Improving academic leadership and oversight in large industry-sponsored clinical trials: the ARO-CRO model.

Standards for clinical trial design, execution, and publication have increased in recent years. However, the current structure for interaction among the pharmaceutical sponsor funding a drug or device development program, the contract research organization (CRO) that typically assists in executing the trial, regulatory agencies, and academicians, provides inadequate leadership and oversight of the development process. Conventional academic steering committees are not provided with the independent infrastructure by which to verify statistical analyses and conclusions regarding safety and efficacy.

Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08).

Objective: PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) enrolled patients with type 2 diabetes and preexisting cardiovascular disease. These patients were at high risk for heart failure, so any therapeutic benefit could potentially be offset by risk of associated heart failure mortality. We analyzed the heart failure cases to assess the effects of treatment on morbidity and mortality after reports of serious heart failure.

The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study.

Objectives: This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI).

Background: People with type 2 diabetes have an increased incidence of MI compared with the general population. Those with diabetes and MI have a worse prognosis than nondiabetic patients with cardiovascular disease.

Drug-induced thrombocytopenia and thrombosis: evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial.

Objective: To assess etiology and impact of thrombocytopenia in a large oral glycoprotein (GP) IIb/IIIa inhibitor trial.

Background: Heparin is known to cause thrombocytopenia, and in some of these patients thrombosis. GP IIb/IIIa inhibitors are also associated with thrombocytopenia.

Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data.

Background: Several randomized trials have compared atrial-based (dual-chamber or atrial) pacing with ventricular pacing in patients with bradycardia. No trial has shown a mortality reduction, and only 1 small trial suggested a reduction in stroke. The goal of this review was to determine whether atrial-based pacing prevents major cardiovascular events.

Relationship between uncontrolled risk factors and C-reactive protein levels in patients receiving standard or intensive statin therapy for acute coronary syndromes in the PROVE IT-TIMI 22 trial.

Objectives: This study sought to evaluate what set of factors correlate with higher or lower C-reactive protein (CRP) levels in patients receiving standard and intensive statin therapy.

Background: C-reactive protein levels in blood are becoming recognized as a potential means of monitoring cardiovascular risk. Although statin therapy is known to reduce CRP levels, many patients have a high CRP level despite statin therapy.

Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.

Background: Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes.

Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome.

Background: Chlamydia pneumoniae has been found within atherosclerotic plaques, and elevated titers of antibody to this organism have been linked to a higher risk of coronary events. Pilot studies have suggested that antibiotic treatment may reduce the risk of cardiovascular events.

Methods: We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and evaluated the efficacy of long-term treatment with gatifloxacin, a bactericidal antibiotic known to be effective against C.

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.

Background: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death.

Methods: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication.

Intensive versus moderate lipid lowering with statins after acute coronary syndromes.

Background: Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear.

Methods: We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke.