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 0.96, 0.88, 0.84, 0.82, 0.85, and 0.78 in women and 0.98, 0.90, 0.89, 0.89, 0.88, and 0.87 in men. Significant predictors of DP were higher age, angina symptoms, higher body mass index, diabetes, smoking, job status, non-marital status in men, lower income, lower educational level, and co-morbidity. Compared with the reference population, probabilities of DP and PEW were significantly increased in all patients with no gender difference (P > 0.2 for interaction). Thus, in pooled multivariable-adjusted analysis, patients referred to CAG for angina had a three-fold higher probability of DP and ~50% higher probability of PEW, with little difference between patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1VD, 2VD, 3VD, the hazard ratios for DP being 2.7, 3.0, 3.3, 3.1, and 3.2 (all P < 0.001) and for PEW being 1.3, 1.4, 1.5, 1.6, and 1.6 (all P < 0.05). CONCLUSION: Patients with angina symptoms and angiographically normal coronary arteries, diffuse non-obstructive CAD, or obstructive CAD at angiography have a three-fold increased probability of DP regardless of angiographic findings.

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. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. CONCLUSION: Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

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. METHODS AND RESULTS: This study included 2073 STEMI patients treated with pPCI. The patients were identified through a hospital register and the Danish National Patient Register. Both registers were also used to establish the diagnosis of HAVB. All-cause mortality was the primary endpoint. During a median follow-up of 2.9 years [interquartile range (IQR) 1.8-4.0] 266 patients died. High-degree atrioventricular block was documented in 67 (3.2%) patients of whom 25 died. Significant independent predictors of HAVB included right coronary artery occlusion, age >65 years, female gender, hypertension, and diabetes. The adjusted mortality rate was significantly increased in patients with HAVB compared to patients without HAVB [hazard ratio = 3.14 (95% confidence interval 2.04-4.84), P< 0.001]. A landmark-analysis 30 days post-STEMI showed equal mortality rates in the two groups. CONCLUSION: The incidence of HAVB in STEMI patients treated with pPCI has been reduced compared with reports from the thrombolytic era. However, despite this improvement high-degree AV block remains a severe prognostic marker in the pPCI era. The mortality rate was only increased within the first 30 days. High-degree atrioventricular block patients who survived beyond this time-point thus had a prognosis equal to patients without HAVB.

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). METHODS: We included 716 consecutive STEMI patients admitted to a single high-volume invasive heart center from September 2006 to December 2008. Endpoints were all-cause mortality, repeat myocardial infarction, admission due to heart failure and combinations thereof. Median follow-up lasted 27 months (interquartile range: 22-33). RESULTS: OPG levels exhibited a non-Gaussian distribution and were therefore divided into quartiles. High levels of OPG were significantly associated with a worse outcome. After adjustment for conventional risk factors (e.g. C-reactive protein, estimated glomerular filtration rate, symptom-to-balloon time and troponin I) using Cox regression, OPG remained a significantly independent predictor of death (HR per increase in OPG quartile: 1.28; CI: 1.03-1.59; p = 0.03), repeat myocardial infarction (HR: 1.30; CI: 1.00-1.68; p = 0.05) and admission with heart failure (HR: 1.50; CI: 1.18-1.90; p = 0.001). CONCLUSION: This study shows that OPG independently predicts long-term outcome in STEMI patients treated with pPCI. Eventually, this knowledge could improve risk stratification and overall outcome.

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. Regional longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured by colour TDI at six mitral annular sites and averaged to provide global estimates. In patients with reversible ischaemia both global systolic and diastolic function were impaired in terms of reduced average s' (5.6 ± 0.9 vs. 6.1 ± 1.1 cm/s; P< 0.05), reduced average e' (5.9 ± 1.8 vs. 7.0 ± 1.7 cm/s; P< 0.01) and increased average E/e' (14.2 ± 5.0 vs. 11.5 ± 3.9; P< 0.01). This impairment of the cardiac function was even more evident in patients with a true-positive SPECT with reduced average s' (5.5 ± 0.8 vs. 6.1 ± 1.1 cm/s; P< 0.01), reduced average e' (5.2 ± 1.5 vs. 7.0 ± 1.7 cm/s; P< 0.001), and increased average E/e' (15.5 ± 5.2 vs. 11.5 ± 3.9; P< 0.001), whereas no difference in myocardial velocities could be demonstrated in patients with a false-positive SPECT compared with controls. CONCLUSION: In patients with stable angina pectoris, preserved ejection fraction, and reversible ischaemia assessed by SPECT, echocardiographic colour TDI performed at rest reveals impaired cardiac function. The impairment of the cardiac function seems to be evident only in patients with a true-positive SPECT and colour TDI may therefore increase its diagnostic value.

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. Significantly less women received CAG (cumulative incidence 64% for women vs. 78% for men, P < 0.05), with a hazard ratio (HR) of 0.68 (95% CI 0.65-0.70, P < 0.0001) compared with men. The difference was narrowed after adjustment for age and comorbidity, but still highly significant (HR 0.82, 95% CI 0.80-0.85, P < 0.0001). Revascularization after CAG was less likely in women with an HR of 0.68 (95% CI 0.66-0.71, P < 0.0001) compared with men. More women (22%) than men (10%) (P < 0.0001) had no significant stenosis on their coronary angiogram. However, after adjustment for the number of significant stenoses, age, and comorbidity women were still less likely to be revascularized (HR 0.91, 95% CI 0.87-0.95, P < 0.0001). CONCLUSION: Women with ACS are approached in a much less aggressively invasive way and receive less interventional treatment than men even after adjusting for differences in comorbidity and number of significant stenoses.

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. METHODS: By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. FINDINGS: During a mean follow-up of 476.5 days (SD 142.0), 1891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 1.33 (95% CI 1.11-1.59) for clopidogrel, 1.23 (0.94-1.61) for vitamin K antagonist, 1.47 (1.28-1.69) for aspirin plus clopidogrel, 1.84 (1.51-2.23) for aspirin plus vitamin K antagonist, 3.52 (2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08-5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18.4%) of 38 960 patients without non-fatal bleeding (HR 3.00, 2.75-3.27, p<0.0001). INTERPRETATION: In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment. FUNDING: Danish Heart Foundation and the Danish Medical Research Council.

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. METHODS: The interim analysis model was designed to reduce the risk of any confidentiality breaches. The Data Access Management Plan comprehensively described the interim analysis operational processes and procedures to maintain the integrity of the ongoing trial while the interim analysis was conducted, submitted, and acted upon by the FDA, and also until completion of the full trial. Most importantly, those who were unblinded to the interim results were limited to a team of 14 members. RESULTS: A total of 150 first major adverse cardiovascular events were recorded at cut-off for the interim analysis. The estimated hazard ratio was 0.92 (95% CI 0.67, 1.27) and non-inferiority to glargine U100 was confirmed as the upper bound of the confidence interval was below 1.8, as prespecified. Based on these results, the FDA approved the use of degludec and degludec/insulin aspart (IDegAsp) in the United States in 2015 before trial completion. CONCLUSIONS: The DEVOTE interim analysis succeeded as a model by which to conduct an interim analysis and submit confidential data for regulatory review and action while continuing the trial to address a primary hypothesis.

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. Individual-level data from national registries were linked to the dedicated EMS database of primary ambulance dispatches supported by physician-manned emergency units. Outcome data were obtained from the Central Population Registry, the National Patient Registry, and the National Registry of Causes of Death. In patients calling the national emergency telephone number, a CV related ambulance alarm code was given in 2,541 patients of 3,410 patients (74.5%) resulting in 2,056 of 3,410 primary CV discharge diagnoses (60.3%) with a 30-day and 5-year all-cause mortality of 24.5% and 46.4%, respectively. Stroke, acute heart failure, and ST-segment elevation myocardial infarction (STEMI) carried a 25- to 50-fold adjusted mortality hazard during the first 4 days. In patients with suspected STEMI, 90.5% had an acute angiography performed. Nontransferred, nonreperfused patients with STEMI (9.1%) carried 80% short-term mortality. Noninvasive management of non-ST-segment elevation myocardial infarction was common (37.9%) and associated with an increased adjusted long-term mortality hazard (hazard ratio 4.17 [2.51 to 8.08], p <0.001). Survival in 447 out-of-hospital cardiac arrest patients (13.1%) was 11.6% at 30 days. In conclusion, patients with a CV ambulance alarm call code and a final CV discharge diagnosis constitute most patients handled by EMS with an extremely elevated short-term mortality hazard and a poor long-term prognosis. Although co-morbidities and frailty may influence triage, this study emphasizes the need for an efficient prehospital phase with focus on CV disease and proper triage of patients suitable for invasive evaluation if the outcomes of acute heart disease are to be improved further in the current international context of hospitals merging into highly specialized entities resulting in longer patient transfers.

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. The study population comprises all patients hospitalised with first-time ACS in Denmark during 2005-2007 (N=24 952). Diabetes was defined as claiming of a prescription for insulin and/or oral hypoglycaemic agents within 6 months prior to the ACS event. Diabetes was present in 2813 (11%) patients. Compared with patients without diabetes, patients with diabetes were older (mean 69 vs 67 years, p<0.0001), less often males (60% vs 64%, p=0.0001) and had more comorbidity. Fewer patients with diabetes underwent CAG: cumulative incidence 64% vs 74% for patients without diabetes, HR=0.72 (95% CI 0.69 to 0.76, p<0.0001); adjusted for age, sex, previous revascularisation and comorbidity HR=0.78 (95% CI 0.74 to 0.82, p<0.0001). More patients with diabetes had CAG showing two-vessel or three-vessel disease (53% vs 38%, p<0.0001). However, revascularisation after CAG revealing multivessel disease was less likely in patients with diabetes (multivariable adjusted HR=0.76, 95% CI 0.68 to 0.85, p<0.0001). CONCLUSIONS: In this nationwide cohort of patients with incident ACS, patients with diabetes were found to be less aggressively managed by an invasive treatment strategy. The factors underlying the decision to defer an invasive strategy in patients with diabetes are unclear and merit further investigation.

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). In recurrent event survival analysis, patients with SAP had 3-4-fold higher risk of hospitalization for CVD irrespective of CAG findings and cardiovascular comorbidity. Multivariable adjusted hazard ratios(95%CI) for patients with angiographically normal coronary arteries was 3.0(2.5-3.5), for angiographically diffuse non-obstructive CAD 3.9(3.3-4.6) and for 1-3-vessel disease 3.6-4.1(range)(all P<0.001). Mean accumulated hospitalization time was 3.5(3.0-4.0)(days/10 years follow-up) in reference individuals and 4.5(3.8-5.2)/7.0(5.4-8.6)/6.7(5.2-8.1)/6.1(5.2-7.4)/8.6(6.6-10.7) in patients with angiographically normal coronary arteries/angiographically diffuse non-obstructive CAD/1-, 2-, and 3-vessel disease, respectively (all P<0.05, age-adjusted). SAP symptoms predicted repeat CAG with multivariable adjusted hazard ratios for patients with angiographically normal coronary arteries being 2.3(1.9-2.9), for angiographically diffuse non-obstructive CAD 5.5(4.4-6.8) and for obstructive CAD 6.6-9.4(range)(all P<0.001). CONCLUSIONS: Patients with SAP symptoms and angiographically normal coronary arteries or angiographically diffuse non-obstructive CAD suffer from considerably greater CVD burdens in terms of hospitalization for CVD and repeat CAG compared with asymptomatic reference individuals even after adjustment for cardiac risk factors and exclusion of cardiovascular comorbidity as cause. Contrary to common perception, excluding obstructive CAD by CAG in such patients does not ensure a benign cardiovascular prognosis.

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. In the pancreas, GLP-1R was predominantly localized in ß-cells with a markedly weaker expression in acinar cells. Pancreatic ductal epithelial cells did not express GLP-1R. In the kidney and lung, GLP-1R was exclusively expressed in smooth muscle cells in the walls of arteries and arterioles. In the heart, GLP-1R was localized in myocytes of the sinoatrial node. In the gastrointestinal tract, the highest GLP-1R expression was seen in the Brunner's gland in the duodenum, with lower level expression in parietal cells and smooth muscle cells in the muscularis externa in the stomach and in myenteric plexus neurons throughout the gut. No GLP-1R was seen in primate liver and thyroid. GLP-1R expression seen with immunohistochemistry was confirmed by functional expression using in situ ligand binding with (125)I-GLP-1. In conclusion, these results give important new insight into the molecular mode of action of GLP-1 analogs by identifying the exact cellular localization of GLP-1R.

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.e., symptoms at least once a month) was present in 64 % of patients with diffuse non-obstructive CAD (1-49 % stenosis), 49 % of patients with normal coronary arteries (0 % stenosis), and 41 % of patients with obstructive CAD (≥ 50 % stenosis) (P = 0.01). Depression and anxiety were more common in patients with persistent angina: 24 versus 7 % (P < 0.001) reported HADS-Depression-scores >7 and 42 versus 21 % (P < 0.001) reported HADS-Anxiety-scores >7. In multivariate regression models, persistent angina was associated with depression (OR 4.3, 95 % confidence interval (CI) 1.9-9.6, P < 0.001), anxiety (OR 2.9, 95 % CI 1.6-5.1, P < 0.001), the severity of persistent angina with impaired physical functioning (P < 0.001), and QOL (P < 0.001); whereas outcomes were not related to age, gender, or degree of CAD. CONCLUSIONS: The study indicates higher prevalence of persistent angina in patients with diffuse non-obstructive CAD or normal coronary arteries than in patients with obstructive CAD. Persistent angina symptoms were associated with long-term anxiety, depression, impaired physical functioning, and QOL irrespective of the degree of CAD. Contrary to common perception, excluding obstructive CAD in stable angina does not ensure a favorable disease course, and further risk stratification and treatment strategies are warranted.

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. Patients were stratified according to weekday- or weekend admissions and four time-periods to investigate for temporal changes. All-cause mortality at 2, 7, 30, and 365 days was investigated using proportional hazards Cox regression. RESULTS: Mortality rates were higher on weekends within seven days of admission in 1997-99 (absolute difference ranging from 0.8 to 1.1%). Weekend-weekday hazard-ratios were 1.13 (1.03-1.23) at day 2 and 1.10 (1.01-1.18) at day 7. There were no significant differences in 2000-09 and estimates suggested an attenuation of the initial 'weekend-effect'. Overall, the use of coronary angiography (34.9% vs. 72.3%) and percutaneous coronary intervention (6.6% vs. 51.0%) within 30 days increased, as did the use of statins (49.9% vs. 80.1%.) and clopidogrel (26.7% vs. 72.7%). The cumulative mortality decreased during the study period from 5.4% to 2.5% at day of admission, from 19.5% to 11.0% at day 30 and from 28.0% to 19.0% at day 365 (all tests for trend p<0.0001). CONCLUSIONS: No persistent 'weekend-effect' on mortality was present in patients with AMI in 1997-2009. Overall, mortality rates have decreased concomitantly with an increased use of current guideline-recommended invasive and medical therapy.

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 (≥ 3.0mm) were randomised 2:1 to DES or BMS. In an a priori planned secondary analysis, outcomes were evaluated according to renal function defined by estimated glomerular filtration rates (eGFR; normal: eGFR ≥ 60 ml/min/1.73 m(2); CKD: eGFR<60 ml/min/1.73 m(2)). The primary endpoint was the first major adverse cardiac event (MACE: cardiac death, myocardial infarction, target vessel revascularisation) up to 2 years. A Cox proportional-hazard model was used to evaluate adjusted relative risks (hazard rates, HRs) for BMS versus DES. The interaction of stent type and renal function was tested. CKD patients (189 (11.2%)/1681 with such data) had a 2-year MACE rate of 8.5% versus 7.4% in those without CKD [HR 0.98 (0.56-1.72), p=0.95] with cardiac mortalities of 5.3% and 1.5%, respectively (p=0.002, non-significant after baseline adjustments). The MACE rate was lower in CKD patients with DES than with BMS [4.9% versus 15.2%, p=0.017, HR 0.29(0.10-0.80)] as was the MACE rate in patients without CKD [5.6% with DES versus 11.1% with BMS, p<0.0001, HR 0.51(0.35-0.75)]. No significant interaction between stent type and renal function was found. CONCLUSIONS: This analysis of patients needing large coronary artery stenting confirms the increased mortality of CKD patients and documents a long-term benefit of DES compared to BMS irrespective of kidney function.

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. We included the 834 women and 761 men without significant stenoses on CAG who were discharged and alive after 60 days. MAIN OUTCOME MEASURES: All-cause mortality, recurrent AMI, and redeeming a prescription for a lipid-lowering drug, beta-blocker, clopidogrel, or aspirin within 60 days of discharge. RESULTS: During follow-up, 97 women and 60 men died, resulting in a crude female/male hazard ratio (HR) of 1.51 (95% CI 1.09-2.08). After adjustment for age, time-period, and comorbidity, the gender difference was attenuated (HR 1.22, 95% CI 0.86-1.72). AMI recurrence was experienced by 28 women and 29 men with a female/male HR 0.88 (95% CI 0.52-1.48). After multivariable adjustment results were similar (HR 0.84, 95% CI 0.50-1.43). More women than men redeemed a prescription for lipid-lowering drugs with no differences in other medication. In the adjusted models lipid-lowering drugs, beta-blockers, clopidogrel, and aspirin were all redeemed equally with odds ratio (OR) 1.25 (95% CI 0.99-1.59), OR 1.10 (95% CI 0.88-1.37), OR 1.09 (95% CI 0.88-1.34), and OR 1.13 (95% CI 0.90-1.42), respectively. CONCLUSION: Our study shows that in a population of patients with a first admission for AMI and no significant stenoses on CAG, women share the same prospects as men regarding long-term prognosis and the extent of secondary preventive medical treatment.

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. The PPCI center registry was linked by person identification number to emergency medical services (EMS) and National Board of Health databases in the period of 2005-2008. Patients were stratified according to transfer distances to PPCI into zone 1 (0-25 km), zone 2 (65-100 km) and zone 3 (101-185 km) and according to referral by pre-hospital triage. System delay was 86 minutes (interquartile range (IQR) 72-113) in zone 1, 133 (116-180) in zone 2 and 173 (145-215) in zone 3 (p<0.001). PCI-related delay in directly referred patients was 109 (92-121) minutes in zone 2, but exceeded recommendations in zone 3 (139 (121-160)) and for patients admitted via the local hospital (219 (171-250)). System delay was an independent predictor of mortality (p<0.001). CONCLUSIONS: Pre-hospital triage is feasible in 73% of patients. PCI-related delay exceeded European Society of Cardiology (ESC) guidelines for patients living >100 km away and for non-directly referred patients. Sorting the PPCI centers catchment area into geographical zones identifies patients with long reperfusion delays. Possible solutions are pharmaco-invasive regiments, research in early ischemia detection, airborne transfer and EMS personnel education that ensures pre-hospital triage.

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. PATIENTS: We included 18,279 patients: 6364 women (35%) and 11,915 men (65%), admitted with AMI (median age, 67 years; range, 30-90 years) surviving for at least 2 months. INTERVENTIONS: According to sex, patients were stratified by invasive treatment strategy: (1) revascularized; (2) examined with coronary angiography (CAG) but not revascularized; and (3) not examined with CAG. MAIN OUTCOME MEASURES: All-cause mortality and readmission with AMI. Initiation of secondary preventive medication. RESULTS: Of 18,279 patients with a first AMI who survived 2 months, 1857 women (29%) and 1756 men (15%) were not examined with CAG (P<.001), 1295 women (20%) and 1563 men (13%) were examined but not revascularized (P<.001), and 3212 women (51%) and 8596 men (72%) were revascularized (P<.001). Not being examined with CAG after AMI was associated with a three-fold increase in risk of death and, importantly, a 50% increase in the risk of a recurrent AMI compared with patients who were revascularized. Among patients who were revascularized, 85-92% initiated recommended secondary preventive medication compared to 46-71% in patients not examined with CAG (P<.001). Initiation of secondary preventive medication was higher in men (81-84%) than in women (73-79%; P<.001), which could be ascribed to the differences in invasive strategy. CONCLUSIONS: In both sexes, those who were not examined had a highly increased risk of both recurrent AMI and death. Moreover, initiation of secondary preventive medication was closely related to the choice of invasive strategy disfavoring the women.

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. The randomised trial comprised 300 patients; the validation registry comprised 1,097 patients. Primary endpoints were complications defined as: small haematoma <5 cm and/or minor bleeding/oozing from the puncture site, haematomas ≥ 5 cm, bleeding needing transfusion, bleeding needing surgical attention, pseudoaneurysm and vasovagal reaction. In the randomised trial, overall complications were similar in both groups (16.0%vs.18.8%; p=0.53). Small haematomas/small bleedings/oozing were the most frequent (12.2% vs.15.3; p=0.44). There were no bleedings needing transfusion or surgical attention, and no pseudoaneurysms occurred. The prospective registry showed similar results. In the standard-care cohort, complications were similar to those in the implementation cohort (9.6% vs.11.3%; p=0.41), mainly consisting of small haematomas/minor bleedings/oozing (6.1% vs.7.3%; p=0.49). No bleedings needed transfusion or surgical attention. Pseudoaneurysms occurred in 1 (0.34%) vs. 3 (0.37%; p=0.94) and vasovagal reactions in three (1.0%) vs. four (0.5%; p=0.33) patients. It was possible to mobilise 87% of patients in the implementation cohort. CONCLUSIONS: In patients undergoing coronary angiography or PCI, the use of immediate mobilisation after Angio-Seal™ deployment is safe. With routine use of a femoral vascular closure device, approximately 87% of patients are suitable for immediate mobilisation.

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. Cox proportional hazard models were applied to estimate the differences in coronary angiography and revascularisation rate within 60 days of admission according to the distance to the centre. The end points were coronary angiography and subsequent revascularisation. RESULTS: Of 24,910 patients with a first ACS, 33% resided <21 km from one of the five invasive centres in Denmark, 33% lived between 21 and 64 km away and 34% lived >64 km away. The incidence of coronary angiography was 68% for long distance versus 77% for short distance (p<0.05), with an HR of 0.78 (95% CI 0.75 to 0.81, p<0.0001). Adjustment for patient characteristics such as age, sex, co-morbidity and socioeconomic status did not attenuate the difference (HR 0.74, 95% CI 0.71 to 0.77, p<0.0001). Furthermore, revascularisation in the subgroup examined with coronary angiography was less likely for those residing a long distance from the invasive centre compared with those living nearer (adjusted HR of 0.82 (95% CI 0.78 to 0.85, p<0.0001). CONCLUSIONS: In patients hospitalised with ACS, invasive examination and treatment were less likely the further away from an invasive centre the patients resided, thus equal and uniform invasive examination and treatment was not found.