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Biomedical subjects

Eric R Bates

Publications and source records attributed to Eric R Bates.

At least 37 records · Page 2Linked to original sources
PubMed2004

Association of race with complications and prognosis following acute coronary syndromes.

The baseline characteristics, complications, and survival of 489 black and 6,890 non-black patients with acute coronary syndromes were studied. Important racial differences were observed in demographic features, atherosclerosis risk factors, and treatment strategies; however, despite these differences, no independent difference was observed in clinical outcomes according to race. The 1-year mortality rate was 2.9% for black patients and 2.5% for non-black patients (p = 0.93).

Acute Disease↗
PubMed2004

Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance.

BACKGROUND: Interindividual variability of platelet inhibition after aspirin or clopidogrel administration has been described. Additionally, aspirin resistance and clopidogrel resistance occur in some individuals. Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. METHODS AND RESULTS: Platelet aggregation was measured before and after clopidogrel treatment in 32 patients undergoing coronary artery stent implantation and in 35 healthy volunteers. The erythromycin breath test was used to measure CYP3A4 activity in vivo in 25 of the healthy volunteers. Individual platelet aggregation was studied in 10 healthy volunteers after the coadministration of clopidogrel and rifampin (a CYP3A4 inducer). Clopidogrel nonresponders, low responders, and responders were defined by a relative inhibition of adenosine diphosphate (20 micromol/L)-induced platelet aggregation of <10%, 10% to 29%, and > or =30%, respectively. Among patients, 22% were clopidogrel nonresponders, 32% were low responders, and 47% were responders. Among volunteers, 16% were nonresponders, 12% were low responders, and 72% were responders. Percent platelet aggregation after clopidogrel inversely correlated with CYP3A4 activity (r=-0.6, P=0.003). Improved platelet inhibition in volunteers resistant to clopidogrel was observed with the coadministration of clopidogrel and rifampin. CONCLUSIONS: Clopidogrel administration results in interindividual variability in platelet inhibition, which correlates with CYP3A4 metabolic activity. Measurement of antiplatelet drug efficacy with a point-of-care device and alternative antithrombotic strategies for aspirin or clopidogrel nonresponders and low responders could reduce the incidence of thrombotic events that continue to occur despite oral antiplatelet therapy.

Clopidogrel↗
PubMed2004

Current role of antithrombotic agents in the treatment of acute coronary syndromes.

Acute coronary syndromes (ACS) refer to a spectrum of myocardial ischemic disorders characterized by atherothrombotic plaque disruption. The management of ACS presents a challenge to the cardiologist because treatment strategies continue to evolve. Thrombin plays a pivotal role in thrombus formation, converting fibrinogen to fibrin, activating platelets, and recruiting additional platelets into the platelet-rich thrombus. In addition to unfractionated heparin (UFH), newer antithrombotic agents are now available and have significantly changed contemporary clinical practice. Low-molecular-weight heparins (LMWHs) has been shown to be superior to UFH in several trials. Direct thrombin inhibitors (DTIs) have been shown to be effective in patients undergoing elective coronary interventions and are being evaluated in patients with ACS. We review two classes of antithrombotic drugs, the LMWHs and the DTIs and discuss their current roles in the management of patients with ACS.

Aged↗
PubMed2004

Bivalirudin: an anticoagulant option for percutaneous coronary intervention.

Coronary artery thrombosis is usually triggered by platelet-rich thrombus superimposed on a spontaneously or mechanically disrupted atherosclerotic plaque. Thrombin and platelets both play a role in this process. Unfractionated heparin and aspirin have served as cornerstones in the prevention and treatment of intracoronary thrombus, but unfractionated heparin has several limitations that necessitate the use of adjunctive therapies, such as glycoprotein IIb/IIIa receptor inhibitors and clopidogrel, in order to reduce the risk of ischemic events. These combination therapies, however, typically increase the risk for bleeding complications, as well as the cost and complexity of treatment. Bivalirudin (Angiomax, The Medicines Company), a thrombin-specific anticoagulant, does not share heparin's limitations. Bivalirudin appears to provide clinical advantages over unfractionated heparin therapy in acute coronary syndrome patients and those undergoing percutaneous coronary intervention, without increasing cost or complexity of treatment for most patients.

Acute Disease↗
PubMed2003

Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything?

The mortality benefit associated with primary percutaneous coronary intervention in ST-segment elevation myocardial infarction may be lost if door-to-balloon time is delayed by >1 hour as compared with fibrinolytic therapy door-to-needle time. Interventional cardiology laboratories endeavoring to achieve the benefits of primary percutaneous coronary intervention seen in randomized clinical trials should aim to match their short door-to-balloon times.

Angioplasty, Balloon, Coronary↗
PubMed2003

Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction.

BACKGROUND: We observed that the prodrug clopidogrel was less effective in inhibiting platelet aggregation with coadministration of atorvastatin during point-of-care platelet function testing. Because atorvastatin is metabolized by cytochrome P450 (CYP) 3A4, we hypothesized that clopidogrel might be activated by CYP3A4. METHODS AND RESULTS: Platelet aggregation was measured in 44 patients undergoing coronary artery stent implantation treated with clopidogrel or clopidogrel plus pravastatin or atorvastatin, and in 27 volunteers treated with clopidogrel and either erythromycin or troleandomycin, CYP3A4 inhibitors, or rifampin, a CYP3A4 inducer. Atorvastatin, but not pravastatin, attenuated the antiplatelet activity of clopidogrel in a dose-dependent manner. Percent platelet aggregation was 34+/-23, 58+/-15 (P=0.027), 74+/-10 (P=0.002), and 89+/-7 (P=0.001) in the presence of clopidogrel and 0, 10, 20, and 40 mg of atorvastatin, respectively. Erythromycin attenuated platelet aggregation inhibition (55+/-12 versus 42+/-12% platelet aggregation; P=0.002), as did troleandomycin (78+/-18 versus 45+/-18% platelet aggregation; P<0.0003), whereas rifampin enhanced platelet aggregation inhibition (33+/-18 versus 56+/-20% platelet aggregation, P=0.001). CONCLUSIONS: CYP3A4 activates clopidogrel. Atorvastatin, another CYP3A4 substrate, competitively inhibits this activation. Use of a statin not metabolized by CYP3A4 and point-of-care platelet function testing may be warranted in patients treated with clopidogrel.

Adolescent↗
PubMed2003

Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study.

BACKGROUND: In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). METHODS: The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia. RESULTS: A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively). CONCLUSIONS: The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.

Abciximab↗
PubMed2003

Direct thrombin inhibitors in cardiac disease.

Most acute coronary syndromes (ACS) are triggered by platelet-rich thrombus superimposed on disrupted atherosclerotic plaque. Thrombin and platelets both play a role in this process. Whereas unfractionated heparin and aspirin have served as cornerstones in the treatment of ACS, several limitations of heparin provide the impetus to seek out better anticoagulants. Direct thrombin inhibitors such as bivalirudin, hirudin, and argatroban offer several pharmacologic advantages over heparin. Additionally, bivalirudin also appears to provide clinical advantages over unfractionated heparin therapy in ACS patients and those undergoing percutaneous coronary intervention.

Arginine↗
PubMed2003

Reducing costs and improving outcomes of percutaneous coronary interventions.

OBJECTIVE: To describe cost reduction and quality improvement efforts in our percutaneous coronary intervention (PCI) program and how risk adjustment was used to assess the effects of these changes. STUDY DESIGN: Single center registry analysis. PATIENTS AND METHODS: Data were collected on 2158 PCIs performed between July 1, 1994, and June 30, 1997. Of these, 1126 PCIs reflected care provided after implementation of competitive bidding for catheterization lab supplies, and efforts to reduce the use of postprocedure heparin and to implement early arterial sheaths removal (postbidding period). Hospital costs were estimated using a microcost accounting method. In-hospital mortality rates during the 2 time periods were compared using standardized mortality ratio estimated with a previously validated risk adjustment model for in-hospital mortality. RESULTS: Compared with the prebidding period, the postbidding period was characterized by a significantly higher utilization of new technology (coronary stents and atherectomy devices 46% vs 25%; abciximab 19.1% vs 3.7, P<.01), and an overall increase in case complexity. Despite these changes, the average and median postbidding cost per case was dollars 1223 and dollars 1444 lower, respectively, than in the prebidding period. After adjustment for comorbidities, procedure variables, complications, and length of hospital stay, multivariate regression modeling identified the postbidding period as an independent predictor of lower hospital costs (P<.001) with an estimated adjusted cost savings of dollars 460. These cost savings were associated with trends toward a lower observed mortality rate, a higher predicted mortality rate, and a significantly lower standardized mortality ratio (SMR .71; 95% CI 0.48-0.9; P<.05). CONCLUSION: Despite an increase in case complexity and utilization of new technology, cost reductions can be achieved through competitive bidding for supplies and modifications of periprocedure care. Risk adjustment appears to be a valid tool for assessing the effectiveness of these efforts independently from changes in case mix.

Aged↗
PubMed2002

Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2).

OBJECTIVES: The purpose of this study was to examine treatment and outcomes in patients admitted to the hospital with acute myocardial infarction (AMI) complicated by congestive heart failure (CHF). BACKGROUND: Although cardiogenic shock complicating AMI has been studied extensively, the hospital course of patients presenting with CHF is less well established. METHODS: The Second National Registry of Myocardial Infarction (NRMI-2) was analyzed to determine hospital outcomes for patients with ST-elevation AMI admitted with CHF (Killip classes II or III). RESULTS: Of 190,518 patients with AMI, 36,303 (19.1%) had CHF on admission. Patients presenting with CHF were older (72.6 +/- 12.5 vs. 63.2 +/- 13.5 years), more often female (46.8% vs. 32.1%), had longer time to hospital presentation (2.80 +/- 2.6 vs. 2.50 +/- 2.4 h), and had higher prevalence of anterior/septal AMI (38.8% vs. 33.3%), diabetes (33.1% vs. 19.5%), and hypertension (54.6% vs. 46.1%) (all p < 0.0005). Also, they had longer lengths of stay (8.1 +/- 7.1 vs. 6.8 +/- 5.3 days, p < 0.00005) and greater risk for in-hospital death (21.4% vs. 7.2%; p < 0.0005). Patients with CHF were less likely to receive aspirin (75.7% vs. 89.0%), heparin (74.6% vs. 91.1%), oral beta-blockers (27.0% vs. 41.7%), fibrinolytics (33.4% vs. 58.0%), or primary angioplasty (8.6% vs. 14.6%), and more likely to receive angiotensin-converting enzyme inhibitors (25.4% vs. 13.0%). Congestive heart failure on admission was one of the strongest predictors of in-hospital death (adjusted odds ratio 1.68; 95% confidence interval 1.62, 1.75). CONCLUSIONS: Patients with AMI presenting with CHF are at higher risk for adverse in-hospital outcomes. Despite this, they are less likely to be treated with reperfusion therapy and medications with proven mortality benefit.

Adrenergic beta-Antagonists↗