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Biomedical subjects

Robert M Califf

Publications and source records attributed to Robert M Califf.

At least 37 records · Page 2Linked to original sources
PubMed2006

Optimizing use of revascularization and clinical outcomes in ST-elevation myocardial infarction: insights from the GUSTO-V trial.

AIMS: To examine the relationship between revascularization within 7 days and 1-year mortality among ST-elevation myocardial infarction patients enrolled in GUSTO-V trial (n=13 451). To examine the relative contribution of system and patient level factors to the variation in international revascularization rates, and their impact on mortality outcomes. METHODS AND RESULTS: Patients from North America (USA, Canada), Australia, and Europe (UK, France, Germany, Italy, Spain, Poland, Norway, The Netherlands, Belgium, Finland) were included in the study. Revascularization was associated with lower 1-year mortality. Norway, Belgium, Spain, Poland, and Italy also had lower than expected revascularization rates but higher than expected mortality rates. France and USA had almost two times the expected rate of 7-day revascularization, which was associated with modest mortality benefits. Patients' propensity for revascularization based on clinical factors alone was associated with lower 1-year mortality (OR 0.97, 95% CI: 0.96-0.99). Country-level factors had an impact on propensity for revascularization but no impact on 1-year mortality. CONCLUSION: Our study reveals the potential for some countries with lower than expected 7-day revascularization rates to improve their clinical outcomes. Also highlighted is the possibility for more economically efficient delivery of care in USA and France.

Adult↗
PubMed2006

Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction.

AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). METHODS: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. RESULTS: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03-1.52; p=0.03) for prior AF and 1.32 (1.20-1.45; p<0.0001) for current AF. HR for major CV events was 1.15 (0.98-1.35; p=0.08) and 1.21 (1.12-1.31; p<0.0001). CONCLUSION: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.

Acute Disease↗
PubMed2006

A comparison of the clinical impact of bleeding measured by two different classifications among patients with acute coronary syndromes.

OBJECTIVES: The goal of this study was to determine the association between Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding and clinical outcomes. BACKGROUND: There are limited data on the relative utility of either scale at predicting clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (ACS). METHODS: Pooled data from two randomized trials of patients with ACS (n = 15,454) were analyzed to determine the association between TIMI and GUSTO bleeding and 30-day and 6-month death/myocardial infarction (MI) using Cox proportional hazards modeling that included bleeding as a time-dependent covariate. RESULTS: There was a stepwise increase in the adjusted hazard of 30-day death/MI with worsening GUSTO bleeding (hazard ratio [95% confidence interval], GUSTO mild 1.20 [1.05 to 1.37]; moderate 3.28 [2.88 to 3.73]; severe 5.57 [4.33 to 7.17]), and an increased risk with all three levels of TIMI bleeding (TIMI minimal 1.84 [1.63 to 2.08]; TIMI minor 1.64 [1.31 to 2.04]; major 1.45 [1.23 to 1.70]). When both bleeding scales were included in the same model, the risk with GUSTO bleeding persisted; however, the association between TIMI bleeding and outcome was no longer significant. CONCLUSIONS: Both scales identify ACS patients with bleeding complications at risk for adverse outcomes. In a model that included both definitions, the risk with GUSTO bleeding persisted while the risk with TIMI bleeding did not. This suggests that bleeding assessed with clinical criteria is more important than that assessed by laboratory criteria in terms of outcomes. Future clinical trials should consider using a combination of the GUSTO bleeding scale and the need for transfusion to assess bleeding complications.

Angina, Unstable↗
PubMed2006

Outcomes of patients in clinical trials with ST-segment elevation myocardial infarction among countries with different gross national incomes.

AIMS: To evaluate whether there is an association between 30-day mortality in patients with ST-segment elevation myocardial infarction (STEMI) included in clinical trials and country gross national income (GNI). METHODS AND RESULTS: A retrospective analysis of the databases of five randomized trials including 50 310 patients with STEMI (COBALT 7169, GIK-2 2931, HERO-2 17,089, ASSENT-2 17,005, and ASSENT-3 6116 patients) from 53 countries was performed. Countries were divided into three groups according to their GNI based on the World Bank data: low (less than 2900 US dollars), medium (between 2900 US dollars and 9000 US dollars), and high GNI (more than 9000 US dollars per capita). Baseline characteristics, in-hospital management variables, and 30-day outcomes were evaluated. A previously defined logistic regression model was used to adjust for differences in baseline characteristics and to predict mortality. The observed mortality was higher than the predicted mortality in the low (12.1 vs. 11.8%) and in the medium income groups (9.4 vs. 7.9%), whereas it was lower in the high income group (4.9 vs. 5.6%). CONCLUSION: An inverse relationship between mortality and GNI was observed in STEMI clinical trials. Most of the variability in mortality can be explained by differences in baseline characteristics; however, after adjustment, lower income countries have higher mortality than the expected.

Female↗
PubMed2006

Long-term adherence to evidence-based secondary prevention therapies in coronary artery disease.

BACKGROUND: Studies have examined the use of evidence-based therapies for coronary artery disease (CAD) in the short term and at hospital discharge, but few have evaluated long-term use. METHODS AND RESULTS: Using the Duke Databank for Cardiovascular Disease for the years 1995 to 2002, we determined the annual prevalence and consistency of self-reported use of aspirin, beta-blockers, lipid-lowering agents, and their combinations in all CAD patients and of angiotensin-converting enzyme inhibitors (ACEIs) in those with and without heart failure. Logistic-regression models identified characteristics associated with consistent use (reported on > or =2 consecutive follow-up surveys and then through death, withdrawal, or study end), and Cox proportional-hazards models explored the association of consistent use with mortality. Use of all agents and combinations thereof increased yearly. In 2002, 83% reported aspirin use; 61%, beta-blocker use; 63%, lipid-lowering therapy use; 54%, aspirin and beta-blocker use; and 39%, use of all 3. Consistent use was as follows: For aspirin, 71%; beta-blockers, 46%; lipid-lowering therapy, 44%; aspirin and beta-blockers, 36%; and all 3, 21%. Among patients without heart failure, 39% reported ACEI use in 2002; consistent use was 20%. Among heart failure patients, ACEI use was 51% in 2002 and consistent use, 39%. Except for ACEIs among patients without heart failure, consistent use was associated with lower adjusted mortality: Aspirin hazard ratio (HR), 0.58 and 95% confidence interval (CI), 0.54 to 0.62; beta-blockers, HR, 0.63 and 95% CI, 0.59 to 0.67; lipid-lowering therapy, HR, 0.52 and 95% CI, 0.42 to 0.65; all 3, HR, 0.67 and 95% CI, 0.59 to 0.77; aspirin and beta-blockers, HR, 0.61 and 95% CI, 0.57 to 0.65; and ACEIs among heart failure patients, HR, 0.75 and 95% CI, 0.67 to 0.84. CONCLUSIONS: Use of evidence-based therapies for CAD has improved but remains suboptimal. Although improved discharge prescription of these agents is needed, considerable attention must also be focused on understanding and improving long-term adherence.

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

Clinical trial issues in weight-loss therapy.

BACKGROUND: Overweight and obesity rates continue to increase nationally, generating significant interest in weight-loss therapies to address both the burden of obesity-associated chronic disease and individual concerns about appearance. Effective obesity therapies also have the potential for off-label use and unintended consequences. METHODS: The behavioral, pharmacologic, and surgical therapies for obesity are reviewed. Clinical trial issues common to chronic disease states and issues specific to obesity trials are examined. Finally, study designs for obesity therapy, including populations, control arms, sample size, and duration of therapy, are discussed.

Anti-Obesity Agents↗
PubMed2006

Cardiac tamponade in the fibrinolytic era: analysis of >100,000 patients with ST-segment elevation myocardial infarction.

BACKGROUND: Cardiac tamponade is a life-threatening complication of acute myocardial infarction (MI). Data on the incidence, risk factors, and outcome of tamponade in patients with acute MI in the fibrinolytic era are limited. METHODS: Data from a combined clinical trials database of ST-segment elevation MI were used to evaluate the incidence of cardiac tamponade, baseline characteristics, and outcomes in patients with and without tamponade. Univariable and multivariable analyses assessed the relationship between patient characteristics and tamponade development, and the influence of tamponade on mortality. RESULTS: Of 102,060 patients, 865 (0.85%) developed isolated cardiac tamponade during initial hospitalization. Patients with tamponade were older (median 71.9 vs 61.6 years, P < .001), were more likely to be female (54.0% vs 25.1%, P < .001), were more likely to have an anterior MI (61.9% vs 41.5%, P < .001), and had a longer time from symptom onset to reperfusion (median 3.5 vs 2.8 hours, P < .001) than those without tamponade. Multivariable analyses identified increasing age, anterior MI location, female sex, and increased time from symptom onset to treatment as significant independent predictors of tamponade. Patients with tamponade had an increased death rate at 30 days (hazard ratio 7.9, 95% CI 4.7-13.5). CONCLUSION: Cardiac tamponade occurs in < 1% of patients with fibrinolytic-treated acute MI and is associated with increased 30-day mortality. Time from symptom onset to treatment strongly predicted the development of tamponade, underscoring the need for continued efforts to increase speed to treatment in acute MI.

Age Factors↗
PubMed2006

Multifaceted intervention to promote beta-blocker use in heart failure.

BACKGROUND: Despite a survival benefit and guideline recommendation for beta-blockers in left ventricular systolic dysfunction, beta-blockers are underused in clinical practice. METHODS: Medical practices with > or = 15 patients with heart failure (HF) in the Duke Databank for Cardiovascular Disease (DDCD) were identified for a prospective, randomized study using a multifaceted intervention to improve beta-blocker use. Intervention practices received provider education, patient education materials, feedback on beta-blocker use of their patients with HF, and access to telephone consultation with an HF expert. The primary outcome was a comparison between intervention and control practices of the proportion of patients with HF self-reporting beta-blocker use on their first routine DDCD follow-up in the postintervention year. A random effects model was used for the analysis. RESULTS: Post intervention, 2631 patients (1701 in 23 intervention practices and 930 in 22 control practices) completed DDCD follow-up. No significant difference in the proportion of patients with HF reporting beta-blocker use was found in the intervention versus control groups (OR 1.16, 95% CI 0.94-1.43, P = .2), although more patients in the intervention group started a beta-blocker than stopped a beta-blocker during the study period (P = .02). CONCLUSIONS: This multifaceted intervention did not significantly increase the mean proportion of patients taking beta-blockers within practices exposed to the intervention, although favorable trends were observed. Further studies are needed to identify and evaluate strategies for translating evidence into clinical practice to reduce the global health burden associated with HF.

Adrenergic beta-Antagonists↗
PubMed2006

The influence of risk status on guideline adherence for patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Practice guidelines for patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) recommend targeting evidence-based therapies for the highest-risk patients. We characterized guideline adherence for NSTE ACS by risk status. METHODS: We analyzed inhospital treatments and outcomes for 77760 patients with NSTE ACS (ischemic ST-segment changes and/or positive cardiac markers) included in the CRUSADE initiative from January 2001 to September 2003 at 457 US hospitals. Compliance with the American College of Cardiology/American Heart Association Class guideline recommendations for NSTE ACS was evaluated in subgroups of eligible patients without listed contraindications at increased risk for mortality and among risk categories designated by an adapted version of the PURSUIT risk model designed to predict inhospital mortality. RESULTS: Inhospital mortality was increased in patients with diabetes mellitus (5.8% vs 4.3%), renal insufficiency (10.0% vs 3.9%), signs of congestive heart failure on presentation (10.6% vs 3.1%), and age > or = 75 years (8.6% vs 2.7%), compared with patients without these features. Use of guideline-recommended acute medications, invasive cardiac procedures, and discharge medications and interventions was significantly lower in patients with these high-risk features. Patients designated as high-risk for inhospital mortality were less likely to be treated with guideline-recommended therapies compared with low-risk and moderate-risk patients. CONCLUSIONS: Patients with NSTE ACS with the highest risk of mortality are less likely to receive guideline-recommended therapies and interventions. These findings highlight the need to clarify guideline recommendations for high-risk patients and to develop novel quality improvement approaches that target undertreated subgroups of patients with NSTE ACS.

Acute Disease↗
PubMed2006

Evaluation of diagnostic imaging technologies and therapeutics devices: better information for better decisions: proceedings of a multidisciplinary workshop.

We are entering an era in which the success of biomedical science and the increasing understanding of the value of evidence for practice are in a state of tension. This tension is especially notable in the device arena, in which the short life cycles and iterative nature of development are at odds with current design constructs of the types of clinical trials that provide evidence for medical decision making. The financial pressure arising from strained budgets and expanding costs from the aging of the population and the continued development of new technology heightens the need for a focus on new approaches. Given this background, a group of experts representing constituencies with different perspectives were convened for a day and a half to discuss key issues and their potential solutions. Because of the complex and heterogeneous nature of the environments in which devices are used, the meeting focused on 3 broad, general uses of devices: imaging, risk stratification, and therapeutics. The goal of the meeting was to develop a preliminary list of ideas that could be framed as researchable questions or constructs for consideration by policy makers that ultimately might lead to improvements in the current system. Across diagnostic imaging, risk stratification devices, and therapeutic devices, the crosscutting issues can be identified: We need better methods of collaborative funding and priority setting, improved and more flexible methods, and new approaches to the integration of federal agencies in overseeing the system.

Alzheimer Disease↗
PubMed2006

Extent of coronary artery disease as a predictor of outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) and heart failure (HF) are powerful predictors of poor outcome after acute myocardial infarction (MI). It is not known, however, whether the extent of coronary artery disease (CAD) independently influences cardiovascular (CV) outcomes in these high-risk patients. METHODS: In the VALIANT, 14703 patients were randomly assigned to receive either captopril monotherapy, valsartan monotherapy, or a valsartan and captopril combination between 0.5 and 10 days after acute MI complicated by LVSD, HF, or both. Cox proportional hazards models were used to evaluate the relation between the extent of CAD (the number of diseased vessels as assessed by angiography) and a range of CV outcomes and all-cause mortality. RESULTS: Coronary angiography data were available on 5742 (40%) of the 14703 randomized patients. Single-vessel disease was reported in 1955 patients (34%), 2-vessel disease in 1598 (28%), and 3-vessel disease in 2189 (38%). For all CV outcomes, the risk increased with the severity of CAD (P for trend < .002). A comparison of single-, 2-, and 3-vessel disease showed that, after adjusting for all known covariates, including revascularization and ejection fraction, 2-vessel disease was associated with a 40% increased hazard (P = .008) and 3-vessel disease was associated with an 85% increased hazard (P < .001) for all-cause mortality. The fully adjusted hazard ratios for death and other CV outcomes increased significantly with increasing extent of CAD. CONCLUSIONS: Increasing extent of CAD, as detected by angiography, is a significant and independent risk factor for adverse CV outcomes after MI complicated by HF, LVSD, or both. The observed risk was apparent even after excluding patients who had undergone revascularization.

Aged↗
PubMed2006

Predicting significant coronary artery disease in patients with left ventricular dysfunction.

BACKGROUND: Because coronary artery disease (CAD) is a prevalent comorbidity in patients with low ejection function (EF), a number of patients with heart failure undergo diagnostic cardiac catheterization. The objective of this study was to develop a model to assist clinicians in determining the likelihood of CAD before cardiac catheterization. METHODS: This study was a retrospective analysis using the Duke Databank for Cardiovascular Disease. From the databank, 2054 patients who underwent cardiac catheterization between 1992 and 2002 that was preceded by echocardiography with an EF of < 45% were identified. The patients' median age was 63 years, and the median EF was 30%. Patients were considered to have significant CAD if any major epicardial vessel had > or = 75% stenosis. A multivariable model of CAD was generated using stepwise logistic regression. We included demographic, clinical, electrocardiographic, and echocardiographic parameters, including segmental wall motion abnormality. RESULTS: Of the patients who met the criteria, 1184 (58%) had significant CAD and 870 (42%) did not. Significant predictors of CAD, in the order of their ability to predict significant CAD, included history of myocardial infarction, age, diabetes mellitus, Q wave on electrocardiogram, male sex, and segmental wall motion abnormality (all P < .0001). The area under the receiver operating characteristic curve was 0.865. CONCLUSIONS: By using baseline demographic and clinical characteristics, we developed a highly discriminatory diagnostic model for predicting CAD in patients with heart failure. Given the high prevalence of patients without CAD in this cohort, accurate baseline assessment of patients with left ventricular dysfunction for CAD might avoid unnecessary invasive procedures.

Cardiac Catheterization↗
PubMed2006

The prognostic value of the admission and predischarge electrocardiogram in acute coronary syndromes: the GUSTO-IIb ECG Core Laboratory experience.

BACKGROUND: Prior research suggests that patients may be entered into clinical trials with different electrocardiographic (ECG) findings than specified by study protocol criteria; the extent and impact of this variability in a large-scale trial have not been previously described. METHODS: We evaluated the relationship between case report form (CRF) categorization of the admission ECG and a Core Laboratory and subsequent outcome in a retrospective analysis of a trial of patients with acute ischemia and a broad spectrum of ECG changes (the GUSTO-IIb trial). RESULTS: In 11,037 patients with CRF information and an interpretable ECG, there was agreement in 89.1% of ST-elevation and 81.9% of non-ST-elevation cases. Among patients designated as having no ST elevation on the CRF, 1-year mortality rates were significantly higher in the subgroup of patients with Core Laboratory-determined ST elevation as compared with those where both the CRF and Core Laboratory classification were in agreement (8.8% vs 6.8%, P = .0093). Among patients designated as having ST elevation by the CRF, 1-year mortality rates were similar in both the subgroup of patients with and without Core Laboratory agreement (7.7% vs 8.2%, P = .72). CONCLUSIONS: These findings have important implications for clinicians in routine practice because even a simple evaluation (presence or absence of ST elevation) on the admission ECG was often discordant and was associated with adverse clinical outcome.

Aged↗
PubMed2006

Racial differences are seen in blood pressure response to fosinopril in hypertensive children.

BACKGROUND: Few antihypertensive therapies have been systematically studied in children and dosages for many agents are either extrapolated from adult studies or obtained from small homogenous pediatric populations. It is well established that adult patients of different races show disparate response to angiotensin-converting enzyme (ACE) inhibitors, however no such studies have been performed in children. METHODS: Two hundred fifty three children ages 6-16 with hypertension or with high normal blood pressure with an associated medical condition requiring antihypertensive therapy were enrolled at 78 clinical sites in the US, Russia, and Israel in a double blind study to evaluate the efficacy of fosinopril compared to placebo. RESULTS: The racial composition of the cohort included 60.1% white (152/253), 20.6% black (52/253), 13.8% Hispanic (35/253), 2.0% Asian (5/253), 0.4% Native American (1/253), and 3.2% (8/253) children classified as other or of mixed race. After adjusting for baseline blood pressure and body surface area (BSA) there was no significant dose response seen in non-black patients. Non-blacks randomized to the low, medium, and high dosages of fosinopril all had a mean decrease of 12 mm Hg in their sequential systolic BP (SBP). Blacks, however, demonstrated a significant dose response to fosinopril; those who received the low dosage had a 5 mm Hg decrease in SBP, and those who received the high dosage had a mean 13 mm Hg decrease in SBP. CONCLUSIONS: Fosinopril was effective in treating hypertension, but black children required a higher dose per body weight in order to achieve adequate control. This suggests that black children treated with fosinopril for hypertension on average require higher doses to achieve adequate systolic blood pressure control that non-black children.

Adolescent↗