The clinician as investigator: participating in clinical trials in the practice setting.

The rapid development of new drugs, therapies, and devices has created a dramatic increase in the number of trials needed to properly evaluate them. The majority of patients treated today, many of whom could be eligible for participation in these studies, are seen in community hospitals and medical practices that are not affiliated with an academic medical center. Thus, there is a demonstrable need for physicians in private practice to enlist as investigators in these trials.

Effect of multielement intravascular ultrasound on the anticoagulant potency of enoxaparin.

Two patients, treated with enoxaparin and eptifibatide, developed significant guide catheter-associated thrombus while undergoing intravascular ultrasound (IVUS). Using an ex vivo assay, we found that activation of a multielement IVUS catheter resulted in a decrease in anti-Xa activity and a decrease in clot formation time. This effect occurred rapidly and repeatedly after activation of the IVUS catheter.

Bleeding events with abciximab in acute coronary syndromes without early revascularization: An analysis of GUSTO IV-ACS.

Background: The glycoprotein IIb/IIIa receptor antagonist abciximab reduces the risk of thrombotic complications with percutaneous coronary intervention, but also has been associated with higher bleeding rates.

Methods: In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, abciximab (either a 24-hour or 48-hour infusion) was compared with placebo in 7800 patients with an acute coronary syndrome. During study drug administration, 2% of the patients underwent a revascularization procedure.

Implications of elevated cardiac troponin T in ambulatory patients with heart failure: a prospective analysis.

Background: Elevated concentrations of cardiac troponin T (TnT) have been reported in patients hospitalized for decompensated heart failure (HF). We assessed whether elevated TnT levels are associated with the severity, etiology, and prognosis of HF in stable, ambulatory patients.

Methods: From 1998-1999, we prospectively collected data from 136 ambulatory patients with HF, New York Heart Association functional class II to IV, ejection fraction < or =35%, and no recent unstable angina, myocardial infarction, surgery, or coronary revascularization.

Percutaneous coronary intervention in a patient with immune thrombocytopenia purpura.

The appropriate regimen of platelet inhibitors that should be used in patients with immune thrombocytopenia purpura (ITP; formerly called idiopathic thrombocytopenic purpura) who are undergoing percutaneous coronary intervention is unclear. We report the case of a patient with ITP who underwent two separate coronary interventions. The first involved the use of aspirin and a cutting balloon to treat obstructive disease of the left circumflex.

Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes.

Aim: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS).

Methods And Results: Peak CK-MB ratios (peak CK-MB level/upper limit of normal [ULN]) after PCI were analysed in 6164 patients with NSTE ACS from four randomized trials who underwent in-hospital PCI. We excluded 696 patients with elevated CK or CK-MB levels <24h before PCI; the primary analysis included 2384 of the remaining 5468 patients (43.

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.

Significance of atrial fibrillation during acute myocardial infarction, and its current management: insights from the GUSTO-3 trial.

The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)-3 atrial fibrillation (AF) substudy assessed the prognostic significance of AF during acute myocardial infarction (AMI), the use of antiarrhythmic therapies, and whether different antiarrhythmic therapies were associated with different outcomes. The timing of the onset of AF relative to other post-AMI complications was recorded in the study. Of the 13,858 patients who were in sinus rhythm at the time of enrolment into GUSTO-3, 906 (6.

Distance from the coronary ostium to the culprit lesion in acute ST-elevation myocardial infarction and its implications regarding the potential prevention of proximal plaque rupture.

Background: Shorter distances from the coronary ostia to culprit lesions have been associated with a higher incidence of adverse outcomes in ST elevation acute myocardial infarction (STEMI). As drug-eluting stents are associated with low rates of restenosis and formation of a stable intima, we sought to develop a mathematical model to estimate how far down the coronary artery a drug-eluting stent would have to be placed to theoretically mitigate the risk of proximal plaque rupture.

Objectives And Methods: Distances from the ostia to the end of the culprit lesions were planimetered in 1,914 patients from the TIMI 14, INTEGRITI, FASTER and ENTIRE/TIMI 23 trials.

A randomized, placebo-controlled trial of early eptifibatide for non-ST-segment elevation acute coronary syndromes.

Background: The acute benefits of platelet glycoprotein IIb/IIIa inhibitors for non-ST-segment elevation acute coronary syndromes (NSTE ACS) remain unclear.

Methods: In this pilot trial, 311 patients with NSTE ACS were randomly assigned in the emergency department to double-blinded therapy with eptifibatide or placebo for 12 to 24 hours before crossover to open-label eptifibatide. Serial creatine-kinase MB (CK-MB) and quantitative cardiac troponin T levels were collected during the first 24 hours to assess the impact of early platelet glycoprotein IIb/IIIa blockade on infarct size as measured by cardiac markers.

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

Purpose: To investigate the prognostic importance of new small Q waves following an acute coronary syndrome.

Methods: We assessed 6-month mortality in 10501 patients with non-ST-elevation acute coronary syndromes who had survived 30 days and had both admission and 30-day electrocardiograms. Patients were stratified by whether they had no new Q waves (n = 9447), new 30- to 40-ms Q waves (n = 733), or new > or =40-ms Q waves (n = 321).

The anticoagulant therapy with bivalirudin to assist in the performance of percutaneous coronary intervention in patients with heparin-induced thrombocytopenia (ATBAT) study: main results.

Up to 5% of patients given heparin develop heparin-induced thrombocytopenia (HIT). These patients may need anticoagulation for acute coronary syndromes (ACS) or percutaneous coronary intervention (PCI), a clinical challenge given the limited alternatives. In a prospective, open-label study, we evaluated the safety and efficacy of bivalirudin in patients with HIT or HIT with thrombotic syndrome (HITTS) undergoing PCI.

Changing the model of care for patients with acute coronary syndromes.

Acute coronary syndromes (ACS) represent a major cause of morbidity and mortality for patients with cardiovascular disease, but evidence-based therapies shown to improve outcomes for ACS are often underused in clinically eligible patients. Although clinical practice guidelines have been developed to provide standards for the diagnosis and treatment of patients with ACS and to provide physicians with a framework for clinical decision-making, multiple obstacles have hindered their implementation and questions remain about the applicability of guidelines for diverse clinical situations. Systematic reviews of quality-improvement studies have shown that multifaceted approaches using targeted educational interventions, creation of quality standards, and regular performance feedback are needed to ensure sustained improvements in care.

Intra-aortic balloon counterpulsation in US and non-US centres: results of the Benchmark Registry.

Aims: To examine differences in patient characteristics and outcomes in 19636 patients enrolled in the USA and 3027 patients enrolled in other countries undergoing intra-aortic balloon pump (IABP) counterpulsation.

Methods And Results: Indications for IABP use; a larger percentage of US patients were identified as 'early support and stabilization for angiography or angioplasty' (21.1% US vs 11.

Prevalence of conventional risk factors in patients with coronary heart disease.

Context: It is commonly suggested that more than 50% of patients with coronary heart disease (CHD) lack any of the conventional risk factors (cigarette smoking, diabetes, hyperlipidemia, and hypertension). This claim implies that other factors play a significant role in CHD and has led to considerable interest in nontraditional risk factors and genetic causes of CHD.

Objective: To determine the prevalence of the 4 conventional risk factors among patients with CHD.

Effect of eptifibatide for acute coronary syndromes: rapid versus late administration--therapeutic yield on platelets (The EARLY Platelet Substudy).

Background: Receptors other than GP IIb/IIIa may mediate leukocyte-platelet-endothelial interactions that obstruct the microvasculature in acute coronary syndromes (ACS) and cause microinfarcts. The effect of eptifibatide on these receptors was investigated in a substudy of the EARLY Trial.

Methods: Patients received early (in the Emergency Department, n = 27) or late (12-24 h, n = 28) eptifibatide.

Relation between hospital intra-aortic balloon counterpulsation volume and mortality in acute myocardial infarction complicated by cardiogenic shock.

Background: Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation (IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock.

Methods And Results: We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998.

Frequency of stent thrombosis after acute coronary syndromes (from the SYMPHONY and 2nd SYMPHONY trials).

We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice.

Contemporary utilization and outcomes of intra-aortic balloon counterpulsation in acute myocardial infarction: the benchmark registry.

Objectives: We sought to examine contemporary utilization patterns and clinical outcomes in patients with acute myocardial infarction (AMI) requiring intra-aortic balloon pump (IABP) counterpulsation.

Background: Despite increasing experience with and broadened indications for intra-aortic counterpulsation, the current indications, associated complications, and clinical outcomes of IABP use in AMI are unknown.

Methods: Between June 1996 and August 2001, data were prospectively collected from 22,663 consecutive patients treated with aortic counterpulsation at 250 medical centers worldwide; 5,495 of these patients had AMI.

Prognostic value of isolated troponin elevation across the spectrum of chest pain syndromes.

The risk of death or recurrent myocardial infarction (MI) in patients with chest pain and baseline isolated troponin elevation is unclear. To determine the early and short-term risk of death or MI associated with isolated troponin elevation across a spectrum of chest pain syndromes, we used baseline creatine kinase (CK)-MB and troponin data from the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) B troponin substudy, the Global Utilization of Strategies To Open Occluded Coronary Arteries (GUSTO) IIa troponin substudy, and the Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) study. Patients were grouped into 1 of 4 categories based on marker status (troponin-positive/CK-MB-positive, troponin-positive/CK-MB-negative, troponin-negative/CK-MB-positive, or troponin-negative/CK-MB-negative).

Sustained ventricular arrhythmias and mortality among patients with acute myocardial infarction: results from the GUSTO-III trial.

Background: In many patients, ventricular arrhythmias will develop early after acute myocardial infarction. We studied the incidence, timing, and outcomes of such arrhythmias in the international Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO)-III trial.

Methods: We identified independent predictors of inhospital ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared 30-day and 1-year mortality rates of patients who did (n = 1121) and did not (n = 13,921) have these arrhythmias during the index hospitalization.

Troponin: an important prognostic marker and risk-stratification tool in non-ST-segment elevation acute coronary syndromes.

Over the past decade, there has been a progressive evolution of cardiac marker testing in patients with acute coronary syndromes (ACS). This has not only resulted in a dramatic shift in how we view the diagnosis of myocardial infarction (MI), but it has also extended the role of cardiac marker testing into risk stratification and guidance of treatment decisions. By the year 2000, the development of highly sensitive and cardiac-specific troponin assays had resulted in a consensus change in the definition of MI, placing increased emphasis on cardiac-marker testing with troponins as the new gold standard.