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Robert M Califf

Publications and source records attributed to Robert M Califf.

At least 145 records · Page 8Linked to original sources
PubMed2004

Novel approaches to clinical trials: device-related infections.

The explosive growth in the use of cardiac devices and the continued large number of thoracic operations produce a significant number of costly infectious complications. These infections represent a leading cause of death and disability after device implantation or surgery. Unfortunately, few objective data are available to validate the clinical epidemiology of surgical and device-related infections, and although the number of randomized trials is increasing, too few have tested strategies for prophylaxis or treatment, particularly in the cardiac arena. Because of the expected increase in invasive vascular procedures and device implantations, it is timely to consider innovative approaches to clinical research that will hasten the translation of effective therapeutic strategies and technologies into clinical practice. Because of the multidisciplinary nature of the care of patients undergoing thoracic surgery or device implantation, bringing together existing networks and several arms of the Federal government could rapidly advance this field to provide a definitive base of evidence to guide clinical practice and improve clinical outcomes. The remainder of the articles in this supplement discuss specific issues on the diagnosis and treatment of device-related or surgical infection. The purpose of this manuscript is to discuss issues about the design of studies and their organization.

Antibiotic Prophylaxis↗
PubMed2004

Multinational economic evaluation of valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT).

BACKGROUND: The Valsartan Heart Failure Trial (Val-HeFT) compared valsartan versus placebo in 5010 patients taking prescribed background therapy for New York Heart Association class II to IV heart failure. Valsartan reduced the risk of heart failure hospitalization and improved clinical signs and symptoms of heart failure. We sought to compare resource use, costs, and health outcomes among patients taking prescribed therapy for heart failure and randomly assigned to receive valsartan or placebo. METHODS: Measures of resource use were based on data collected during the trial. Unit cost estimates were collected from individual countries and converted to 1999 US dollars. Total costs were estimated for hospitalizations, inpatient and outpatient physician services, ambulance transportation, deaths outside the hospital, and outpatient cardiovascular medications. RESULTS: Mean follow-up was 23 months. Mean costs for heart failure hospitalizations were 423 dollars lower among patients receiving valsartan (95% CI, -706 to -146). Mean total costs were 9008 dollars for patients receiving valsartan and 8464 dollars for patients receiving placebo, a net incremental cost of 545 dollars (95% CI, -149 to 1148), including the cost of valsartan. There was an overall reduction in total costs of 929 dollars (95% CI, -3243 to 1533) among patients not receiving an ACE inhibitor at baseline but a slight increase in costs of 334 dollars (95% CI, -497 to 1199) among those receiving an ACE inhibitor without a beta-blocker and a 1246 dollars increase (95% CI, 54 to 2230) in patients receiving both an ACE inhibitor and a beta-blocker at baseline. CONCLUSIONS: Valsartan provided clinical benefits at a mean incremental cost of 285 dollars per year during the trial. In patients not taking ACE inhibitors, valsartan was economically attractive, increasing survival while reducing or marginally increasing overall costs.

Adrenergic beta-Antagonists↗
PubMed2004

Incidence and characteristics of stroke during 90-day follow-up in patients stabilized after an acute coronary syndrome.

BACKGROUND: Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes (ACS). The type, outcome, and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported. METHODS: We evaluated stroke incidence, subtypes, and outcomes, in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. RESULTS: Of 15,904 stabilized patients with ACS, 113 (0.71%) had a stroke over a median follow-up of 90 days. The majority of strokes occurred within 30 days of presentation, and the time course for stroke occurrence paralleled that of myocardial (re)infarction. Most strokes were ischemic (78%), and 52% resulted in moderate or severe disability or death. Patients with stroke were older and more often had hypertension, diabetes, peripheral vascular disease, and atrial fibrillation. Among patients with stroke who had cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting, stroke occurred predominantly after the procedure. No difference in occurrence or type of stroke was observed in the assigned treatment groups. In multivariable modeling age, heart failure, prior stroke, left bundle branch block, and systolic blood pressure predicted the occurrence of stroke. CONCLUSIONS: In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and/or aspirin, stroke occurred in fewer than 1% within 90 days but carried a significant mortality and morbidity risk.

Acute Disease↗
PubMed2004

Coordinated series of studies to evaluate characteristics and mechanisms of acute coronary syndromes in high-risk patients randomly assigned to enoxaparin or unfractionated heparin: design and rationale of the SYNERGY Library.

Clinical trials and accompanying substudies in patients with acute coronary syndromes (ACS) have over the last several years yielded a wealth of knowledge about the pathophysiology and management of this high-risk condition. The Superior Yield of the New strategy of Enoxaparin, Revascularization, and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) trial is a large-scale, randomized, controlled trial evaluating the effect of enoxaparin and unfractionated heparin on death and myocardial infarction in high-risk patients presenting with non-ST-segment elevation ACS. The SYNERGY Library has been designed as a coordinated series of investigations with simultaneous data acquisition on the same cohort of approximately 500 SYNERGY patients at 60 centers in North America. Specifically, electrocardiograms, coronary arteriograms, inflammatory markers, coagulation studies, and genetic samples will be collected and processed at core laboratory facilities, and the results will be stored in a central repository. This novel strategy for substudy investigation is unprecedented in cardiovascular clinical trials. The goal is to gain significant understanding about this patient population, discover new principles of pathophysiology, identify novel pharmacologic targets, and streamline further drug development. It is hoped that the SYNERGY Library will serve as a model for future substudy design to maximize academic insight within the framework of a large-scale, multicenter trial.

Angina, Unstable↗
PubMed2004

Slowing the progression of diabetic nephropathy and its cardiovascular consequences.

This paper incorporates the findings from a multidisciplinary meeting on diabetic nephropathy and its renal and cardiovascular complications into a review article. The epidemic of obesity and the growing elderly population in the United States are primary drivers of a secondary epidemic of incipient type 2 diabetes mellitus and diabetic nephropathy. Current therapies aim to treat blood pressure, particularly with agents that block the renin-angiotensin system, to a target of 130/80 mm Hg. However, even lower blood pressure targets may be optimal. Control of hyperglycemia and dyslipidemia, smoking cessation, exercise, and weight loss all compliment blood pressure control and are achieved most effectively when the patient, provider, and health system are aligned with these goals. Once end-stage renal disease (ESRD) is reached, patients enter the highest cardiovascular risk-state appreciated in human medicine. Because of uniform access to care in the United States, advanced data systems, and circulatory system (intravascular) access in most patients, the ESRD population should be the future sampling frame for newer treatments tested in both prospective cohort and randomized trials. Cardiorenal risk, or the degree of excess cardiovascular risk incurred by patients with chronic kidney disease and ESRD, is a state offering considerable research opportunities for novel cardiovascular risk factors. Future studies should fully consider the possibility that improved outcomes would be achieved at a greater cost; thus, cost-effectiveness studies are essential for understanding the economic aspects of implementation. The goal of an ideal clinical trial would be ESRD prevention; however, pragmatic objectives such as a greater understanding of therapeutic toxicities should also be explored in this population.

Albuminuria↗
PubMed2004

Cardiovascular disease and chronic kidney disease: insights and an update.

Despite the high prevalence and significant morbidity and mortality rates of chronic kidney disease (CKD) related to cardiovascular disease, it remains vastly understudied. Most of the current practice recommendations come from small under-powered prospective studies, retrospective reviews, and assuming patients with CKD will similarly benefit from medications and treatments as patients with normal renal function. In addition, because of the previous lack of a consistent definition of CKD and how to measure renal function, definitions of the degree of renal dysfunction have varied widely and compounded the confusion of these data. Remarkably, despite patients with CKD representing the group at highest risk from cardiovascular complications, even greater than patients with diabetes mellitus, there has been a systematic exclusion of patients with CKD from therapeutic trials. This review outlines our current understanding of CKD as a cardiovascular risk factor, treatment options, and the future directions that are needed to treat cardiovascular disease in patients with CKD.

Cardiovascular Diseases↗
PubMed2004

Prognostic value of predischarge electrocardiographic measurement of infarct size after thrombolysis: insights from GUSTO I Economics and Quality of Life substudy.

BACKGROUND: Current methods for risk stratification after acute myocardial infarction (MI) include several noninvasive studies. In this cost-containment era, the development of low-cost means should be encouraged. We assessed the ability of an electrocardiogram (ECG) MI-sizing score to predict outcomes in patients enrolled in the Economics and Quality of Life (EQOL) sub study of the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries -I (GUSTO-I) trial. METHODS: We classified patients by electrocardiographic Selvester QRS score at hospital discharge: those with a score 0-9 versus > or =10. Endpoints were 30-day and 1-year mortality, resource use, and quality-of-life measures. RESULTS: Patients with a QRS score <10 were well-matched with those with QRS score > or =10 with the exception of a trend to more anterior MI in the higher scored group. Patients with QRS score > or =10 had increased risk of death at 30-days (8.9% vs. 2.9% P < .001), and this difference persisted at 1 year (12.6% vs. 5.4%, P = .001). Recurrent chest pain, use of angiography, and angioplasty were similar during follow-up. However, there was a trend toward less coronary bypass surgery in patients with a QRS score > or =10. Readmission rates were higher at 30 days but similar at 1 year. CONCLUSIONS: Stratification of patients after acute MI by a simple measure of MI size identifies populations with different long-term prognoses; patients with a QRS score > or =10 (approximately 30% of the left ventricle infarcted) at discharge have poorer outcomes in both the short- and long-term. The standard 12-lead ECG provides a simple, economical means of risk stratification at discharge.

Electrocardiography↗
PubMed2004

Risk stratification after hospitalization for decompensated heart failure.

BACKGROUND: Decompensated heart failure (HF) is among the most common indications for hospitalization in the United States, but little is known about features on admission that predict adverse events. We used data from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study to develop a model that would predict outcomes in patients with decompensated HF. METHODS AND RESULTS: OPTIME-CHF randomized 949 patients hospitalized with decompensated HF for 48 to 72 hours of infusion of either milrinone or placebo. We used multivariable modeling to evaluate variables on admission that would be predictive of 60-day mortality or the composite of death or rehospitalization at 60 days. Variables at presentation that predicted death at 60 days were increased age, lower systolic blood pressure, New York Heart Association class IV symptoms, elevated blood urea nitrogen (BUN), and decreased sodium. Predictors of the composite of death or rehospitalization within 60 days were the number of HF hospitalizations in the preceding 12 months, elevated BUN, lower systolic blood pressure, decreased hemoglobin, and a history of percutaneous coronary intervention (PCI). The discriminatory power of the model was substantial for the mortality model (c-index .77) but less for the composite endpoint (c-index .69). CONCLUSIONS: Risk stratification of patients with decompensated HF may be accomplished using easily assessed clinical variables. Further research into the validity of this model in independent samples will potentially aid in the development of risk stratification strategies.

Aged↗
PubMed2004

Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial.

AIMS: In high risk patients with non-ST elevation acute coronary syndromes (ACS), enoxaparin is generally preferred to unfractionated heparin (UFH). However, less is known about the relative merits of these two forms of heparin in patients receiving concomitant glycoprotein IIb/IIIa inhibitors. METHODS AND RESULTS: The A phase of the A-to-Z trial was an open label non-inferiority trial in which 3987 patients with non-ST elevation ACS were randomised to receive either enoxaparin or UFH in combination with aspirin and tirofiban. Inclusion required either ST depression or cardiac biomarker elevation. While the selection of an early management strategy (invasive or conservative) was at the discretion of the local investigator, investigators were asked to designate their plans for an invasive or conservative strategy on the case record form. An early conservative strategy was specified for 1778 patients (45%); this subgroup forms the population for the present analyses. Among patients with a planned conservative strategy, baseline characteristics were similar between those randomised to UFH (n = 872) and those randomised to enoxaparin (n = 906). The primary endpoint of death, new MI, or documented refractory ischaemia within 7 days of randomisation occurred in 10.6% of patients randomised to UFH and 7.7% of patients randomised to enoxaparin (HR 0.72; 95% CI 0.53-0.99; p = 0.04). The combined rate of TIMI major, minor, or loss no-site bleeding was 1.3% in patients treated with UFH and 1.8% in those treated with enoxaparin (p = ns). CONCLUSIONS: When a conservative approach to catheterisation and PCI was planned for ACS patients receiving tirofiban and aspirin, enoxaparin was associated with superior efficacy and similar bleeding vs UFH.

Aspirin↗
PubMed2004

An international perspective on heart failure and left ventricular systolic dysfunction complicating myocardial infarction: the VALIANT registry.

AIMS: We analysed the contemporary incidence, outcomes, and predictors of heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) before discharge in patients with acute myocardial infarction (MI). The baseline presence of HF or LVSD, or its development during hospitalisation, increases short- and long-term risk after MI, yet its incidence, predictors, and outcomes have not been well described in a large, international, general MI population. METHODS AND RESULTS: The VALIANT registry included 5573 consecutive MI patients at 84 hospitals in nine countries from 1999 to 2001. A multivariable logistic survival model was constructed using baseline variables to determine the adjusted mortality risk for those with in-hospital HF and/or LVSD. Baseline variables were also tested for associations with in-hospital HF and/or LVSD. Of the 5566 patients analysed, 42% had HF and/or LVSD during hospitalisation. Their in-hospital mortality rate was 13.0% compared with 2.3% for those without HF and/or without LVSD. After adjustment for other baseline risk factors, in-hospital HF and/or LVSD carried a hazard ratio for in-hospital mortality of 4.12 (95% confidence interval: 3.08-5.56). Patients with HF and/or LVSD also had disproportionately higher rates of other cardiovascular events. CONCLUSIONS: HF and/or LVSD is common in the general contemporary MI population and precedes 80.3% of all in-hospital deaths after MI. Survivors of early MI-associated HF and/or LVSD have more complications, longer hospitalisations, and are more likely to die during hospitalisation. Although baseline variables can identify MI patients at highest risk for HF and/or LVSD, such patients are less likely to receive indicated procedures and medical therapies.

Female↗
PubMed2004

Postmenopausal hormone use in women with acute coronary syndromes.

BACKGROUND: Recent trials reveal no benefit and possible harm from chronic hormone replacement therapy (HRT). Less is known about intermediate-term outcomes associated with HRT use in the setting of acute coronary syndromes (ACS). METHODS: To examine the prevalence of HRT use and relationships with intermediate-term outcomes among women with ACS, we classified as HRT users or nonusers 4029 postmenopausal women (age > 50 years or postmenopausal by case report form) randomized in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-Acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. Outcomes included 90-day and 1-year death and 90-day stroke, death, or myocardial infarction (MI); death, MI, or stroke; and death, MI, or severe recurrent ischemia (SRI). RESULTS: HRT use was 13% overall and varied by region (Asia, 0%; Eastern Europe, 0.2%; Latin America, 0.8%; Western Europe, 4%; Australia/New Zealand, 12%; Canada, 14%; United States, 24%); estrogen-only regimens were most common (90%). HRT users were younger, had higher estimated creatinine clearance, more frequently were smokers and had prior revascularization, but less frequently had diabetes, prior angina, or heart failure. Unadjusted 90-day and 1-year mortality rates were lower among HRT users (hazard ratios [95% CI] 0.48 [0.23-0.98] and 0.35 [0.18-0.68], respectively) but after multivariable adjustment, were not significantly different. Ninety-day stroke and composite end points did not differ between HRT users and nonusers. CONCLUSIONS: HRT use (predominantly estrogen-only) was low among patients with ACS but varied by region and was not associated with improved intermediate-term outcomes. These results are consistent with the absence of benefit from HRT use (combination or estrogen only) in previous studies in more stable populations.

Aged↗
PubMed2004

Six-month outcomes of percutaneous coronary balloon angioplasty in acute coronary syndromes: Results from the PURSUIT trial.

BACKGROUND: Potent inhibition of the platelet glycoprotein IIb/IIIa receptor has improved the acute outcome of patients presenting with acute coronary syndromes (ACS). For patients with ACS undergoing percutaneous balloon angioplasty without coronary stenting in the era of platelet glycoprotein IIb/IIIa blockade, the long-term prognosis is less clear. OBJECTIVE: To examine the six-month outcome of patients who received eptifibatide within a randomized clinical trial and subsequently underwent balloon angioplasty. METHODS: Patients included in this substudy were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, a randomized study evaluating the efficacy of eptifibatide in reducing the incidence of death or nonfatal myocardial infarction (MI) in non-ST segment elevation ACS. During the index hospitalization, 1151 (12.2%) of the PURSUIT patients underwent percutaneous balloon angioplasty without coronary stenting. RESULTS: Eptifibatide was associated with a significant reduction in the adjudicated composite end point of death or MI at six months after randomization in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (P=0.037). A trend toward a beneficial effect was evident before the procedure (4.7% versus 6.9%; P=0.13) and at 30 days (12.1% versus 15.3%; P=0.12). The incidence of repeat revascularization was relatively low for patients undergoing PTCA, with no difference observed between the eptifibatide and placebo groups (16.3% versus 14.8%; P=0.51). CONCLUSIONS: Eptifibatide was associated with a sustained beneficial effect to six months in patients with ACS undergoing PTCA. It reduced the incidence of preprocedural MI. The rate of repeat revascularization at six months was low and was not significantly altered by eptifibatide.

Acute Disease↗
PubMed2004

A comparison of clinical outcomes between Canadian and American patients after nonurgent coronary stenting.

BACKGROUND: Practice patterns for percutaneous coronary interventions (PCIs) may differ between Canada and the United States. Few data are available comparing PCI outcomes between the two countries in the era of coronary stenting and adjunctive glycoprotein IIb/IIIa inhibition. METHODS: In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, 2064 patients were randomly assigned to receive eptifibatide or placebo during nonurgent PCI. The 30-day and one-year rates of death, myocardial infarction (MI) and target vessel revascularization (TVR) were compared between Canadian and American patients enrolled in the ESPRIT trial. RESULTS: There were 1531 American patients and 533 Canadian patients enrolled. Americans were older and heavier, and had a higher incidence of cardiac risk factors than Canadians (P<0.05 for all variables). Canadian patients had a lower incidence of death, MI and TVR at 30 days (6.2% versus 10.4%, P=0.004) and at one year (14.8% versus 21.5%, P=0.0006). After adjusting for known baseline differences, enrollment in Canada remained a significant predictor of reduced ischemic complications at 30 days (OR=0.53, c2=9.0, P=0.003). Similar results were observed at one year. Eptifibatide was superior to placebo in both groups of patients. CONCLUSIONS: This analysis is among the first to show Canadian patients to have fewer adverse events than American patients after nonurgent PCI. This effect was independent of known baseline differences between the patients in each country. The relative treatment effect of eptifibatide in Canadian patients paralleled that observed in the main ESPRIT trial and in American patients.

Aged↗
PubMed2003

Prognostic importance of new small Q waves following non-ST-elevation acute coronary syndromes.

PURPOSE: To investigate the prognostic importance of new small Q waves following an acute coronary syndrome. METHODS: We assessed 6-month mortality in 10501 patients with non-ST-elevation acute coronary syndromes who had survived 30 days and had both admission and 30-day electrocardiograms. Patients were stratified by whether they had no new Q waves (n = 9447), new 30- to 40-ms Q waves (n = 733), or new > or =40-ms Q waves (n = 321). RESULTS: Mortality was higher in patients with 30- to 40-ms Q waves than in those with no new Q waves (3.4% [25/733] vs. 2.4% [227/9447], P = 0.005), and even higher in those with > or =40-ms Q waves (5.3% [17/321], P = 0.002). After adjustment for baseline risk predictors, mortality remained higher in patients with new 30- to 40-ms Q waves (odds ratio [OR] = 1.30; 95% confidence interval [CI]: 0.85 to 1.98; P = 0.23) and those with new > or =40-ms Q waves (OR = 1.87; 95% CI: 1.13 to 3.09; P = 0.01). CONCLUSION: Patients with new small Q waves following a non-ST-elevation acute coronary syndrome are at increased risk of adverse outcomes. These small Q waves should be considered diagnostic of myocardial infarction. Further research should investigate whether even smaller QRS changes are prognostically important.

Acute Disease↗