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Biomedical subjects

Robert M Califf

Publications and source records attributed to Robert M Califf.

At least 127 records · Page 7Linked to original sources
PubMed2004

Aspirin dose and six-month outcome after an acute coronary syndrome.

OBJECTIVES: This study was designed to compare the efficacy of low and intermediate aspirin doses in acute coronary syndromes. BACKGROUND: Little is known of the comparative efficacy of low and intermediate aspirin doses in this setting. METHODS: We compared six-month death, myocardial infarction (MI), and stroke in patients with unstable angina or acute MI discharged while receiving low (<150 mg) or intermediate (> or =150 mg) aspirin therapy in the GUSTO IIb and PURSUIT trials (n = 20,521). We used multivariable analysis and performed a propensity analysis in order to adjust for baseline imbalances between the groups. RESULTS: Aspirin doses <150 mg were prescribed to 29.9% (6,128) of patients. By six months, 6.4% of the patients (1,310 of 20,521) had a primary event, 6.2% of the patients receiving <150 mg and 6.6% of the patients receiving aspirin doses > or =150 mg (hazard ratio [HR] 1.06 [95% confidence interval (CI) 0.94 to 1.19], p = 0.35). After adjusting for baseline imbalances and the propensity score for discharge aspirin dose, there was no effect of aspirin dose on the composite end point at six months (HR 0.92 [95% CI 0.79 to 1.07], p = 0.28). However, the higher aspirin dose was associated with a reduction in six-month MI (HR 0.79 [95% CI 0.64 to 0.98], p = 0.03). The outcome was similar when patients were matched on the basis of the propensity score for aspirin dose (HR for death/MI/stroke 0.94 [95% CI 0.80 to 1.12], p = 0.51), although stroke occurred significantly more frequently among patients receiving the higher aspirin dose (HR 1.74 [95% CI 1.01 to 3.02] p = 0.05) and the effect on MI was no longer apparent. CONCLUSIONS: Although these data are non-randomized, they suggest that the aspirin dose upon discharge may influence the clinical course after unstable angina or acute MI.

Aged↗
PubMed2004

Meta-analysis of randomized trials of percutaneous transluminal coronary angioplasty versus atherectomy, cutting balloon atherotomy, or laser angioplasty.

OBJECTIVES: We conducted a systematic overview (meta-analysis) of randomized trials of balloon angioplasty versus coronary atherectomy, laser angioplasty, or cutting balloon atherotomy to evaluate the effects of plaque modification during percutaneous coronary intervention. BACKGROUND: Several mechanical approaches have been developed that ablate or section atheromatous plaque during percutaneous coronary interventions to optimize acute results, minimize intimal injury, and reduce complications and restenosis. METHODS: Sixteen trials (9,222 patients) constitute the randomized controlled experience with atherectomy, laser, or atherotomy versus balloon angioplasty with or without coronary stenting. Each trial tested the hypothesis that ablative therapy would result in better clinical or angiographic results than balloon dilation alone. RESULTS: Short-term death rates (<31 days) were not improved by the use of ablative procedures (0.3% vs. 0.4%, odds ratio [OR] 0.94 [95% confidence interval 0.46 to 1.92]), but periprocedural myocardial infarctions (4.4% vs. 2.5%, OR 1.83 [95% CI 1.43 to 2.34]) and major adverse cardiac events (5.1% vs. 3.3%, OR 1.54 [95% CI 1.25 to 1.89]) were increased. Angiographic restenosis rates (6,958 patients) were not improved with the ablative devices (38.9% vs. 37.4%, OR 1.06 [95% CI 0.97 to 1.17]). No reduction in revascularization rates (25.2% vs. 24.5%, OR 1.04 [95% CI 0.94 to 1.14]) or cumulative adverse cardiac events rates up to one year after treatment were seen with ablative devices (27.8% vs. 26.1%, OR 1.09 [95% CI 0.99 to 1.20]). CONCLUSIONS: The combined experience from randomized trials suggests that ablative devices failed to achieve predefined clinical and angiographic outcomes. This meta-analysis does not support the hypothesis that routine ablation or sectioning of atheromatous tissue is beneficial during percutaneous coronary interventions.

Angioplasty, Balloon, Coronary↗
PubMed2004

Feasibility of endovascular cooling as an adjunct to primary percutaneous coronary intervention (results of the LOWTEMP pilot study).

In a nonrandomized feasibility study of therapeutic hypothermia in acute myocardial infarction, 18 patients were treated with endovascular cooling (Alsius, Irvine, California) as adjunctive therapy to primary percutaneous coronary intervention to assess measures of infarct size (area under the curve creatinine kinase-MB and technetium-99m single-photon emission computed tomography sestamibi) and the quality of myocardial perfusion (continuous ST-segment monitoring). Periprocedural endovascular cooling successfully decreased core body temperature (median 33.5 degrees C) and was well tolerated, which supports the evaluation of adjunctive hypothermia in pivotal trials to limit infarct size and decrease reperfusion injury.

Angioplasty, Balloon, Coronary↗
PubMed2004

Outcome of acute ST-segment elevation myocardial infarction in diabetics treated with fibrinolytic or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: lessons from the GUSTO V trial.

OBJECTIVES: We studied the outcome of diabetics enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) V trial to assess whether the combination of half-dose reteplase and abciximab provides any propitious benefits over standard fibrinolytic therapy in diabetic patients. BACKGROUND: Diabetics with acute ST-segment elevation myocardial infarction (MI) have a worse outcome compared with nondiabetics. Higher-risk patients are usually more likely to benefit from advances in medical therapy. METHODS: We analyzed diabetic patients enrolled in the GUSTO V trial to assess the outcome of those randomized to the combination of half-dose reteplase and abciximab versus those randomized to reteplase. We also evaluated whether any differences existed in presentation and outcome of MI among the diabetics versus the nondiabetics enrolled in the study. RESULTS: The trial enrolled 13782 nondiabetics and 2633 diabetics. Compared to nondiabetics, diabetics had a significantly higher mortality at 30 days (8.5% vs. 5.1%, p < 0.001) and at 1 year (12.7% vs. 7.5%, p < 0.001). Among the diabetic subset, no significant difference existed in the incidence of 30-day (8.8% vs. 8.2%, p = 0.52) or 1-year mortality (13.0% vs. 12.4%, p = 0.62) among patients randomized to reteplase compared to those receiving combination of abciximab and reteplase. The incidence of reinfarction (2.5% vs. 4.3%, p = 0.013), recurrent ischemia (11.8% vs. 14.9%, p = 0.017), and urgent revascularization (10.9% vs. 13.3%, p = 0.055) at seven days was lower in diabetics treated with the combination therapy. CONCLUSIONS: Compared to nondiabetics, diabetics continue to have a worse outcome with MI. Although combination therapy did not provide a survival benefit, nonfatal ischemic outcomes, including reinfarction, recurrent ischemia, and urgent revascularization, were substantially reduced.

Abciximab↗
PubMed2004

Risk factors for intracranial hemorrhage and nonhemorrhagic stroke after fibrinolytic therapy (from the GUSTO-i trial).

Of 592 patients in the Global Utilization of Streptokinase and tPA for Occluded Arteries-I trial who had a stroke during initial hospitalization, the risk for intracranial hemorrhage was significantly greater in those with recent facial or head trauma (odds ratio 13.0, 95% confidence interval 3.4 to 85.5); dementia was additionally associated with an increased risk for intracranial hemorrhage (odds ratio 3.4, 95% confidence interval 1.2 to 10.2). Because facial or head trauma may greatly influence treatment decisions, this risk factor should be incorporated into models designed to estimate the risks and benefits of fibrinolytic therapy.

Aged↗
PubMed2004

International differences in evolution of early discharge after acute myocardial infarction.

BACKGROUND: Early discharge of low-risk patients with acute myocardial infarction is feasible and can be achieved at no additional risk of adverse events. We aimed to identify the extent to which countries have taken advantage of the opportunity for early discharge. METHODS: The study population consisted of 54174 patients enrolled in GUSTO-I, GUSTO-III, and ASSENT-2 studies (enrollment period 1990-98) in the USA, Canada, Australia, New Zealand, Belgium, France, Germany, Spain, and Poland. We identified patients with uncomplicated acute myocardial infarction who were eligible for early discharge on the basis of previously established criteria, and assessed the extent to which these patients were discharged early--defined as discharged alive within 4 days of admission. The economic consequences (defined as potentially unnecessary hospital days consumed per 100 patients enrolled) were also investigated. FINDINGS: Patients in all European countries had significantly longer stays than did those from non-European countries. Over the study period, the number of eligible patients discharged on or before day 4 increased in the USA, Canada, Australia, and New Zealand. Despite this increase, no more than 40% of patients who were eligible for early discharge were actually discharged early. The rate of early discharge of eligible patients was consistently low (<2%) in Belgium, France, Germany, Spain, and Poland. In ASSENT-2, which is the most recent trial in this study, the number of potentially unnecessary hospital days (per 100 patients enrolled) ranged from 65 in New Zealand to 839 in Germany. INTERPRETATION: Despite more than a decade of research, there is still a lot of variation between countries in international length-of-stay patterns in acute myocardial infarction. The potential for more efficient discharge of low-risk patients exists in all countries investigated, but was especially evident in the European countries included in the study (Belgium, France, Germany, Spain, and Poland).

Acute Disease↗
PubMed2004

Differential treatment benefit of platelet glycoprotein IIb/IIIa inhibition with percutaneous coronary intervention versus medical therapy for acute coronary syndromes: exploration of methods.

BACKGROUND: Although many believe that platelet glycoprotein IIb/IIIa inhibitors should be used only in acute coronary syndrome patients undergoing percutaneous coronary intervention, supporting data from randomized clinical trials are tenuous. The assumption that these agents are useful only in conjunction with percutaneous coronary intervention is based primarily on inappropriate subgroup analyses performed across the glycoprotein IIb/IIIa inhibitor trials. METHODS AND RESULTS: We describe the problems with these analytical techniques and demonstrate that different approaches to the question can result in opposing answers. CONCLUSIONS: Clinical-practice decisions and practice guidelines should be based on overall trial results and not analyses of post-randomization subgroups.

Acute Disease↗
PubMed2004

Economic effects of beta-blocker therapy in patients with heart failure.

PURPOSE: Studies suggest that beta-blockers improve outcomes in heart failure patients and may be cost saving to society. However, many heart failure patients are not treated with beta-blockers. Economic incentives facing hospitals, physicians, payers, and patients may not encourage treatment adoption. We assessed the economic effects of beta-blocker therapy from various perspectives: societal, Medicare, hospital, physician, and patient. METHODS: A Markov model of heart failure progression over 5 years was developed. Transition probabilities and the effect of beta-blockers on mortality and hospitalization were based on clinical trial data. Estimates of hospital costs and reimbursement were obtained from the Duke University Medical Center. Physician fees were based on the Medicare fee schedule. RESULTS: Beta-blocker therapy increased survival by 0.3 years per patient and reduced societal costs by US dollars 3959 per patient over 5 years. Medicare costs declined by US dollars 6064 per patient, due primarily to lower hospitalization rates. Unless heart failure admissions could be replaced with other hospitalizations that generated an equal or greater revenue above variable cost, hospital revenue would be negatively affected. Physician revenue from treating heart failure patients would also decline. Patient costs increased with beta-blocker use (US dollars 2113 over 5 years). CONCLUSION: Beta-blocker therapy improves the clinical outcomes of heart failure patients and is cost saving to society and Medicare. However, hospitals and physicians have no clear financial incentives to support increased beta-blocker use. Changes in practice patterns could be encouraged by linking reimbursement with evidence-based care and covering patients' medication costs.

Adrenergic beta-Antagonists↗
PubMed2004

Integrating antithrombin and antiplatelet therapies with early invasive management for non-ST-segment elevation acute coronary syndromes.

Non-ST-segment elevation acute coronary syndromes are a dramatic manifestation of coronary artery disease. Multiple clinical trials have shown that early cardiac catheterization improves clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes. Many antithrombotic agents effectively manage unstable coronary syndromes and serve as adjuncts to percutaneous coronary intervention. Yet, the growing number of pharmacologic agents makes early management of non-ST-segment elevation acute coronary syndromes increasingly complex. We review the current evidence regarding the optimal integration of early antithrombotic and antiplatelet therapies with early coronary angiography and subsequent revascularization.

Algorithms↗
PubMed2004

Antibodies to platelet factor 4/heparin are associated with elevated endothelial cell activation markers in patients with acute coronary ischemic syndromes.

BACKGROUND: We postulated that antibodies to platelet factor 4/heparin complex lead to a heightened inflammatory state, contributing to an increased risk of recurrent thrombotic events. METHODS: We analyzed serum from a subset of patients in the placebo/unfractionated heparin arm of the GUSTO IV-ACS trial who had prior heparin exposure. We selected 109 patients with the 30 day primary endpoint (death, MI or revascularization) and an equal number of controls, excluding patients with thrombocytopenia. Anti-platelet factor 4/heparin antibodies and inflammatory markers (sVCAM-1, sICAM-1, sE-selectin, sP-selectin, us-CRP, IL-6) were measured on serum samples. RESULTS: Patients with anti-PF4/heparin antibodies were more likely to have death or MI (30.4% vs. 11.3%, p = 0.01), or MI (21.7% vs. 6.2%, p = 0.01) than patients who were antibody negative. In a multiple logistic regression model that included inflammatory markers and clinical risk factors, antibody to PF4/heparin was a strong predictor of 30 day MI (odds ratio: 9.0; 95% confidence intervals 2.1-38.6; p < 0.01), with IL-6 being the only other predictor (odds ratio: 1.1; 95% confidence intervals 1.0-1.2; p = 0.03). Antibody positive patients had higher levels of sVCAM-1 (892 +/- 263 microg/l versus 780 +/- 228 microg/l; p = 0.04) and sICAM-1(246 +/- 50 microg/l versus 222 +/- 71microg/l; p = 0.02) than antibody-negative patients. CONCLUSIONS: Antibodies to the platelet factor 4/heparin complex were associated with elevated levels of endothelial but not platelet activation markers, or markers of a systemic inflammatory state. Anti-PF4/heparin antibodies were associated with a 9-fold increased risk of recurrent MI at 30 days. We measured soluble cell adhesion molecules, CRP and IL-6 from 218 non-thrombocytopenic patients, 23 of whom had antibodies to PF4/heparin. Antibody positive patients had higher levels of sVCAM-1 (892 +/- 263 microg/l versus 780 +/- 228 microg/l; p = 0.04) and sICAM-1(246 +/- 50 microg/l versus 222 +/- 71 microg/l; p = 0.02). In a multiple logistic regression model, antibody to PF4/heparin was a predictor of 30 day MI (odds ratio: 9.0; 95% CI: 2.1-38.6; p < 0.01). The presence of antibodies to PF4/heparin, even in the absence of thrombocytopenia, is a stronger predictor of 30 day MI than clinical variables or inflammatory markers.

Acute Disease↗
PubMed2004

Dynamic prognostication in non-ST-elevation acute coronary syndromes: insights from GUSTO-IIb and PURSUIT.

BACKGROUND: Risk assessment in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) traditionally focuses on and is limited to admission findings. The objective of the current study was to develop an approach to predicting outcome in NSTE-ACS that could account for the changing nature of risk. METHODS: In 7294 of 8010 patients with NSTE-ACS and complete electrocardiographic data in the GUSTO-IIb trial, we predicted the mortality probability at days 0-2, 0-30, 3-30, 5-30, and 7-30 using multiple logistic regression. Resulting risk estimates were incorporated into a composite, dynamic model to estimate the effects of changing probabilities over time. These models were validated against an independent sample of 9461 patients from the PURSUIT trial. RESULTS: As time passed after admission, the risk of 30-day death declined in stable patients. This risk, which was 3.72% at baseline, declined to 1.92% in 6-day survivors, and the risk reduction was greatest for those with the highest baseline risk. Importantly, however, the development of inhospital complications modified these trends. The use of dynamic models not only allowed us to estimate early (<48 h) mortality with a high degree of accuracy (C-index of 0.87), but also to continuously update the longer-term prognosis with increasing accuracy: the C-index increased from 0.75 for the day 0-30 model to 0.81 and 0.82 for the composite and day 7-30 models, respectively. CONCLUSIONS: Dynamic risk assessment is feasible and reliable. This approach can improve risk assessment and provide valuable guidance for management of patients with NSTE-ACS.

Age Factors↗
PubMed2004

Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.

BACKGROUND: Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of "insulin provision" versus "insulin sensitization" among patients with CAD remains unclear. METHODS: To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. RESULTS: Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.

Aged↗
PubMed2004

Improved clinical outcomes with abciximab therapy in acute myocardial infarction: a systematic overview of randomized clinical trials.

BACKGROUND: Investigations of glycoprotein (GP) IIb/IIIa inhibition in primary percutaneous coronary intervention (PCI) have suggested the efficacy of abciximab in improving clinical and angiographic outcomes, but sample-size limitations and variability in trial design preclude the ability to generalize these results to a broader patient population. METHODS: Meta-analytic techniques were used to evaluate clinical outcomes from randomized trials comparing GP IIb/IIIa inhibition with placebo or control therapy in primary PCI for acute myocardial infarction (MI). RESULTS: In 3266 patients, treatment with abciximab significantly reduced the 30-day composite end point of death, reinfarction, or ischemic or urgent target-vessel revascularization (TVR; odds ratio [OR], 0.54; 95% CI, 0.40-0.72), with trends toward reduced 30-day death and death or reinfarction. Abciximab resulted in an increased likelihood of major bleeding (OR, 1.74; 95% CI, 1.11-2.72). By 6 months, abciximab significantly reduced the occurrence of death, reinfarction, or any TVR (OR, 0.80; 95% CI, 0.67-0.97), and there were positive trends favoring a decrease in mortality alone and the composite of death or reinfarction. CONCLUSIONS: Treatment with abciximab significantly reduces early adverse ischemic events, a clinical benefit that is maintained at 6-month follow-up. These findings support the use of adjunctive GP IIb/IIIa inhibition in primary PCI.

Abciximab↗
PubMed2004

Combining baseline clinical descriptors and real-time response to therapy: the incremental prognostic value of continuous ST-segment monitoring in acute myocardial infarction.

BACKGROUND: Clinical descriptors and ST-segment recovery variables hold prognostic information for clinical outcome after thrombolysis for acute myocardial infarction (MI). We sought to define the incremental prognostic value of continuous 12-lead ST-segment monitoring variables to clinical risk descriptors identified by the Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO-I) trial 30-day mortality analysis. METHODS: Of 1,777 patients enrolled in continuous ST-segment substudies from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-9), GUSTO-I, Duke University Clinical Cardiology Study (DUCCS-II), Integrilin to manage Platelet Aggregation to Combat Thrombus in Acute Myocardial Infarction (IMPACT-AMI), Promotion of Reperfusion by Inhibition of Thrombin During Myocardial Infarction Evolution (PRIME), and Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) trials, 825 patients qualified for assessment of time to recovery. ST recovery variables analyzed were time to stable ST-recovery and late ST elevation. Patients who were at low clinical risk (n = 261) had no high-risk descriptors, and patients at high clinical risk (n = 564) had at least 1 of these high-risk descriptors: age >or=70 years, systolic blood pressure or=90 beats/min, anterior MI, or previous MI. High (n = 90), moderate (n = 318), and low (n =417) ST-risk groups were defined by the presence of both slow ST recovery and late ST elevation, one or the other, or neither, respectively. End points analyzed were inhospital death and combined death, reinfarction, or congestive heart failure. RESULTS: There was a trend toward increased mortality rate in the high-clinical/high-ST-risk group. For the composite end point, ST subgrouping resulted in significant event stratification in both patients at low and high clinical risk. In multivariable analysis, age and heart rate were independent predictors of both mortality and the composite end point. Late ST elevation added incremental prognostic information. CONCLUSION: Age, heart rate, and late ST elevation are powerful, independent predictors of adverse clinical outcome. Continuous monitoring allows noninvasive assessment of the response to therapy. Consequently, this technique will enhance the potential to risk-stratify individual patients in a real-time setting.

Aged↗
PubMed2004

Economic impact of drug-eluting stents on hospital systems: a disease-state model.

BACKGROUND: Drug-eluting intracoronary stents decrease restenosis and later revascularization. The US Department of Health and Human Services (HHS), recognizing the financial and clinical impact of this technology, recently proposed accelerated reimbursement to hospitals. METHODS AND RESULTS: A disease state-transition computer model simulated the clinical and economic consequences to hospitals of drug-eluting stents over 5 years. Model parameters combined information from a longitudinal clinical database, a hospital cost-accounting system, and a survey instrument. Simulations were repeated 1000 times for each set of parameters. With 85% of stent procedures shifted to drug-eluting stents in the first year of availability, the mean number of repeat revascularizations dropped by 60.4% at year 5. With no changes in reimbursement policy, a hospital with a catheterization laboratory volume of 3112 patients yearly converted from a 2.01 million dollars (M) annual profit to an 8.10 M dollars loss in the first year (95% CI 8.09 M dollars to 8.12 M dollars) and 8.7 M dollars annual losses in later years. This represented an overall change in cash flow of 55.71 M dollars (95% CI 55.66 M dollars to 55.76 M dollars) away from the hospital over 5 years. The incremental reimbursement proposed by HHS reduced this loss to 4.75 M dollars in the first year and to 5.6 M dollars annually thereafter. In sensitivity analyses, the conversion of patients from bypass surgery to drug-eluting stents was the largest driver of overall cash flow shifts. CONCLUSIONS: Although Medicare has proposed to increase reimbursement to ease the impact of drug-eluting stents on hospitals, this increase will not totally offset the costs.

Angioplasty, Balloon, Coronary↗