Developing, Planning and Conducting an Interim Analysis: Lessons From the DEVOTE Cardiovascular Outcomes Trial (Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events).

Background: In 2013, a randomized, double-blind, active comparator-controlled, event-driven cardiovascular outcomes trial (DEVOTE) was initiated to compare the cardiovascular safety of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes at high risk of cardiovascular events. The FDA agreed that an interim analysis could form the basis for an early regulatory approval. We report here the operational model developed to support the DEVOTE interim analysis and the results.

Underuse of an invasive strategy for patients with diabetes with acute coronary syndrome: a nationwide study.

Background: Guidelines recommend an early invasive strategy for patients with diabetes with acute coronary syndromes (ACS). We investigated if patients with diabetes with ACS are offered coronary angiography (CAG) and revascularisation to the same extent as patients without diabetes.

Methods And Results: The study is a nationwide cohort study linking Danish national registries containing information on healthcare.

Outcomes of patients calling emergency medical services for suspected acute cardiovascular disease.

Adequate health care is increasingly dependent on prehospital systems and cardiovascular (CV) disease remains the most common cause for hospital admission. However the prevalence of CV dispatches of emergency medical services (EMS) is not well reported and survival data described in clinical trials and registries are subject to selection biases. We aimed to describe the prevalence and prognosis of acute CV disease and the effect of invasive treatment, in an unselected and consecutive prehospital cohort of 3,410 patients calling the national emergency telephone number from 2005 to 2008 with follow-up in 2013.

Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease: a registry-based cohort study.

Aims: To evaluate risk of hospitalization due to cardiovascular disease (CVD) and repeat coronary angiography (CAG) in stable angina pectoris (SAP) with no obstructive coronary artery disease (CAD) versus obstructive CAD, and asymptomatic reference individuals.

Methods And Results: We followed 11,223 patients with no prior CVD having a first-time CAG in 1998-2009 due to SAP symptoms and 5,695 asymptomatic reference individuals from the Copenhagen City Heart Study through registry linkage for 7.8 years (median).

GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody.

Glucagon-like peptide 1 (GLP-1) analogs are increasingly being used in the treatment of type 2 diabetes. It is clear that these drugs lower blood glucose through an increase in insulin secretion and a lowering of glucagon secretion; in addition, they lower body weight and systolic blood pressure and increase heart rate. Using a new monoclonal antibody for immunohistochemistry, we detected GLP-1 receptor (GLP-1R) in important target organs in humans and monkeys.

Symptoms of angina pectoris increase the probability of disability pension and premature exit from the workforce even in the absence of obstructive coronary artery disease.

Aims: To evaluate probabilities of disability pension (DP) and premature exit from the workforce (PEW) in patients with stable angina symptoms and no obstructive coronary artery disease (CAD) at angiography compared with obstructive CAD and asymptomatic reference individuals.

Methods And Results: We followed 4303 patients with no prior cardiovascular disease having a first-time coronary angiography (CAG) in 1998-2009 due to stable angina symptoms and 2772 reference individuals from the Copenhagen City Heart Study, all aged <65 years, through registry linkage until 2009 for DP and PEW. Five-year age-adjusted DP-free survival probabilities for reference individuals, patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1 stenotic coronary vessel (1VD), 2VD, and 3VD, respectively, were 0.

Reperfusion delay in patients treated with primary percutaneous coronary intervention: insight from a real world Danish ST-segment elevation myocardial infarction population in the era of telemedicine.

Background: Reperfusion delay in ST-segment elevation myocardial infarction (STEMI) predicts adverse outcome. We evaluated time from alarm call (system delay) and time from first medical contact (PCI-related delay), where fibrinolysis could be initiated, to balloon inflation in a pre-hospital organization with tele-transmitted electrocardiograms, field triage and direct transfer to a 24/7 primary percutaneous coronary intervention (PPCI) center.

Methods And Results: This was a single center cohort study with long-term follow-up in 472 patients.

Persistent angina: highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris.

Aims: To evaluate persistent angina in stable angina pectoris with no obstructive coronary artery disease (CAD) compared to obstructive CAD and its relation to long-term anxiety, depression, quality of life (QOL), and physical functioning.

Methods And Results: We invited 357 patients (men = 191; women = 166; response rate 83 %) with no prior cardiovascular disease who had a first-time coronary angiography (CAG) in 2008-2009 due to suspected stable angina to participate in a questionnaire survey in 2011 with the Seattle Angina Questionnaire and the Hospital Anxiety and Depression Scale as key elements. Long-term persistent angina (i.

Long-term benefits and risks of drug-eluting compared to bare-metal stents in patients with versus without chronic kidney disease.

Aims: Chronic kidney disease (CKD) is associated with worse outcomes in patients with coronary artery disease (CAD). How CKD influences the benefit-risk balance of drug-eluting stents (DES) versus bare-metal stents (BMS) is less known.

Methods And Results: In the multicentre BASKET-PROVE trial, 2314 patients in need of large coronary stenting (≥ 3.

Prognosis and treatment in patients admitted with acute myocardial infarction on weekends and weekdays from 1997 to 2009.

Background: Less invasive treatment and poorer outcomes have been shown among patients admitted with acute myocardial infarction (AMI) on weekends compared to weekdays.

Objectives: To investigate the 'weekend-effect' on mortality in patients with AMI.

Methods: Using nationwide registers we identified 92,164 patients aged 30-90 years who were admitted to a Danish hospital with a first AMI from 1997 to 2009.

Osteoprotegerin predicts long-term outcome in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

Background: Osteoprotegerin (OPG) is a glycoprotein with a regulatory role in immune, skeletal and vascular systems. Data suggest that high circulating OPG levels are associated with an increased risk of cardiovascular disease. We analyzed the association between OPG and long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI).

High-degree atrioventricular block complicating ST-segment elevation myocardial infarction in the era of primary percutaneous coronary intervention.

Aims: Primary percutaneous coronary intervention (pPCI) has replaced thrombolysis as treatment-of-choice for ST-segment elevation myocardial infarction (STEMI). However, the incidence and prognostic significance of high-degree atrioventricular block (HAVB) in STEMI patients in the pPCI era has been only sparsely investigated. The objective of this study was to assess the incidence, predictors and prognostic significance of HAVB in STEMI patients treated with pPCI.

Significance of the invasive strategy after acute myocardial infarction on prognosis and secondary preventive medication: a nationwide study of 6364 women and 11,915 men.

Objective: To describe gender-specific long-term outcome and initiation of secondary preventive medication among patients with acute myocardial infarction (AMI).

Design: Observational cohort study.

Setting: Nationwide registries.

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

Aims: Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus.

Methods And Results: We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison.

Tissue Doppler echocardiography reveals impaired cardiac function in patients with reversible ischaemia.

Aims: To determine if echocardiographic tissue Doppler imaging (TDI) performed at rest detects reduced myocardial function in patients with reversible ischaemia.

Methods And Results: Eighty-four patients with angina pectoris, no previous history of ischaemic heart disease and normal left ventricular ejection fraction were examined with colour TDI, single-photon emission computed tomography (SPECT), and coronary angiography (CAG). Patients with a normal SPECT (n= 42) constituted the control group and patients with a positive SPECT (n= 42) were divided into patients with (true-positive SPECT, n= 30) or without (false-positive SPECT, n= 12) significant coronary stenoses assessed by CAG.

No gender differences in prognosis and preventive treatment in patients with AMI without significant stenoses.

Objective: To investigate possible gender differences in patients with acute myocardial infarction (AMI) and without significant stenoses on coronary angiography (CAG) regarding prognosis and use of secondary preventive medication.

Design: Nationwide register-based cohort study.

Patients: By compiling data from Danish registries, we identified 20,800 patients hospitalized with AMI during 2005-2007.

The Angio-Seal™ femoral closure device allows immediate ambulation after coronary angiography and percutaneous coronary intervention.

Aims: To test the safety of immediate mobilisation of patients undergoing coronary angiography and percutaneous coronary intervention (PCI) closed with Angio-Seal™ -a femoral vascular closure device.

Methods And Results: First, a randomised controlled trial of immediate mobilisation vs. delayed ambulation was performed followed by a prospective validation registry to test the obtained results in a real-world situation.

Efficacy of post-operative clopidogrel treatment in patients revascularized with coronary artery bypass grafting after myocardial infarction.

Objectives: The objective of this study was to examine the clinical efficacy of clopidogrel treatment on death and recurrent myocardial infarction (MI) among MI patients revascularized by coronary artery bypass graft surgery (CABG).

Background: The benefit from post-operative clopidogrel in CABG-treated MI patients is largely unknown.

Methods: All patients admitted with first-time MI between 2002 and 2006, treated with CABG within 180 days after admission, were identified by nationwide administrative registers.

Influence of distance from home to invasive centre on invasive treatment after acute coronary syndrome: a nationwide study of 24 910 patients.

Objective: To investigate whether distance from a patient's home to the nearest invasive centre influenced the invasive treatment strategy in acute coronary syndrome (ACS).

Methods: This was an observational cohort study using nationwide registries involving 24,910 patients admitted with ACS (median age 67, range 30-90 years). All persons were grouped in tertiles according to the distance from their residence to the invasive centre.

Prognostic information in administrative co-morbidity data following coronary artery bypass grafting.

Objectives: The aim of this study was to evaluate the prognostic information obtainable from administrative data with respect to 30-day mortality following coronary artery bypass grafting (CABG) and to compare it with the European System for Cardiac Operative Risk Evaluation (EuroSCORE) recorded in a clinical database.

Methods: We used a co-morbidity index calculated from administrative data in the Danish National Patient Register by means of all admissions 1 year prior to CABG. In addition, each CABG was categorised as being isolated or not, and acute or not.

Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data.

Background: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens.

Women with acute coronary syndrome are less invasively examined and subsequently less treated than men.

Aims: To investigate if gender bias is present in today's setting of an early invasive strategy for patients with acute coronary syndrome in Denmark (population 5 million).

Methods And Results: We identified all patients admitted to Danish hospitals with acute coronary syndrome in 2005-07 (9561 women and 16 406 men). Cox proportional hazard models were used to estimate the gender differences in coronary angiography (CAG) rate and subsequent revascularization rate within 60 days of admission.

Prognosis in heart failure and the value of {beta}-blockers are altered by the use of antidepressants and depend on the type of antidepressants used.

Background: Depression worsens the prognosis in patients with cardiac disease, and treatment with antidepressants may improve survival. Guidelines recommend use of selective serotonin reuptake inhibitors (SSRIs), but knowledge of the prognostic effect of different classes of antidepressants is sparse.

Methods And Results: We studied 99 335 patients surviving first hospitalization for heart failure (HF) from 1997 to 2005.

[Subacute intracoronary stent thrombosis in a patient with polycythaemia vera].

Polycythaemia vera is a myeloproliferative syndrome with thromboembolic and haemorrhagic complications. We describe a patient with polycythaemia vera and acute coronary syndrome in whom two-vessel intracoronary stent thrombosis occurred a few hours after percutaneous coronary intervention. The case was successfully treated by repeated stenting and abciximab infusion.