The need for resources for clinical research: proceedings of a policy conference held at the European Heart House, 27-28 June 2002: executive summary.

The medical profession, in particular cardiologists, acknowledge the fact that during the last 30 years, much of the progress made in the field of medicine has resulted from fruitful and close collaboration between academia and the pharmaceutical industry. However, during the last decade, this relationship has changed considerably. The industry increasingly carries out its own research, development of drugs and trials, according to its own agenda.

Anti-platelet factor 4/heparin antibodies: an independent predictor of 30-day myocardial infarction after acute coronary ischemic syndromes.

Background: We postulated that antibodies to platelet factor 4/heparin complex might contribute to recurrent ischemic events in patients with acute coronary syndrome.

Methods And Results: We analyzed serum from patients enrolled in the placebo/unfractionated heparin arm of the GUSTO IV-ACS trial who had high likelihood of prior heparin exposure. We selected 109 patients without thrombocytopenia with the 30-day primary end point (death, myocardial infarction [MI], or revascularization) and 109 age-, gender-, and race-matched controls who did not achieve the primary end point.

Serum level of the antiinflammatory cytokine interleukin-10 is an important prognostic determinant in patients with acute coronary syndromes.

Background: Convincing evidence suggests that atherosclerosis is an inflammatory disease. The inflammatory response is an important determinant of atherosclerotic plaque instability. Therefore, we investigated the prognostic impact of key inflammatory players, namely the inflammatory marker C-reactive protein (CRP) and the antiinflammatory cytokine interleukin-10 (IL-10), in patients with acute coronary syndromes.

Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome: a GUSTO-IV substudy.

Objectives: We sought to evaluate C-reactive protein (CRP) and troponin T (TnT) as predictors of risk of the individual end points of mortality and myocardial infarction (MI) in a large cohort of patients with acute coronary syndrome (ACS).

Background: Both CRP and TnT predict risk of future coronary events in patients with ACS. However, the relationships between the levels of the markers and the individual end points are still unclear.

Soluble CD40 ligand in acute coronary syndromes.

Background: CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syndromes.

Methods: Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who had previously been enrolled in a randomized trial comparing abciximab with placebo before coronary angioplasty and in 626 patients with acute chest pain.

Acute myocardial infarction.

Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view.

Excellent survival and low incidence of arrhythmias, stroke and heart failure long-term after surgical ASD closure at young age. A prospective follow-up study of 21-33 years.

Aims: Although studies have suggested good long-term results, arrhythmias, pulmonary hypertension and left ventricular dysfunction are mentioned as sequelae long-term after surgical atrial septal defect closure at young age. Most studies were performed only by questionnaire and in a retrospective manner. The long-term outcome is very important with regard to future employment and acceptance on insurance schemes.

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.

Prognostic significance of angiogenic growth factor serum levels in patients with acute coronary syndromes.

Background: In patients with acute coronary syndromes, compensatory processes are initiated, including angiogenesis and endothelial regeneration of ruptured or eroded plaques. Angiogenic growth factors like vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) are upregulated during ischemia. However, it is unknown whether their serum levels are related to clinical outcome.

Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA.

Aims: Treatment with the glycoprotein IIb/IIIa receptor antagonist abciximab before and during coronary intervention in refractory unstable angina improves early outcome. We collected 4-year follow-up data to assess whether this benefit is sustained. Additionally, we investigated the predictive value of baseline troponin T and CRP for long-term cardiovascular events.

Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one-year survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV--Acute Coronary Syndrome) Trial.

Background: This study was designed to investigate long-term effects of the glycoprotein IIb/IIIa inhibitor abciximab in patients with acute coronary syndrome without ST elevation who were not scheduled for coronary intervention.

Methods And Results: A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. They were randomized to abciximab bolus and 24-hour infusion, abciximab bolus and 48-hour infusion, or matching placebo.

Frequency, patient characteristics, and outcomes of mild-to-moderate heart failure complicating ST-segment elevation acute myocardial infarction: lessons from 4 international fibrinolytic therapy trials.

Background: There is a paucity of data on the incidence of mild-to-moderate heart failure (HF) complicating ST-segment elevation acute myocardial infarction (MI) and its impact on short-term outcomes. Our objective was to determine the incidence, timing, and consequences of mild-to-moderate HF complicating acute MI.

Methods: We examined the occurrence of death or death/recurrent MI (re-MI) in patients enrolled in the Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I), the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO IIb), the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III), and Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-II) trials, which examined different fibrinolytic therapies for MI.

Safety and efficacy of abciximab combined with dalteparin in treatment of acute coronary syndromes.

Aims: The safety and efficacy of abciximab in addition to low-molecular-weight-heparin as the primary medical treatment of acute coronary syndromes has not previously been investigated.

Methods And Results: The GUSTO IV-ACS trial included 7800 patients with chest pain and either ST-segment depression or a positive troponin test. They were randomized to abciximab for 24 h, 48 h or placebo.

Platelet GP IIb/IIIa receptor blockers for failed thrombolysis in acute myocardial infarction, alone or as adjunct to other rescue therapies; single centre retrospective analysis of 548 consecutive patients with acute myocardial infarction.

In order to study the safety of 'rescue' strategies in the treatment of patients with failed thrombolysis, all 548 patients admitted with evolving myocardial infarction to the Thoraxcenter, Rotterdam, from January 1997 until April 1999 were reviewed. Of these patients, 49% had received thrombolysis. Of patients treated with thrombolysis and not referred from other hospitals (n = 154) 36% received rescue therapy for failed thrombolysis.

Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI-SK study.

Aims: To establish whether the addition of enoxaparin (a low-molecular-weight heparin) to streptokinase therapy improves early and sustained coronary patency and clinical outcome in patients with evolving myocardial infarction.

Methods And Results: A total of 496 patients with acute myocardial infarction treated with streptokinase were randomized to an intravenous bolus (30 mg) and subcutaneous injections (1mg x kg(-1), twice daily) of enoxaparin (n=253), or placebo (n=243) for 3-8 days. The median duration of treatment in both groups was 5 days.

A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS).

Aims: To better delineate the characteristics, treatments, and outcomes of patients with acute coronary syndromes (ACS) in representative countries across Europe and the Mediterranean basin, and to examine adherence to current guidelines.

Methods And Results: We performed a prospective survey (103 hospitals, 25 countries) of 10484 patients with a discharge diagnosis of acute coronary syndromes. The initial diagnosis was ST elevation ACS in 42.

Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes.

Background: The prognosis of ventricular arrhythmias among patients with non-ST-elevation acute coronary syndromes is unknown. We studied the incidence, predictors, and outcomes of sustained ventricular arrhythmias in 4 large randomized trials of such patients.

Methods And Results: We pooled the datasets of the Global Use of Streptokinase and tPA for Occluded Arteries (GUSTO)-IIb, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-A, and PARAGON-B trials (n=26 416).

Does eptifibatide confer a greater benefit to patients with unstable angina than with non-ST segment elevation myocardial infarction? Insights from the PURSUIT Trial.

Aims: To evaluate the differential effects of eptifibatide therapy on unstable angina vs non-ST elevation myocardial infarction at enrollment, since the separate impact on these two major diagnostic subsets of acute coronary syndrome patients has not been fully investigated.

Methods And Results: We examined the 9461 patients in the PURSUIT trial (conducted between 1995 and 1997) to compare the effects of eptifibatide on unstable angina and myocardial infarction. The study showed greater and more consistent effects of eptifibatide therapy on unstable angina than non-ST elevation myocardial infarction in reducing 30-day death/(re)infarction (from the unadjusted rate of 13.

Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction.

Background: Among patients with suspected acute coronary syndromes, cardiac troponin T levels have prognostic value. However, there is concern that renal dysfunction may impair the prognostic value, because cardiac troponin T may be cleared by the kidney.

Methods: We analyzed the outcomes in 7033 patients enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries IV trial who had complete base-line data on troponin T levels and creatinine clearance rates.