Showing papers by "Eric J. Topol published in 2000"
TL;DR: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors and these factors should be considered in the clinical decision-making process.
Abstract: BACKGROUND: Appropriate treatment policies should include an accurate
estimate of a patient's baseline risk. Risk modeling to date has been
underutilized in patients with acute coronary syndromes without persistent
ST-segment elevation. METHODS AND RESULTS: We analyzed the relation
between baseline characteristics and the 30-day incidence of death and the
composite of death or myocardial (re)infarction in 9461 patients with
acute coronary syndromes without persistent ST-segment elevation enrolled
in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina:
Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables
examined included demographics, history, hemodynamic condition, and
symptom duration. Risk models were created with multivariable logistic
regression and validated by bootstrapping techniques. There was a 3.6%
mortality rate and 11.4% infarction rate by 30 days. More than 20
significant predictors for mortality and for the composite end point were
identified. The most important baseline determinants of death were age
(adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure
(chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure
(chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality
were generally also predictive of death or myocardial (re)infarction.
Differences were observed, however, in the relative prognostic importance
of predictive variables for mortality alone or the composite end point;
for example, sex was a more important determinant of the composite end
point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the
prediction of the composite end point was less than that of mortality
(C-index 0.67 versus 0.81). CONCLUSIONS: The occurrence of adverse events
after presentation with acute coronary syndromes is affected by multiple
factors. These factors should be considered in the clinical
decision-making process.
948 citations
TL;DR: The purpose of this article is to present the case for a disturbingly and unexpectedly high rate of arterial embolization in certain atherosclerotic conditions and to review the promise of newer therapeutics or devices to reduce the risk or ameliorate the sequelae of emblization.
Abstract: It is uncommon in medicine for emerging data to completely transform a field, particularly in such a common disease state as atherosclerotic vascular disease. New evidence from multiple fronts has underscored the frequency and prognostic importance of atherosclerotic embolization in the microvasculature. Until recently, we have had limited access to diagnose microvascular obstruction in living patients. With the availability of imaging technology that includes magnetic resonance, myocardial contrast echocardiography, and transcerebral or transcranial Doppler (TCD), microvascular obstruction has been documented in a far greater proportion of patients than ever conceived. The linkage between microvascular obstruction and unfavorable long-term clinical prognosis has been established in many series. Furthermore, therapeutics shown to reduce microvascular obstruction have improved clinical outcomes. The purpose of this article is to present the case for a disturbingly and unexpectedly high rate of arterial embolization in certain atherosclerotic conditions and to review the promise of newer therapeutics or devices to reduce the risk or ameliorate the sequelae of embolization.
Acute myocardial infarction (MI) has been accepted to be related primarily to a fissured, eroded, or ruptured plaque.1 2 3 4 5 This event leads to exposure of subendothelial matrix, with attendant platelet aggregation, thrombus, and occlusion of a major epicardial vessel. In a continuum, unstable angina and non–ST-segment-elevation MI also are indexed to a breech of the arterial wall, but the resultant thrombus is usually mural, not occlusive. Embolization of plaque contents of platelet-thrombus into the microvasculature has been reported in some patients with these acute coronary syndromes, but it has been generally believed to be uncommon.1 2 6 7 In some cases of sudden death, the process of embolization has been speculated to play an important role. It is nevertheless surprising that systematic pathological studies of the microvasculature of the postmortem heart infarct territory have …
752 citations
TL;DR: Compared with historical control subjects, patients who undergo thrombolysis within 6 hours of infarction onset may have a reduced risk of later VSD, and patients with VSDs selected for surgical repair had better outcomes than patients treated medically.
Abstract: Background —Ventricular septal defect (VSD) complicating acute myocardial infarction has been studied primarily in small, prethrombolytic-era trials. Our goal was to determine clinical predictors and angiographic and clinical outcomes of this complication in the thrombolytic era. Methods and Results —We compared enrollment characteristics, angiographic patterns, and outcomes (30-day and 1-year mortality) of patients enrolled in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial with and without a confirmed diagnosis of VSD. Univariable and multivariable analyses were used to assess relations between enrollment factors and the development of VSD. In all, 84 of the 41 021 patients (0.2%) developed VSD, a smaller percentage than reported in the prethrombolytic era. The median time from symptom onset to VSD diagnosis was 1 day. Enrollment factors most associated with this complication were advanced age, anterior infarction, female sex, and no previous smoking. The infarct artery was more often the left anterior descending and more likely to be totally occluded in patients who developed VSD. Mortality at 30 days was higher in patients with VSDs than in those without this complication (73.8% versus 6.8%, P Conclusions —Compared with historical control subjects, patients who undergo thrombolysis within 6 hours of infarction onset may have a reduced risk of later VSD. If patients develop this mechanical complication, however, it typically occurs sooner than described in the prethrombolytic era. Despite improvements in medical therapy and percutaneous and surgical techniques, mortality with this complication remains extremely high.
619 citations
TL;DR: Abciximab therapy should be strongly considered in diabetic patients undergoing PCI to improve their survival and is noteworthy in those diabetic patients who are also hypertensive and obese and in diabetics undergoing multivessel intervention.
335 citations
TL;DR: Current data indicate that intravenous Gp IIb/IIIa inhibitor therapy merits a prominent role in the initial management of patients with ACSs, and biological differences exist among these agents, but as of yet no head-to-head comparisons have been made of their clinical efficacy.
Abstract: ContextThe central role of platelet-rich thrombus in the pathogenesis of acute
coronary syndromes (ACSs) is well-known. Glycoprotein IIb/IIIa (Gp IIb/IIIa)
receptor antagonists are potent inhibitors of platelet function that may be
expected to affect favorably the natural history of ACSs.ObjectiveTo define the optimal role of Gp IIb/IIIa inhibitors in treatment strategies
for ACSs.Data SourcesA MEDLINE search was performed to identify all English-language articles
regarding use of Gp IIb/IIIa inhibitors in ACSs published between 1966 and
June 2000. In addition, relevant abstracts from the annual meetings of the
American Heart Association, American College of Cardiology, and the European
Society of Cardiology were reviewed.Study SelectionOnly studies of 500 or more patients were included. Of 15 studies identified,
10 randomized, placebo-controlled, double-blind trials of Gp IIb/IIIa inhibitors
in ACSs were selected for review.Data ExtractionData quality was determined by publication in the peer-reviewed literature
or presentation at an official cardiology society–sponsored meeting,
as well as by verification with the primary author.Data SynthesisThree members of this class of drugs are available for intravenous use.
Abciximab, eptifibatide, and tirofiban hydrochloride, each have data demonstrating
their value in improving the outcomes of patients presenting with ACSs. Current
evidence supports use of these drugs in both conservative and invasive treatment
strategies. Glycoprotein IIb/IIIa–blocking therapy is safe, and with
proper precautions, bleeding risks can be minimized. Biological differences
exist among these agents, but as of yet, no head-to-head comparisons have
been made of their clinical efficacy. Unlike intravenous Gp IIb/IIIa inhibitors,
available data regarding any role of oral Gp IIb/IIIa inhibitors are not favorable.ConclusionCurrent data indicate that intravenous Gp IIb/IIIa inhibitor therapy
merits a prominent role in the initial management of patients with ACSs.
261 citations
Journal Article•
TL;DR: Sibrafiban showed no additional benefit over aspirin for secondary prevention of major ischaemic events after an acute coronary syndrome, and was associated with more dose-related bleeding.
237 citations
TL;DR: Worsening heart failure, hypotension, third-degree heart block, and ventricular fibrillation were independent predictors of new-onset AF and independently portends a worse prognosis.
212 citations
TL;DR: In this article, the authors identified independent baseline predictors of insignificant coronary artery disease (mild or no CAD) and used them to develop a simple predictive nomogram of the probability of insignificant CAD for use at a hospital presentation, which can be used to determine indications for glycoprotein IIb/IIIa blockade.
Abstract: BACKGROUND: A proportion of patients who present with suspected acute
coronary syndrome (ACS) are found to have insignificant coronary artery
disease (CAD) during coronary angiography, but these patients have not
been well characterized METHODS AND RESULTS: Of the 5767 patients with
non-ST-segment elevation ACS who were enrolled in the Platelet
Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using
Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent
in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6%
had mild CAD (any stenosis >0% to
198 citations
TL;DR: Early PCI facilitated by a combination of abciximab and reduced-dose reteplase was safe and effective and has several advantages for acute MI patients, which should be confirmed in a dedicated, randomized trial.
198 citations
TL;DR: The statistically non-significant trend toward improved outcomes with hirudin was similar among patients with and without diabetes, with a greater point estimate for the absolute difference in patients with diabetes.
Abstract: Aims We examined the characteristics, outcomes, and effects of hirudin vs heparin treatment of diabetic patients across the spectrum of acute coronary syndromes.
Methods and Results We studied the 12142 patients enrolled in the randomized GUSTO-IIb study. Diabetic patients (n=2175) were older, more often female, more often had prior cardiovascular disease, hypertension, and hyperlipidaemia, and less often were current smokers. Diabetic patients had a higher overall incidence of death or (re)infarction at 30 days (13·1% vs 8·5%, P =0·0001), whether they presented with ST-segment elevation (13·9% vs 9·9%, P =0·0017) or not (12·8% vs 7·8%, P =0·0001), and at 6 months (18·8% vs 11·4%, P =0·0001). Among diabetic patients, hirudin was associated with a tendency toward a lower risk of death or (re)infarction at 30 days (12·2% vs 13·9% with heparin) and 6 months (17·8% vs 20·2%). Diabetic patients had more major bleeding, stroke, heart failure, shock, atrioventricular block, and atrial arrhythmias, but no increased risk for ocular bleeding.
Conclusions Diabetic patients with acute coronary syndromes had worse 30-day and 6-month outcomes, particularly those without ST-segment elevation. The statistically non-significant trend toward improved outcomes with hirudin was similar among patients with and without diabetes, with a greater point estimate for the absolute difference in patients with diabetes.
185 citations
TL;DR: Blockage of the platelet glycoprotein IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute isChemic syndromes.
TL;DR: Algorithms are presented that predict the occurrence of cardiogenic shock in both ST-segment-elevation myocardial infarction and unstable angina or non-ST-e Elevation my Cardiogenic Infarction, and that predict its mortality in patients with ST-SEgment-Elevation acute myocardials.
TL;DR: Clinicians can estimate the likelihood of survival from factors easily measured during admission, although many risk factors clearly relate to age, left ventricular dysfunction, or clinical instability, black race is an unexplained risk factor requiring further examination.
Abstract: Background —When a patient survives thrombolysis for acute myocardial infarction, little information from large studies exists from which to estimate prognosis during follow-up visits Methods and Results —Baseline, in-hospital, and later survival data were collected from 41 021 patients enrolled in Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries, a randomized trial of 4 thrombolytic-heparin regimens with standard aspirin and β-blockade Cox proportional hazards models were developed to predict 1-year survival in 30-day survivors (n=37 869) from baseline clinical and ECG factors and in-hospital factors; a combined model then was developed (C-index 0800) The model was simplified into a nomogram to predict individual outcomes (C-index 0754) Factors reflecting demographics (advanced age, lighter weight), larger infarctions (higher Killip class, lower blood pressure, faster heart rate, longer QRS duration), cardiac risk (smoking, hypertension, prior cerebrovascular disease), and arrhythmia were important predictors of death between 30 days and 1 year Black race was associated with a substantial increase in risk after considering other factors Revascularization was associated with reduced risk between 30 days and 1 year Conclusions —When evaluating a patient who has survived acute infarction treated with thrombolysis, clinicians can estimate the likelihood of survival from factors easily measured during admission Although many risk factors clearly relate to age, left ventricular dysfunction, or clinical instability, black race is an unexplained risk factor requiring further examination
TL;DR: Hospitalization of patients with uncomplicated myocardial infarction beyond three days after thrombolysis is economically unattractive by conventional standards.
Abstract: Background Reducing the length of hospitalizations can reduce short-term costs, but there are few data on the long-term clinical and economic consequences of early discharge after uncomplicated myocardial infarction. Methods Using data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, we identified 22,361 patients with acute myocardial infarction who had an uncomplicated course for 72 hours after thrombolysis. Then, using a decision-analytic model, we examined the cost effectiveness of an additional day of hospitalization in this group. We defined incremental survival attributable to another day of monitored hospitalization, on the basis of the rate of resuscitation after cardiac arrest between 72 and 96 hours. Lifetime survival curves for each group in the decision-analytic model were estimated from one-year survival data from GUSTO-1. Results Of the patients with an uncomplicated course within 72 hours after thrombolysis, 16 had...
TL;DR: A scoring system accurately predicts the risk of shock after thrombolytic therapy for acute myocardial infarction based primarily on the patient's age and physical examination on presentation.
TL;DR: Treatment with clopidogrel results in a significant decrease in the need for rehospitalization for ischemic events or bleeding compared with aspirin, and this meaningful end point tracks well with other, more traditional measures of outcome and has incremental value beyond such end points.
TL;DR: Patients with shock treated with eptifibatide had significantly reduced adjusted odds of death, suggesting a salutary effect of antiplatelet therapy on shock, which warrants verification in specifically designed studies.
TL;DR: This pooled analysis demonstrated no gender difference in protection from major adverse outcomes with GP IIb/IIIa inhibition with abciximab, and major bleeding in women was similar with and without abcximab.
TL;DR: Based on the results observed in the US PURSUIT patients, the routine addition of eptifibatide to standard care for non-ST-elevation acute coronary syndrome patients is economically attractive by conventional standards.
Abstract: Background —In the PURSUIT trial, eptifibatide significantly reduced the 30-day incidence of death and myocardial infarction relative to placebo in 9461 patients with an acute coronary syndrome (unstable angina or non–Q-wave myocardial infarction).
Methods and Results —We conducted a 2-part prospective economic substudy of the 3522 US patients enrolled in PURSUIT: (1) an empirical intention-to-treat comparison of medical costs (hospital plus physician) up to 6 months after hospitalization and (2) a lifetime cost-effectiveness analysis. The base-case cost-effectiveness ratio was expressed as the 1996 US dollars required to add 1 life-year with eptifibatide therapy. The 2 treatment arms had equivalent resource consumption and medical costs (exclusive of the cost of the eptifibatide regimen) during the index (enrollment) hospitalization ( P =0.78) and up to 6 months afterward ( P =0.60). The average wholesale price of the eptifibatide regimen was $1217, but a typical hospital discounted price was $1014. The estimated life expectancy from randomization in the US patients was 15.96 years for eptifibatide and 15.85 years for placebo, an incremental difference of 0.111. The incremental cost-effectiveness ratio for eptifibatide therapy in US PURSUIT patients was $16 491 per year of life saved. This result was robust through a wide range of sensitivity analyses. The cost-utility ratio for eptifibatide (using time trade-off defined utilities) was $19 693 per added quality-adjusted life-year.
Conclusions —Based on the results observed in the US PURSUIT patients, the routine addition of eptifibatide to standard care for non–ST-elevation acute coronary syndrome patients is economically attractive by conventional standards.
TL;DR: The data show that elevation of CK- MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal.
Abstract: CONTEXT: Controversy surrounds the diagnostic and prognostic importance of
slightly elevated cardiac markers in patients with acute coronary
syndromes without ST-segment elevation. OBJECTIVES: To investigate the
relationship between peak creatine kinase (CK)-MB level and outcome and to
determine whether a threshold CK-MB level exists below which risk is not
increased. DESIGN AND SETTING: Retrospective observational analysis of
data from the international Platelet Glycoprotein IIb/IIIa in Unstable
Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial,
conducted from November 1995 to January 1997. PATIENTS: A total of 8250
patients with acute coronary syndromes without ST-segment elevation who
had at least 1 CK-MB sample collected during their index hospitalization.
MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by
category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5,
>5-10, or >10 times the upper limit of normal). Multivariable logistic
regression was used to determine the independent prognostic significance
of peak CK-MB level after adjustment for baseline predictors of 30-day and
6-month mortality. RESULTS: Mortality at 30 days and 6 months increased
from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB
levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to
5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and
11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed
peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality
(P<.001 for both). CONCLUSIONS: Our data show that elevation of CK-MB
level is strongly related to mortality in patients with acute coronary
syndromes without ST-segment elevation, and that the increased risk begins
with CK-MB levels just above normal. In the appropriate clinical context,
even minor CK-MB elevations should be considered indicative of myocardial
infarction.
TL;DR: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively and this association disappeared after adjustment for propensity for early PCI.
Abstract: BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the
composite end point of death or myocardial infarction (MI) in patients
with acute coronary syndromes. There is uncertainty about whether this
effect is confined to patients who have percutaneous coronary
interventions (PCIs) and whether PCIs further prevent death or MI in
patients already treated with GP IIb/IIIa antagonists. METHODS AND
RESULTS: PURSUIT patients were treated with the GP IIb/IIIa antagonist
eptifibatide or placebo; PCIs were performed according to physician
practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days.
Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo
patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI
preceded early PCI. In patients censored for PCI across the 30-day period,
there was a significant reduction in the primary composite end point in
eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in
patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients
who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI
propensity, there was no evidence that eptifibatide treatment effect
differed between patients with or without early PCI (P for
interaction=0.634). PCI was not associated with a reduction of the primary
composite end point but was associated with a reduced (nonspecified)
composite of death or Q-wave MI. This association disappeared after
adjustment for propensity for early PCI. CONCLUSIONS: Eptifibatide reduced
the composite rates of death or MI in PCI patients and those managed
conservatively.
TL;DR: It is demonstrated that pseudothrombocytopenia is a benign laboratory condition that does not increase bleeding, stroke, transfusion requirements or the need for repeat revascularization.
TL;DR: The striking qualitative and quantitative lack of perihematomal edema observed in the thrombolysis-related ICHs compared with the SICHs provides the first substantial, although indirect, human evidence that intrahematomal blood clotting is a plausible pathogenetic factor in hyperacute perielectrical edema formation.
Abstract: Background and Purpose—Intracerebral hemorrhage (ICH) is a highly morbid disease process. Perihematomal edema is reported to contribute to clinical deterioration and death. Recent experimental observations indicate that clotting of the intrahematomal blood is the essential prerequisite for hyperacute perihematomal edema formation rather than blood-brain barrier disruption. Methods—We compared a series of patients with spontaneous ICH (SICH) to a series of patients with thrombolysis-related ICH (TICH). All patients were imaged within 3 hours of clinical onset. We reviewed relevant neuroimaging features, emphasizing and quantifying perihematomal edema. We then analyzed clinical and radiological differences between the 2 ICH types and determined whether these factors were associated with perihematomal edema. Results—TICHs contained visible perihematomal edema less than half as often as SICHs (31% versus 69%, P<0.001) and had both lower absolute edema volumes (0 cc [25th, 75th percentiles: 0, 6] versus 6 cc [...
TL;DR: Femoral closure devices have a similar overall risk profile as manual compression, even in patients treated with glycoprotein IIb/IIIa platelet inhibition, although certain rare complications such as retroperitoneal hemorrhage and severe access-site infection may be more common with the use of these devices.
Abstract: We compared in-hospital femoral complications of Angio-Seal, Perclose, and manual compression in consecutive patients who underwent percutaneous coronary interventions in the era of glycoprotein IIb/IIIa platelet inhibition. Femoral closure devices have a similar overall risk profile as manual compression, even in patients treated with glycoprotein IIb/IIIa platelet inhibition, although certain rare complications such as retroperitoneal hemorrhage and severe access-site infection may be more common with the use of these devices.
TL;DR: Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.
TL;DR: Primary angioplasty was similarly successful in diabetic and nondiabetics and appeared to be more effective than thrombolytic therapy among diabetics with acute infarction.
TL;DR: Thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention was more frequent in older, lighter-weight patients, those with lower baseline platelet counts, and in those patients who were enrolled into the EPIC trial.
TL;DR: The combination of stenting and abciximab during percutaneous coronary interventions for patients with angiographically complex lesions confers additive long-term benefit with respect to death, myocardial infarction, and target vessel revascularization.
Abstract: Background—Previous trials testing stents compared with balloon angioplasty excluded patients with complex lesions and did not assess the effect of adjunctive platelet IIb/IIIa inhibition. This analysis sought to assess the effect of stenting and abciximab specifically for patients with complex lesions. Methods and Results—Patients with complex lesions (long, tandem, severely calcified, restenotic, thrombotic, or ostial; total occlusions; bifurcations; saphenous vein grafts; and multivessel interventions) from the Evaluation of PTCA to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials were included in the analysis. The 1-year combined death or myocardial infarction rates in the 4 treatment groups were as follows: balloon angioplasty/placebo, 14.2%; stent/placebo, 15.8%; balloon angioplasty/abciximab, 7.6%; and stent/abciximab, 8.0% (P<0.001). Death rates were 3.2%, 3.1%, 2.1%, and 0.5%, respectively (P=...
TL;DR: The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world.
Abstract: Background—A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States Methods and Results—Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase–MB elevation were eligible for enrollment Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours
TL;DR: The impaired ventricular performance at the noninfarct areas and metabolic derangements during the acute phase of MI may account for the adverse outcome and therapeutic approaches should consider correcting these abnormalities to afford greater survival benefit for this subset of high-risk patients.