Usefulness of prodromal unstable angina pectoris in predicting better survival and smaller infarct size in acute myocardial infarction (The InTIME-II Prodromal Symptoms Substudy).

Prodromal unstable angina on presentation is a significant predictor of smaller infarct size, reflected by smaller creatine kinase-MB and creatine kinase total measurements and lower 30-day, 6-month, and 5-year mortality. These findings suggest that prodromal unstable angina is an important physiologic marker that should be routinely collected for risk stratification.

Association of the Fibonacci Cascade with the distribution of coronary artery lesions responsible for ST-segment elevation myocardial infarction.

This is the first study to demonstrate the appearance of the Fibonacci Cascade within the distribution of coronary artery lesions in the human heart. The propensity for this ratio to appear in nature may also be because this ratio optimizes the efficiency of packing structures in a limited space in such a way that wasted space is minimized and the supply of energy or nutrients is optimized.

Early and long-term clinical outcomes associated with reinfarction following fibrinolytic administration in the Thrombolysis in Myocardial Infarction trials.

Objectives: We hypothesized that early recurrent myocardial infarction (MI) following fibrinolytic administration would be assessed with higher mortality at both 30 days and 2 years.

Background: Although early recurrent MI after fibrinolytic therapy has been associated with increased early mortality in the acute MI setting, its relation to long-term mortality has not been fully explored.

Methods: Mortality data were ascertained in 20,101 patients enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 4, 9, and 10B and Intravenous NPA for the Treatment of Infarcting Myocardium Early (InTIME-II) acute MI trials.

Meta-analysis of corticosteroid treatment in acute myocardial infarction.

Acute and chronic inflammation play a central role in the pathophysiology of atherosclerosis. Corticosteroids are the gold standard anti-inflammatory agent and may have a role in treating acute myocardial infarction. However, concern exists regarding the potential for impaired wound healing and wall thinning.

Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial.

Objectives: The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI).

Background: Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established.

Use of low-molecular-weight heparins in the management of acute coronary artery syndromes and percutaneous coronary intervention.

Context: Low-molecular-weight heparins (LMWHs) possess several potential pharmacological advantages over unfractionated heparin as an antithrombotic agent.

Objective: To systematically summarize the clinical data on the efficacy and safety of LMWHs compared with unfractionated heparin across the spectrum of acute coronary syndromes (ACSs), and as an adjunct to percutaneous coronary intervention (PCI).

Data Sources: We searched MEDLINE for articles from 1990 to 2002 using the index terms heparin, enoxaparin, dalteparin, nadroparin, tinzaparin, low molecular weight heparin, myocardial infarction, unstable angina, coronary angiography, coronary angioplasty, thrombolytic therapy, reperfusion, and drug therapy, combination.

Elevated serum creatinine is associated with 1-year mortality after acute myocardial infarction.

Background: Cardiovascular mortality is high in individuals with end-stage renal disease. However, less is known about the prognostic importance of moderate renal insufficiency in patients with acute myocardial infarction.

Methods: We studied all patients with acute myocardial infarction admitted through the emergency department to an urban, academic hospital over 1 year.

Evaluation of the time saved by prehospital initiation of reteplase for ST-elevation myocardial infarction: results of The Early Retavase-Thrombolysis in Myocardial Infarction (ER-TIMI) 19 trial.

Objectives: The Early Retavase-Thrombolysis In Myocardial Infarction (ER-TIMI) 19 trial tested the feasibility of prehospital initiation of the bolus fibrinolytic reteplase (rPA) and determined the time saved by prehospital rPA in the setting of contemporary emergency cardiac care.

Background: Newer bolus fibrinolytics have undergone only limited evaluation for prehospital administration. In addition, as door-to-drug times have decreased, the relevance of findings from prior trials of prehospital fibrinolysis has become less certain.

Identification of patients at high risk for death and cardiac ischemic events after hospital discharge.

Background: Patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) remain at risk for death and cardiac ischemic events after being discharged from the hospital.

Methods: We examined whether the Thrombolysis In Myocardial Infarction (TIMI) risk score for UA/NSTEMI, ascertained at presentation in patients enrolled in the TIMI 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI (ESSENCE) trials, could be used to identify patients at high risk for major cardiac events after hospital discharge.

Results: There were a total of 1218 major cardiac events, defined as death, nonfatal myocardial infarction, or urgent revascularization, by day 43.

Determinants of improvement in epicardial flow and myocardial perfusion for ST elevation myocardial infarction; insights from TIMI 14 and InTIME-II.

Background: When evaluating new reperfusion regimens for ST elevation MI, it is important to adjust for factors that influence the likelihood of achieving normal epicardial flow and complete ST resolution.

Methods And Results: A total of 610 patients from TIMI 14 contributed to the angiographic analyses. The electrocardiographic analyses were based on 544 patients from TIMI 14 and 763 patients from InTIME-II.

A simple risk index for rapid initial triage of patients with ST-elevation myocardial infarction: an InTIME II substudy.

Background: Rapid, effective triage is integral to emergency cardiac care of patients with ST-elevation myocardial infarction (STEMI). Available models for predicting mortality in STEMI include up to 45 variables, but have consistently shown advanced age, increased heart rate, and decreased blood pressure to be among the strongest predictors.

Methods: On the basis of observed risk relations among 13,253 patients with STEMI from the InTIME II trial, we developed and assessed a simple risk index using age, heart rate, and systolic blood pressure (SBP) for predicting mortality over 30 days: (heart rate x [age/10](2))/SBP.

Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction.

Aims: To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction.

Methods And Results: We studied 15,078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities.

Early coronary intervention following pharmacologic therapy for acute myocardial infarction (the combined TIMI 10B-TIMI 14 experience).

Earlier studies have suggested that immediate percutaneous coronary intervention (PCI) following thrombolytic therapy for acute myocardial infarction (AMI) is associated with an increase in adverse events and that routine PCI in this setting has offered no advantage over a conservative strategy. To reassess this issue in a more recent era, we evaluated 1,938 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B and 14 trials of AMI. Patients in TIMI 10B were randomized to receive tissue plasminogen activator or TNK tissue plasminogen activator, whereas patients in TIMI 14B trial were randomized to receive thrombolytic therapy with or without abciximab.

Application of the TIMI risk score for ST-elevation MI in the National Registry of Myocardial Infarction 3.

Context: The Thrombolysis in Myocardial Infarction (TIMI) risk score for ST-elevation myocardial infarction (STEMI) is a simple integer score for bedside risk assessment of patients with STEMI. Developed and validated in multiple clinical trials of fibrinolysis, the risk score has not been validated in a community-based population.

Objective: To validate the TIMI risk score in a population of STEMI patients reflective of contemporary practice.

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis.

Geographic variation in patient and hospital characteristics, management, and clinical outcomes in ST-elevation myocardial infarction treated with fibrinolysis. Results from InTIME-II.

Aims: We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with lanoteplase for myocardial infarction.

Methods And Results: We compared baseline characteristics, management, and outcomes in four regions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K.

Bolus fibrinolytic therapy in acute myocardial infarction.

Context: New bolus fibrinolytics derived from the human tissue-type plasminogen activator (tPA) have emerged as a means of dissolution of occlusive thrombosis associated with acute myocardial infarction.

Objective: To review the new bolus fibrinolytic drugs derived from tPA: reteplase, lanoteplase, and tenecteplase.

Data Sources: The MEDLINE, EMBASE, and Current Contents databases were searched for articles from 1983 to 2001, using the index terms pharmacokinetics, pharmacodynamics, plasminogen activator, reteplase, lanoteplase, and tenecteplase.

Lower-dose heparin with fibrinolysis is associated with lower rates of intracranial hemorrhage.

Background: The optimal heparin dose as an adjunct to fibrinolysis and its role in causing intracranial hemorrhage (ICH) is unclear.

Methods: We reviewed the heparin regimens and rates of ICH in 3 sets of recent fibrinolytic trials: (1) studies with accelerated recombinant tissue plasminogen activator (TPA, alteplase) plus intravenous heparin, in which the heparin regimen was changed during the course of the trial; (2) phase III trials with accelerated TPA plus intravenous heparin; and (3) trials of new single-bolus fibrinolytic agents.

Results: Lower rates of ICH were observed among studies of accelerated TPA that reduced the heparin dose mid-trial (TIMI 9A --> 9B: 1.

Comparison of Argatroban and Hirudin for the Reperfusion of Thrombotic Arterial Occlusion by Tissue Plasminogen Activator.

Despite theoretical advantages of direct thrombin inhibitors, recent clinical studies failed to show the superiority of hirudin over heparin in patients with acute coronary syndromes. However, these inhibitors have important in vitro differences for the inhibition of clot-bound thrombin that may translate into different in vivo relative efficacy. The effects of two direct thrombin inhibitors, argatroban and hirudin, on the reperfusion of thrombotic arterial occlusion by t-PA were compared.

New Thrombolytic Agents: Does Direct Angioplasty Still Have a Role?

The optimal method of reperfusion for patients with ST-segment elevation acute myocardial infarction has been a point of controversy over the last two decades. Tenecteplase and reteplase are comparable to accelerated-dose alteplase but more convenient because they can be delivered as a bolus. Combination regimens represent a further advance in reperfusion therapy; planned and ongoing studies will evaluate the clinical efficacy and safety of combination therapy.

Comparison of a 60- versus 90-minute determination of ST-segment resolution after thrombolytic therapy for acute myocardial infarction. In TIME-II Investigators. Intravenous nPA for Treatment of Infarcting Myocardium Early-II.

Determination of ST-segment resolution 60 minutes after the administration of thrombolytic therapy allows accurate risk stratification for mortality and congestive heart failure. Patients with complete ST resolution at 60 minutes tended to be at lower risk for 30-day mortality than patients with complete ST resolution at 90 minutes.

ST-segment resolution and infarct-related artery patency and flow after thrombolytic therapy. Thrombolysis in Myocardial Infarction (TIMI) 14 investigators.

Because patients who fail to achieve reperfusion after thrombolytic therapy remain at high risk for morbidity and mortality, noninvasive measures of infarct-related artery (IRA) patency are needed to identify candidates for rescue interventions. We prospectively studied 444 patients from the Thrombolysis In Myocardial Infarction (TIMI) 14 trial with interpretable baseline and 90 minute 12-lead electrocardiograms. The percent resolution of ST-segment deviation from baseline to 90 minutes was compared with 90-minute IRA TIMI flow grade, as determined in an angiographic core laboratory.

Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14. The Thrombolysis in Myocardial Infarction (TIMI) 14 Investigators.

Aims Abciximab has previously been shown to enhance thrombolysis and improve myocardial perfusion when combined with reduced doses of alteplase. The purpose of the reteplase phase of TIMI 14 was to evaluate the effects of abciximab when used in combination with a reduced dose of reteplase for ST-elevation myocardial infarction. Methods and Results Patients (n=299) with ST-elevation myocardial infarction were treated with aspirin and randomized to a control arm with standard dose reteplase (10+10 U given 30 min apart) or abciximab (bolus of 0.