk [RR], 0.70; 95% confidence interval [CI], 0.52-0.95; P = .02), with no interaction according to disease state of CABG or acute MI (P for interaction .33). A trend toward a reduction in mortality was observed in patients who received bolus plus infusion or bolus only (n = 3429) compared with placebo (n = 2476) (3.5% vs 4.2%; RR, 0.85; 95% CI, 0.66-1.0975; P = .215), but not in patients who received bolus only (n = 937) compared with placebo (n = 937) (5.2% vs 5.4%; RR, 0.96; 95% CI, 0.66-1.41; P = .918). The mortality benefit with bolus plus infusion compared with placebo persisted through 180 days (P = .05). CONCLUSIONS: Pexelizumab reduced 30-day mortality in this systematic evaluation. Bolus plus infusion dose is being studied in ongoing trials in acute MI and CABG populations.

Adult↗
PubMed2006

Effect of the novel direct factor Xa inhibitor DX-9065a on thrombin generation and inhibition among patients with stable atherosclerotic coronary artery disease.

INTRODUCTION: Thrombin, a pluripotential effector enzyme with prothrombotic, proinflammatory, and mitogenic properties, plays a pivotal role in the pathobiology and clinical expression of atherothrombotic coronary artery disease. Existing anticoagulant drugs have not been shown to attenuate thrombin generation or activity consistently. We sought to investigate the effect of DX-9065a on thrombin generation and inhibition in patients with stable CAD. DX-9065a is a small-molecule, synthetic, direct inhibitor of factor Xa. MATERIALS AND METHODS: Peripheral venous blood samples were collected serially during and after administration of either placebo or 1 of 4 weight-adjusted regimens of DX-9065a, in 73 patients with stable CAD participating in the XaNADU-1B study. RESULTS AND CONCLUSIONS: At baseline, the median (25th, 75th) prothrombin activation fragment 1.2 (F1.2) level was 2.56 (2.05, 3.20) nmol/L, and the median d-dimer level was 0.26 (0.19, 0.38) microg FEU/L. There were significant relationships between measured plasma DX-9065a concentrations and both F1.2 (4.9% decrease for each doubling of DX-9065a) (P<0.0001) and d-dimer (5.5% decrease for each doubling of DX-9065a) (P=0.001). F1.2 was suppressed (below baseline) at 96 h after administration of DX-9065a. Coronary thrombotic events did not occur during or after study drug administration. DX-9065a, the first in a class of small-molecule, direct, selective and reversible factor Xa inhibitors, reduces thrombin generation and fibrin formation among patients with stable CAD. The effect is concentration-dependent and persists for at least 96 h following drug cessation, without biochemical or clinical evidence of rebound.

Aged↗
PubMed2006

Can one assess whether missing data are missing at random in medical studies?

For handling missing data, newer methods such as those based on multiple imputation are generally more accurate than older ones and entail weaker assumptions. Yet most do assume that data are missing at random (MAR). The issue of assessing whether the MAR assumption holds to begin with has been largely ignored. In fact, no way to directly test MAR is available. We propose an alternate assumption, MAR+, that can be tested. MAR+ always implies MAR, so inability to reject MAR+ bodes well for MAR. In contrast, MAR implies MAR+ not universally, but under certain conditions that are often plausible; thus, rejection of MAR+ can raise suspicions about MAR. Our approach is applicable mainly to studies that are not longitudinal. We present five illustrative medical examples, in most of which it turns out that MAR+ fails. There are limits to the ability of sophisticated statistical methods to correct for missing data. Efforts to try to prevent missing data in the first place should therefore receive more attention in medical studies than they have heretofore attracted. If MAR+ is found to fail for a study whose data have already been gathered, extra caution may need to be exercised in the interpretation of the results.

Biomedical Research↗
PubMed2005

Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial.

CONTEXT: Pulmonary artery catheters (PACs) have been used to guide therapy in multiple settings, but recent studies have raised concerns that PACs may lead to increased mortality in hospitalized patients. OBJECTIVE: To determine whether PAC use is safe and improves clinical outcomes in patients hospitalized with severe symptomatic and recurrent heart failure. DESIGN, SETTING, AND PARTICIPANTS: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) was a randomized controlled trial of 433 patients at 26 sites conducted from January 18, 2000, to November 17, 2003. Patients were assigned to receive therapy guided by clinical assessment and a PAC or clinical assessment alone. The target in both groups was resolution of clinical congestion, with additional PAC targets of a pulmonary capillary wedge pressure of 15 mm Hg and a right atrial pressure of 8 mm Hg. Medications were not specified, but inotrope use was explicitly discouraged. MAIN OUTCOME MEASURES: The primary end point was days alive out of the hospital during the first 6 months, with secondary end points of exercise, quality of life, biochemical, and echocardiographic changes. RESULTS: Severity of illness was reflected by the following values: average left ventricular ejection fraction, 19%; systolic blood pressure, 106 mm Hg; sodium level, 137 mEq/L; urea nitrogen, 35 mg/dL (12.40 mmol/L); and creatinine, 1.5 mg/dL (132.6 micromol/L). Therapy in both groups led to substantial reduction in symptoms, jugular venous pressure, and edema. Use of the PAC did not significantly affect the primary end point of days alive and out of the hospital during the first 6 months (133 days vs 135 days; hazard ratio [HR], 1.00 [95% confidence interval {CI}, 0.82-1.21]; P = .99), mortality (43 patients [10%] vs 38 patients [9%]; odds ratio [OR], 1.26 [95% CI, 0.78-2.03]; P = .35), or the number of days hospitalized (8.7 vs 8.3; HR, 1.04 [95% CI, 0.86-1.27]; P = .67). In-hospital adverse events were more common among patients in the PAC group (47 [21.9%] vs 25 [11.5%]; P = .04). There were no deaths related to PAC use, and no difference for in-hospital plus 30-day mortality (10 [4.7%] vs 11 [5.0%]; OR, 0.97 [95% CI, 0.38-2.22]; P = .97). Exercise and quality of life end points improved in both groups with a trend toward greater improvement with the PAC, which reached significance for the time trade-off at all time points after randomization. CONCLUSIONS: Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitalization. Future trials should test noninvasive assessments with specific treatment strategies that could be used to better tailor therapy for both survival time and survival quality as valued by patients.

Catheterization, Swan-Ganz↗
PubMed2005

Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials.

CONTEXT: Randomized clinical trials (RCTs) evaluating the pulmonary artery catheter (PAC) have been limited by small sample size. Some nonrandomized studies suggest that PAC use is associated with increased morbidity and mortality. OBJECTIVE: To estimate the impact of the PAC device in critically ill patients. DATA SOURCES: MEDLINE (1985-2005), the Cochrane Controlled Trials Registry (1988-2005), the National Institutes of Health ClinicalTrials.gov database, and the US Food and Drug Administration Web site for RCTs in which patients were randomly assigned to PAC or no PAC were searched. Results from the ESCAPE trial of patients with severe heart failure were also included. Search terms included pulmonary artery catheter, right heart catheter, catheter, and Swan-Ganz. STUDY SELECTION: Eligible studies included patients who were undergoing surgery, in the intensive care unit (ICU), admitted with advanced heart failure, or diagnosed with acute respiratory distress syndrome and/or sepsis; and studies that reported death and the number of days hospitalized or the number of days in the ICU as outcome measures. DATA EXTRACTION: Information on eligibility criteria, baseline characteristics, interventions, outcomes, and methodological quality was extracted by 2 reviewers. Disagreements were resolved by consensus. DATA SYNTHESIS: In 13 RCTs, 5051 patients were randomized. Hemodynamic goals and treatment strategies varied among trials. A random-effects model was used to estimate the odds ratios (ORs) for death, number of days hospitalized, and use of inotropes and intravenous vasodilators. The combined OR for mortality was 1.04 (95% confidence interval [CI], 0.90-1.20; P = .59). The difference in the mean number of days hospitalized for PAC minus the mean for no PAC was 0.11 (95% CI, -0.51 to 0.74; P = .73). Use of the PAC was associated with a higher use of inotropes (OR, 1.58; 95% CI, 1.19-2.12; P = .002) and intravenous vasodilators (OR, 2.35; 95% CI, 1.75-3.15; P<.001). CONCLUSIONS: In critically ill patients, use of the PAC neither increased overall mortality or days in hospital nor conferred benefit. Despite almost 20 years of RCTs, a clear strategy leading to improved survival with the PAC has not been devised. The neutrality of the PAC for clinical outcomes may result from the absence of effective evidence-based treatments to use in combination with PAC information across the spectrum of critically ill patients.

Catheterization, Swan-Ganz↗
PubMed2005

Diabetes-related knowledge, atherosclerotic risk factor control, and outcomes in acute coronary syndromes.

Patients who have diabetes mellitus have 2 times the incidence of an acute coronary syndrome (ACS) and 2 times the mortality rate after ACS compared with patients who do not have diabetes. Poor patient understanding of diabetes is believed to impede appropriate self-management, thus accelerating cardiovascular complications. We investigated the relation between patients' diabetes-related knowledge (DRK) and measurements of risk factor control and cardiac outcomes. Two hundred patients who had diabetes mellitus and ACS and were admitted to a university hospital were enrolled over a 9-month period. At enrollment, clinical and demographic data were recorded, and each patient completed a previously validated DRK assessment. Clinical outcomes data were obtained 6 months after enrollment. Years of education and DRK assessment score were moderately correlated (r = 0.496, p <0.0001). Glycosylated hemoglobin, low-density lipoprotein cholesterol, and body mass index showed no correlation with DRK assessment score (r = -0.045, -0.005, and 0.175, respectively), even after multivariable adjustment for differences in age, race, insulin requirement, duration of diabetes, and years of education. Rates of 6-month death (6.2% vs 9.7%) and death or myocardial infarction (15.5% vs 19.4%) were not significantly different between groups of patients stratified by DRK assessment scores (high vs low scoring groups). Thus, among patients who have diabetes and ACS, there is a moderate correlation between years of education and DRK. We found no correlation between DRK and measurements of risk factor control or 6-month clinical outcomes. New strategies must be developed to translate understanding of disease into better risk factor modification among patients who have diabetes and ACS.

Aged↗
PubMed2005

Intradialytic blood volume monitoring in ambulatory hemodialysis patients: a randomized trial.

Complications related to inadequate volume management are common during hemodialysis. This trial tested the hypothesis that availability of an intradialytic blood volume monitoring (IBVM) device improves fluid removal, reducing morbidity. A six-center, randomized trial with 6 mo of intervention comparing IBVM using Crit-Line versus conventional clinical monitoring was conducted. The average rate of non-access-related hospitalizations was compared across treatment groups using Poisson regression. Mortality analysis used the Kaplan Meier method. A total of 227 patients were randomized to Crit-Line, and 216 were randomized to conventional monitoring. Both groups had similar baseline characteristics. During the study, no differences in weight, BP, or number of dialysis-related complications were observed. There were 120 and 81 non-access-related hospitalizations in the Crit-Line and conventional monitoring groups. The adjusted risk ratio for non-access-related and access-related hospitalization was 1.61 (95% confidence interval 1.15 to 2.25; P = 0.01) and 1.52 (95% confidence interval 1.02 to 2.28; P = 0.04) for the Crit-Line monitoring group. Mortality was 8.7% in the Crit-Line monitoring group and 3.3% in the conventional group (P = 0.021). Standardized mortality ratios comparing the Crit-Line and conventional monitoring groups to the prevalent hemodialysis population were 0.77 (NS) and 0.26 (P < 0.001). Hospitalization rates were 1.51 and 1.03 events/yr in the Crit-Line and standard monitoring groups, compared with 2.01 for the prevalent hemodialysis population. IBVM was associated with higher nonvascular and vascular access-related hospitalizations and mortality compared with conventional monitoring. The atypically low hospitalization and mortality rates for the conventional monitoring group suggest that these findings should be generalized to the US hemodialysis population with caution.

Adult↗
PubMed2005

Metaanalysis and review of heart failure disease management randomized controlled clinical trials.

BACKGROUND: The medical community has turned to disease management (DM) to bridge the gap between proven therapies and clinical practice for patients with heart failure (HF). The aim of this study was to assess the effectiveness of DM programs in reducing hospitalization and mortality in patients with HF on the basis of the results of existing trials. METHODS: We compared the published results from 19 randomized controlled clinical trials evaluating HF DM programs. A random effects model was used to combine the hazards ratio for all-cause hospitalization across the studies evaluating specific types of HF DM programs. RESULTS: We identified 19 relevant studies, with 5752 enrolled patients, which assessed the benefits of HF DM programs. The overall effect was a significant decrease in all-cause hospitalization for patients with HF. There was significant heterogeneity in the results (P < .0001). CONCLUSIONS: The results of this analysis indicate that HF DM is an intervention that could significantly decrease hospitalization for patients with HF. However, due to differences in the types of strategies and the variety of health care settings in which they were evaluated, further studies of HF DM programs with multiple participating centers are required.

Aged↗
PubMed2005

Intensity and focus of heart failure disease management after hospital discharge.

BACKGROUND: Although features of heart failure disease management programs are broadly outlined, little is known about which interventions are actually used in the outpatient setting or which patients are most likely to require interventions. METHODS AND RESULTS: Between September 2001 and June 2002, we enrolled 32 patients admitted to the Brigham and Women's Hospital Heart Failure Services, Boston, Mass, with decompensated heart failure. The intensity of care and outcomes of these patients were prospectively tracked for more than 90 days. During this time, there were 325 patient contacts (median 8.5 per patient), including 247 calls (median 7 per patient) and 78 clinic visits (median 2 per patient). Brigham and Women's Hospital clinicians adjusted diuretics a total of 109 times (median 2.5 times per patient). When frequency of diuretic adjustments was used to estimate the intensity of care, higher values of blood urea nitrogen at discharge predicted an increased intensity of care during the 90-day follow-up (relative risk [RR] 1.2, 95% confidence interval [CI] 1.0-1.3, P = .02). When frequency of clinic visits, telephone calls, and diuretic adjustments were used to estimate intensity of care, discharge creatinine (RR 1.03, 95% CI 0.99-1.06, P = .05), discharge blood urea nitrogen (RR 1.13, 95% CI 1.04-1.23, P = .004), and length of stay (RR 1.07, 95% CI 1.00-1.13, P = .04) were predictors of the composite end point. CONCLUSIONS: Even after undergoing optimization of medications during admission for acute heart failure, patients in a comprehensive disease management program required frequent interventions to maintain clinical stability. Renal dysfunction was the strongest predictor of increased interventions and worse outcome.

Adrenergic beta-Antagonists↗
PubMed2005

A perspective on trials comparing enoxaparin and unfractionated heparin in the treatment of non-ST-elevation acute coronary syndromes.

BACKGROUND: Non-ST-elevation (NSTE) acute coronary syndrome (ACS) is a serious, acute illness characterized by a high rate of death and morbid events, and antithrombin therapy is integral to its management. Contemporary guidelines from the American College of Cardiology/American Heart Association call for use of low-molecular-weight heparin or unfractionated heparin (UFH). METHODS: A systematic overview of six randomized, controlled trials comparing enoxaparin to UFH in the treatment of NSTE ACS was performed using a random-effects empirical Bayes model. Efficacy end points included the incidence of death or the composite of death and myocardial infarction (MI) at 30 days. Safety end points included major bleeding and transfusion at 7 days. RESULTS: For the aggregate of 21,946 patients, the incidence of the composite of death and MI at 30 days was lower in enoxaparin-treated patients (10.1% vs 11.0% for UFH, OR 0.91, 95% CI 0.83-0.99, number need to treat 107). For the 9,835 patients in these trials who received no prerandomization antithrombin therapy, the composite of death and MI at 30 days occurred in 8.0% and 9.4% of enoxaparin- and UFH-treated patients, respectively (OR 0.81, 95% CI 0.70-0.94, number need to treat 94). There was no significant difference in the incidence of death at 30 days in either population. A nonsignificant trend toward higher rates of major bleeding was seen at 7 days for enoxaparin-treated patients, in both the overall safety population and the population of patients who did not receive antithrombin treatment before randomization, but there was no difference in blood transfusions. CONCLUSION: In a systematic overview of six randomized, controlled trials comparing enoxaparin to UFH in the treatment of NSTE ACS in approximately 22,000 patients, the use of enoxaparin rather than UFH was associated with a modest reduction in the incidence of the composite of death and MI at 30 days without a significant increase in the rate of major bleeding or transfusion at 7 days.

Aged↗
PubMed2005

Demographics, clinical characteristics, and outcomes of patients hospitalized for decompensated heart failure: observations from the IMPACT-HF registry.

BACKGROUND: Hospitalizations for decompensated heart failure are frequent. The Initiation Management Pre-discharge Assessment of Carvedilol Heart Failure (IMPACT-HF) registry collected observational data in patients hospitalized for worsening heart failure to characterize an unselected group of patients and to confirm the generalizability of the IMPACT-HF main trial population. METHODS AND RESULTS: The IMPACT-HF registry was conducted concurrently with the IMPACT-HF study, a randomized trial of in-hospital initiation of carvedilol compared with the standard practice of postdischarge beta-blocker initiation. Patients were eligible for registry enrollment if they were hospitalized for heart failure regardless of ejection fraction. There were no exclusions to participation. Patients were followed for 60 days. The IMPACT-HF Registry enrolled 567 patients. The mean age was 71 years, 52% of the patients were men and 82% were Caucasian. At discharge, 71% received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 41% received digoxin, and 62% received beta-blockers. The 60-day rate of rehospitalization or death was 31%. CONCLUSION: The IMPACT-HF registry enrolled elderly patients admitted for worsening heart failure primarily resulting from progressive volume overload. The 60-day rate of death or rehospitalization was high despite the use of evidence-based therapies. New treatments for this population are needed to decrease the morbidity and mortality associated with decompensated heart failure.

Adrenergic beta-Antagonists↗
PubMed2005

A systematic review of diabetes disease management programs.

OBJECTIVE: To systematically evaluate and synthesize published evidence regarding the effect of disease management programs for patients with diabetes mellitus on processes and outcomes of care. STUDY DESIGN: Systematic literature review and meta-analysis. PATIENTS AND METHODS: Computerized databases were searched for English-language controlled studies assessing the effect of diabetes disease management programs published from 1987 to 2001. Two reviewers extracted study data using a structured abstraction form. Pooled estimates of program effects on glycated hemoglobin were calculated using an empirical Bayes model. RESULTS: The pooled estimate of program effects on glycated hemoglobin was a 0.5-percentage point reduction (95% confidence interval, 0.3 to 0.6 percentage points), a modest but significant improvement. Evidence also supports program benefits in improving screening for retinopathy and foot lesions. CONCLUSIONS: Diabetes disease management programs can improve glycemic control to a modest extent and can increase screening for retinopathy and foot complications. Further efforts will be required to create more effective disease management programs for patients with diabetes mellitus.

Blood Pressure↗
PubMed2004

Does disease management improve clinical and economic outcomes in patients with chronic diseases? A systematic review.

PURPOSE: To assess the clinical and economic effects of disease management in patients with chronic diseases. METHODS: Electronic databases were searched for English-language articles from 1987 to 2001. Articles were included if they used a systematic approach to care and evaluated patients with chronic disease, reported objective measurements of the processes or outcomes of care, and employed acceptable experimental or quasi-experimental study designs as defined by the Cochrane Effective Practice and Organization of Care Group. RESULTS: Two reviewers evaluated 16,917 titles and identified 102 studies that met the inclusion criteria. Identified studies represented 11 chronic conditions: depression, diabetes, rheumatoid arthritis, chronic pain, coronary artery disease, asthma, heart failure, back pain, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia. Disease management programs for patients with depression had the highest percentage of comparisons (48% [41/86]) showing substantial improvements in patient care, whereas programs for patients with chronic obstructive pulmonary disease (9% [2/22]) or chronic pain (8% [1/12]) appeared to be the least effective. Of the outcomes more frequently studied, disease management appeared to improve patient satisfaction (71% [12/17]), patient adherence (47% [17/36]), and disease control (45% [33/74]) most commonly and cost-related outcomes least frequently (11% to 16%). CONCLUSION: Disease management programs were associated with marked improvements in many different processes and outcomes of care. Few studies demonstrated a notable reduction in costs. Further research is needed to understand how disease management can most effectively improve the quality and cost of care for patients with chronic diseases.

Cardiovascular Diseases↗
PubMed2004

Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial.

CONTEXT: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban with unfractionated heparin independently have shown superior efficacy over unfractionated heparin alone in patients with non-ST-elevation acute coronary syndromes (ACS). It is not clear if combining enoxaparin with glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current standard combination of unfractionated heparin with glycoprotein IIb/IIIa inhibitors. OBJECTIVE: To assess efficacy and safety of the combination of enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in patients with non-ST-elevation ACS. DESIGN, SETTING, AND PARTICIPANTS: A prospective, international, open-label, randomized, noninferiority trial of 1 mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted intravenous unfractionated heparin (n = 1961) in patients with non-ST-elevation ACS receiving tirofiban and aspirin. Phase A of the A to Z trial was conducted between December 1999 and May 2002. MAIN OUTCOME MEASURES: Death, recurrent myocardial infarction, or refractory ischemia at 7 days in the intent-to-treat population with boundaries set for superiority and noninferiority. Safety based on measures of bleeding using the Thrombolysis in Myocardial Infarction (TIMI) classification system. RESULTS: A total of 169 (8.4%) of 2018 patients randomized to enoxaparin experienced death, myocardial infarction, or refractory ischemia at 7 days compared with 184 (9.4%) of 1952 patients randomized to unfractionated heparin (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.71-1.08). This met the prespecified criterion for noninferiority. All components of the composite primary and secondary end points favored enoxaparin except death, which occurred in only 1% of patients (23 for enoxaparin and 17 for unfractionated heparin). Rates for any TIMI grade bleeding were low (3.0% for enoxaparin and 2.2% for unfractionated heparin; P =.13). Using a worst-case approach that combined 2 independent bleeding evaluations, use of enoxaparin was associated with 1 additional TIMI major bleeding episode for each 200 patients treated. CONCLUSIONS: In patients receiving tirofiban and aspirin, enoxaparin is a suitable alternative to unfractionated heparin for treatment of non-ST-elevation ACS. The 12% relative and 1% absolute reductions in the primary end point in favor of enoxaparin met criterion for noninferiority and are consistent with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.

Aged↗
PubMed2004

Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview.

CONTEXT: Antithrombin therapy has become a guidelines-recommended standard of care in the treatment of acute coronary syndromes (ACS), but recent trials comparing use of enoxaparin and unfractionated heparin in ACS have yielded less robust efficacy and safety results than have earlier trials of these antithrombin therapies. OBJECTIVE: To systematically evaluate the end points of all-cause death and nonfatal myocardial infarction (MI), transfusion, and major bleeding observed in the 6 randomized controlled trials comparing enoxaparin and unfractionated heparin in treatment of ACS. DATA SOURCES: The primary data sets for ESSENCE, A to Z, and SYNERGY were available at the Duke Clinical Research Institute. Baseline characteristics and event frequencies for TIMI 11B, ACUTE II, and INTERACT were provided by the principal investigator of each study. STUDY SELECTION: All 6 randomized controlled trials comparing enoxaparin and unfractionated heparin in non-ST-segment elevation ACS were selected for analysis. DATA EXTRACTION: Efficacy and safety end points were extracted from the overall trial populations and the subpopulation receiving no antithrombin therapy prior to randomization. DATA SYNTHESIS: Systematic evaluation of the outcomes for 21 946 patients was performed using a random-effects empirical Bayes model. No significant difference was found in death at 30 days for enoxaparin vs unfractionated heparin (3.0% vs 3.0%; odds ratio [OR], 1.00; 95% confidence interval [CI], 0.85-1.17). A statistically significant reduction in the combined end point of death or nonfatal MI at 30 days was observed for enoxaparin vs unfractionated heparin in the overall trial populations (10.1% vs 11.0%; OR, 0.91; 95% CI, 0.83-0.99; number needed to treat, 107). A statistically significant reduction in the combined end point of death or MI at 30 days was also observed for enoxaparin in the populations receiving no prerandomization antithrombin therapy (8.0% vs 9.4%; OR, 0.81; 95% CI, 0.70-0.94; number needed to treat, 72). No significant difference was found in blood transfusion (OR, 1.01; 95% CI, 0.89-1.14) or major bleeding (OR, 1.04; 95% CI, 0.83-1.30) at 7 days after randomization in the overall safety population or in the population of patients receiving no prerandomization antithrombin therapy. CONCLUSION: In a systematic overview of approximately 22 000 patients across the spectrum of ACS, enoxaparin is more effective than unfractionated heparin in preventing the combined end point of death or MI.

Angina Pectoris↗
PubMed2004

Usefulness of an elevated troponin-I in predicting clinical events in patients admitted with acute heart failure and acute coronary syndrome (from the RITZ-4 trial).

The relation of cardiac troponin-I (cTnI) to clinical outcomes was examined in patients with decompensated heart failure and concomitant acute coronary syndrome enrolled into the Randomized Intravenous TeZosentan 4 (RITZ-4) study. RITZ-4 was a multicenter, randomized, double-blind, placebo-controlled trial of the endothelin receptor antagonist tezosentan in patients admitted with acute heart failure and concomitant acute coronary syndrome. One hundred ninety-two patients were enrolled in this study. Patients with baseline cTnI values were included in this analysis, and the relation between cTnI and the composite clinical primary end point of RITZ-4 was evaluated.

Acute Disease↗
PubMed2004

Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial.

OBJECTIVES: The Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial was an investigator-initiated study to evaluate if predischarge carvedilol initiation in stabilized patients hospitalized for heart failure (HF) increased the number of patients treated with beta-blockade at 60 days after randomization without increasing side effects or length of hospital stay. BACKGROUND: Beta-blockers are underused in HF. Predischarge initiation may improve the use of evidence-based beta-blockade. METHODS: The IMPACT-HF was a prospective, randomized open-label trial conducted in 363 patients hospitalized for HF. Patients were randomized to carvedilol initiation pre-hospital discharge or to postdischarge initiation (>2 weeks) of beta-blockade at the physicians' discretion. The primary end point of the study was the number of patients treated with beta-blockade at 60 days after randomization. Secondary end points included the number of patients discontinuing beta-blockade, median dose achieved, and a composite of death, rehospitalization, unscheduled visit for HF, or > or =50% increase in oral diuretic, new oral diuretic, or any intravenous therapy with diuretics, inotropes, or other vasoactive agents. RESULTS: At 60 days 165 patients (91.2%) randomized to predischarge carvedilol initiation were treated with a beta-blocker, compared with 130 patients (73.4%) randomized to initiation postdischarge (p < 0.0001). Predischarge initiation was not associated with an increased risk of serious adverse events. The median length of stay was five days in both groups. CONCLUSIONS: Predischarge initiation of carvedilol in stabilized patients hospitalized for HF improved the use of beta-blockade at 60 days without increasing side effects or length of stay. Predischarge initiation may be one approach to improve beta-blocker use in this population.

Adrenergic beta-Antagonists↗