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Eric J Topol

Publications and source records attributed to Eric J Topol.

At least 253 records · Page 14Linked to original sources
PubMed2002

Glycoprotein IIb-IIIa inhibition with abciximab and postprocedural risk assessment: lessons from the evaluation of platelet IIb/IIIa inhibitor for stenting trial and implication for ad hoc use of glycoprotein IIb-IIIa antagonists.

BACKGROUND: Angiographic features of vessels in which stents have been deployed can be used to predict the risk of postprocedural ischemic events. The purpose of this study was to compare the effects of abciximab in patients with and without high-risk postprocedure features. METHODS AND RESULTS: Protocol-mandated stent implantation was performed in 1586 patients in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting trial, 783 of whom received abciximab, and was successful in 97% of the patients. High-risk features were defined as the presence of Thrombolysis In Myocardial Infarction (TIMI) flow <3, presence of thrombus or major dissection, or residual stenosis >10%. The primary endpoint was a composite of death, myocardial infarction, and urgent target vessel revascularization at 30 days. High-risk features were present in 21% of the patients. In patients without high-risk features after stent placement, abciximab reduced the primary endpoint from 9.0% to 3.9% (P <.001) compared with 16.2% to 8.6% (P =.046) in patients in whom high-risk features were present. There was no statistical evidence of interaction between abciximab treatment and the presence or absence of high-risk features. CONCLUSION: Glycoprotein IIb-IIIa antagonism with abciximab is equally effective in prevention of a composite of ischemic events in patients with and without high-risk features after stent placement. However, patients in whom high-risk features are present after stent placement are at increased risk of ischemic cardiac events even with abciximab treatment.

Abciximab↗
PubMed2002

Prognostic significance of creatine kinase-MB elevation after percutaneous coronary intervention in patients with chronic renal dysfunction.

BACKGROUND: Multiple studies have demonstrated a relationship between creatine kinase-MB (CK-MB) elevation after percutaneous coronary intervention (PCI) and increased late mortality within the general population. Because CK-MB is frequently elevated in renal disease even in the absence of myocardial injury, the clinical significance of CK-MB elevation after PCI in patients with renal insufficiency has been questioned. METHODS: We sought to examine the association between elevated CK-MB after PCI and late mortality in 190 consecutive patients with chronic renal insufficiency (serum creatinine > or =2.0 mg/dL) undergoing PCI at the Cleveland Clinic between January 1997 and March 2000. Of the total group, 20 patients undergoing PCI for acute myocardial infarction, cardiogenic shock, or both were excluded. Follow-up was 99.4% complete at a mean duration of 24.8 +/- 11.2 months (range 5-43 months). RESULTS: CK-MB elevation above the upper limit of normal after intervention was detected in 33 patients (19.4%). Baseline characteristics were not significantly different between the CK-MB elevation group and the normal CK-MB group. Late mortality, however, was significantly higher among patients with postprocedural CK-MB elevation (36.4% vs 17.5%, P =.017). Cox proportional hazard model revealed CK-MB elevation as an independent predictor of late mortality (hazard ratio 2.44, 95% CI 1.14-5.24, P =.02), in addition to New York Heart Association class (hazard ratio 1.35, 95% CI 1.05-1.73, P =.02). CONCLUSIONS: This analysis of patients with chronic renal insufficiency undergoing PCI suggests that postprocedural CK-MB elevation is an independent predictor of late mortality even in the presence of renal dysfunction.

Aged↗
PubMed2002

Bivalirudin with planned or provisional abciximab versus low-dose heparin and abciximab during percutaneous coronary revascularization: results of the Comparison of Abciximab Complications with Hirulog for Ischemic Events Trial (CACHET).

BACKGROUND: The direct thrombin inhibitor bivalirudin has previously been associated with better efficacy and lower hemorrhage risk than heparin during balloon angioplasty. This agent has not yet been tested with stenting or in combination with platelet glycoprotein IIb/IIIa antagonists. METHODS AND RESULTS: In a pilot trial, 268 patients who underwent coronary intervention were randomized in 3 sequential phases to treatment with bivalirudin (with or without abciximab) or the control regimen of low-dose weight-adjusted heparin with abciximab. Patients in the bivalirudin arms received bivalirudin (1.0 mg/kg bolus, infusion of 2.5 mg/kg/h for 4 hours) plus abciximab in phase A, bivalirudin (0.5 mg/kg bolus, infusion of 1.75 mg/kg/h for the procedure duration) plus provisional ("rescue") abciximab in phase B, or bivalirudin (0.75 mg/kg bolus, infusion of 1.75 mg/kg/h for the procedure duration) plus provisional abciximab in phase C. Abciximab was necessitated on a provisional basis in 24% of the patients in the bivalirudin arms of phases B and C. A composite clinical endpoint of death, myocardial infarction, repeat revascularization, or major bleeding by 7 days occurred in 3.3%, 5.9%, 0, and 10.6% of the patients in the bivalirudin phase A, bivalirudin phase B, bivalirudin phase C, and heparin plus planned abciximab arms, respectively (P =.018 for the pooled bivalirudin groups versus the heparin group). CONCLUSION: Bivalirudin with planned or provisional abciximab may be at least as safe and effective as low-dose heparin plus abciximab during percutaneous coronary intervention.

Abciximab↗
PubMed2002

Predicting outcome after thrombolysis in acute myocardial infarction according to ST-segment resolution at 90 minutes: a substudy of the GUSTO-III trial. Global Use of Strategies To Open occluded coronary arteries.

BACKGROUND: Resolution of ST-segment elevation after thrombolysis for acute myocardial infarction has been shown to have prognostic significance 3 hours (180 minutes) after the initiation of therapy. Whether prognostically useful information can be achieved as early as 90 minutes after thrombolysis is unknown. METHODS: An electrocardiographic substudy of 2352 patients from the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial was undertaken to compare outcomes according to ST-segment resolution at 90 minutes versus 180 minutes after administration of thrombolytic therapy. RESULTS: Of 2352 patients in the substudy, 2241 had a baseline and 90-minute electrocardiogram, and 2218 had a baseline and 180-minute ECG. Complete ST-segment resolution occurred in 44.2% of patients at 90 minutes and 56.5% of patients at 180 minutes. ST-segment resolution at both 90 and 180 minutes was associated with lower 30-day and 1-year mortality. Multivariate analysis revealed ST-segment resolution at 90 minutes to be an equally strong predictor of 30-day mortality as resolution at 180 minutes. Patients who were at particularly high risk for mortality were those aged >70 years, those who presented with Killip class >1, and those with anterior infarctions. CONCLUSIONS: The presence of ST-segment resolution on standard 12-lead electrocardiographic monitoring 90 minutes after thrombolysis is a useful independent predictor of mortality at 30 days and 1 year. The potential for obtaining prognostic results as early as 90 minutes after thrombolysis sets a new precedent for optimum electrocardiographic monitoring times in these patients.

Aged↗
PubMed2002

Promise of combined low-molecular-weight heparin and platelet glycoprotein IIb/IIIa inhibition: results from Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network B (PARAGON B).

BACKGROUND: Low-molecular-weight heparin (LMWH) has a more predictable anticoagulant effect than unfractionated heparin (UFH), is easier to administer, and does not require monitoring. Minimal data are available on LMWH combined with platelet glycoprotein (GP) IIb/IIIa inhibitors. METHODS: In the Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B (PARAGON B) trial, patients with an acute coronary syndrome were randomized to receive the IIb/IIIa inhibitor lamifiban or a placebo. To rigorously explore the potential benefits of LWMH and GP IIb/IIIa inhibition, we analyzed the rates of ischemic complications and safety outcomes in PARAGON B. RESULTS: Approximately one fifth of the patients received LMWH (805 vs 4395 UFH). For the overall cohort, the incidence of death/myocardial infarction (MI)/severe recurrent ischemia (SRI) was 12.2%, and this composite end point was numerically lowest in the lamifiban with LMWH group (10.2%). Similarly, the incidence of death/MI was 11.0% for the entire cohort and lowest in the lamifiban and LMWH group (9.0%). The lower event rate for patients taking LMWH in the lamifiban group was sustained at 6 months, with a lower revascularization rate (51.5% vs 42.8%) and a lower composite of death/MI (13.8% vs 11.9%). Bleeding was comparable in the 2 heparin groups (1.4% with UFH vs 0.9% with LMWH). The propensity adjusted odds ratio for 30-day revascularization was significantly lower with LMWH (odds ratio 0.67, 95% CI 0.57-0.79, P <.001). There were no significant differences in death/MI/SRI at 30 days (P =.465), death/MI at 30 days (P =.264), and stroke at 30 days with the type of heparin use (P =.201) after propensity risk adjustment. CONCLUSIONS: In the PARAGON B trial, use of LMWH in conjunction with a GP IIb/IIIa inhibitor was safe and associated with a lower revascularization rate. These findings support the rationale and promise for combining GP IIb/IIIa blockers and LMWH for future management of acute coronary syndrome.

Acetates↗
PubMed2002

Characteristics, treatment and outcome of patients with non-ST-elevation acute coronary syndromes and multivessel coronary artery disease: observations from PURSUIT (platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrelin therapy).

BACKGROUND: The 6-month clinical outcome of patients with multivessel disease enrolled in PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) is described. Patients with complete angiography data were included; multivessel disease was stratified according to the treatment strategy applied early during hospitalization, i.e. medical treatment, percutaneous coronary intervention (PCI) (balloon), PCI (stent), or coronary artery bypass grafting (CABG). METHODS: Patients were divided into three groups according to the treatment strategy applied during the first 30 days of enrolment. Patients who did not undergo a percutaneous or surgical coronary intervention were classified as medically treated. Patients who underwent a PCI (prior to a possible CABG) were separated from those who underwent a CABG (prior to a possible PCI). The PCI group was further subdivided: patients receiving >/=1 coronary stents were separated from those in whom no stents were used. RESULTS: The mortality rate at 30 days was 6.7, 3.9, 2.4 and 4.8% for the medical treatment, PCI (balloon), PCI (stent) and CABG groups, respectively (p value = 0.002). Differences as observed at 30 days were still present at 6-month follow-up with 11.1, 5.8, 5.5 and 6.5% mortality event rates for the aforementioned groups (p value = 0.002). The 30-day myocardial infarction (MI) rate according to the opinion of the Clinical Events Committee was lower among medically than non-medically treated patients, with the highest event rate observed in the CABG group (27.7%). Approximately half of the MIs in the PCI and CABG subgroups occurred within 48 h after the procedure. CONCLUSIONS: The observed differences in clinical outcomes are explained by an imbalance in baseline characteristics and comorbid conditions between the analyzed groups of patients.

Acute Disease↗
PubMed2002

Genetic testing for coronary heart disease: the approaching frontier.

The prospect for genetic testing to better delineate the risk for coronary heart disease will become a reality in the next decade. Advances in this area will follow the accelerated trajectory in our ability to dissect the genetics of complex diseases including coronary heart disease. A brief overview of the present state of knowledge will follow the discussion of present approaches in discovering these genetic predispositions. The key issues that will likely shape the field in the near future will also be presented.

Arteriosclerosis↗
PubMed2002

Local delivery of nitric oxide from an eluting stent to inhibit neointimal thickening in a porcine coronary injury model.

To assess the effect of a NO-eluting stent on reducing neointimal thickening in a porcine coronary artery stent injury model, sodium nitroprusside (SNP), a NO donor, was incorporated into polyurethane (PU) polymer and coated onto metallic coil stents, and two types of stents with thin and thick barrier coatings were characterized. In vivo biological activity of the NO-eluting stents was assessed by measurement of coronary arterial cGMP levels in 32 pigs/64 arteries at days 1, 2, 7 and 14. Morphometric analyses were performed in 16 pigs to determine the effect of NO-eluting stents on neointimal hyperplasia 28 days following arterial injury. The SNP-coated stents released NO in a controlled manner for up to 4 weeks in the in vitro experiments and an increase in local tissue cGMP levels was demonstrated for up to 14 days. The neointimal area at 28 days was not diminished, however, by NO eluded from either stents of thin or thick barriers (control bare stent - 0.66 mm2, control PU stent - 0.68 mm2, SNP-PU thin coating stent - 0.78 mm2, SNP-PU thick coating stent - 0.85 mm2; all p=NS). In conclusion, the SNP-coated polymer stent exerted a local biological effect on the arterial wall, with sustained elevation of cGMP level. Although local delivery of NO from this device did not reduce neointimal hyperplasia in this porcine model, this polymer-coated stent might be a promising tool for administration of other agents that may modify the reparative tissue responses leading to restenosis.

Animals↗
PubMed2002

Recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) attenuates infarct size and myeloperoxidase activity in a canine model of ischemia-reperfusion.

The role of P-selectin in the process of reperfusion injury was evaluated using a recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in a canine coronary artery balloon occlusion model. rPSGL-Ig (1 mg/kg) or saline was given as an intravenous bolus 15 min before balloon deflation. Balloon occlusion time was 90 min followed by either 120 min or 7 days reperfusion. Infarct size was significantly reduced in the treatment group when expressed either as percentage of the area at risk or as absolute infarct size. Histological analysis showed that extensive myocardial injury and neutrophil infiltration were reduced by rPSGL-Ig. Myeloperoxidase activity (MPO) was significantly reduced in the risk area in the rPSGL-Ig group. Left ventricular ejection fraction was significantly less impaired during the first 24 h after reperfusion in the rPSGL-Ig group, although there was no difference by 7-day follow-up. Thus, administration of rPSGL-Ig decreases myocardial injury and inflammatory response for at least 7 days after reperfusion of ischemic myocardium.

Animals↗
PubMed2001

Systematic adjudication of myocardial infarction end-points in an international clinical trial.

BACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. RESULTS: The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. CONCLUSIONS: End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates.

Journal Article↗
PubMed2001

Disagreements between central clinical events committee and site investigator assessments of myocardial infarction endpoints in an international clinical trial: review of the PURSUIT study.

BACKGROUND: Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and those adjudicated by a central clinical events committee (CEC) to determine the reasons for differences in event rates. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. The primary end-point was death or post-enrolment MI at 30 days as assessed by the CEC; this end-point was also constructed using site-reported events. The CEC identified suspected MIs by systematic review of clinical, cardiac enzyme, and electrocardiographic data. RESULTS: The CEC identified 5005 (46%) suspected events, of which 1415 (28%) were adjudicated as MI. The site investigator and CEC assessments of whether a MI had occurred disagreed in 983 (20%) of the 5005 patients with suspected MI, mostly reflecting site misclassification of post-enrolment MIs (as enrolment MIs) or underreported periprocedural MIs. Patients for whom the CEC and site investigator agreed that no end-point MI had occurred had the lowest mortality at 30 days and between 30 days and 6 months, and those with agreement that a MI had occurred had the highest mortality. CONCLUSION: CEC adjudication provides a standard, systematic, independent, and unbiased assessment of end-points, particularly for trials that span geographic regions and clinical practice settings. Understanding the review process and reasons for disagreement between CEC and site investigator assessments of MI is important to design future trials and interpret event rates between trials.

Journal Article↗
PubMed2001

Debate: PCI or CABG for multivessel disease? Viewpoint: No clear winner in an unfair fight.

The Arterial Revascularization Therapy Study (ARTS) and the Stent or Surgery (SoS) trial each randomized patients with multivessel disease to either stenting or bypass surgery. The ARTS showed no difference in mortality between the two strategies, other than in diabetic patients, who fared better with surgery. The SoS trial demonstrated increased mortality in the stent arm, a difference that was not attributable to diabetes. Both trials found that the rates of repeat revascularization were lower with surgery, although the rate with stenting was much lower than had been seen in previous trials of angioplasty. Use of antiplatelet therapy such as intravenous glycoprotein IIb/IIIa inhibitors, especially with their pronounced effects in diabetics and in those with multivessel disease, could potentially equalize the playing field or perhaps even tip the balance in favor of percutaneous intervention.

Journal Article↗
PubMedDate not supplied

Autologous cell transplantation for the treatment of damaged myocardium.

Autologous cell transplantation for the treatment of damaged myocardium after myocardial infarction is becoming an increasingly promising strategy. This form of treatment can be divided into 2 treatment strategies: The first uses differentiated cell types to replace the scarred tissue with living cells, while the second strategy uses stem cells in an attempt to regenerate myocardium. Over the past decade, multiple cell types have been used in animal studies, and clinical trials to determine the safety of injecting and engrafting skeletal myoblasts into damaged myocardium are presently being conducted. Animals studies focused on using stem cells to regenerate damaged myocardium have shown a naturally occurring reparative process that consists of up-regulation of progenitor cell release from the bone marrow after myocardial infarction, homing of these cells to the injured tissue, and differentiation of these progenitor cells into vascular cells and cardiac myocytes within the infarcted tissue. Unfortunately, this process occurs with great infrequency. Strategies to regenerate myocardium with stem cells either extract stem cells from the bone marrow and inject these cells into the damaged area or they attempt to increase the efficiency of the natural reparative process by increasing the mobilization of bone marrow-derived stem cells after myocardial infarction. This review summarizes the field of cell transplantation over the past decade, discusses areas of controversy, and proposes an outline of advancements that need to be made in both the clinical and scientific arenas for autologous cell transplantation to fully reach its clinical potential.

Animals↗
PubMedDate not supplied

Pharmacogenomics in cardiovascular diseases.

Considerable heterogeneity exists in the way individuals respond to medications, in terms of both efficacy and safety. Inherited differences in the absorption, metabolism, excretion, and target for drug therapy have important effects on drug efficacy and safety. Pharmacogenomics aims to discover new therapeutic targets and understand genetic polymorphisms that determine the safety and efficacy of medications. The goal of pharmaco-genomics is customization of drug therapy with administration of a medication in an optimum dose that will be safe and effective with reduction in morbidity and mortality.

Cardiovascular Diseases↗
PubMedDate not supplied

The role of low-molecular-weight heparin in cardiovascular diseases.

Unfractionated heparin continues to have important limitations in clinical practice. It has an inconsistent anticoagulant effect, needs frequent monitoring, and is inactivated by several plasma proteins. Low-molecular-weight heparins have a more predictable anticoagulant effect than unfractionated heparin, are easier to administer, and may not require monitoring. The anticoagulation effect of low-molecular-weight heparins is caused by a combination of inhibition of thrombin generation and inhibition of thrombin activity. Low-molecular-weight heparins have now been evaluated for a number of cardiovascular conditions and have been found to be safe and effective. We review and summarize the existing data regarding the use of low-molecular-weight heparins in cardiovascular diseases, including venous thromboembolism, percutaneous coronary interventions, and acute coronary syndromes such as ST-segment elevation myocardial infarction.

Angina, Unstable↗