Søren Galatius - Academia.edu (original) (raw)

Papers by Søren Galatius

Research paper thumbnail of Long‐Term Results After Drug‐Eluting Versus Bare‐Metal Stent Implantation in Saphenous Vein Grafts: Randomized Controlled Trial

Journal of the American Heart Association, 2020

Background Efficacy data on drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous... more Background Efficacy data on drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous vein grafts are controversial. We aimed to compare DES with BMS among patients undergoing saphenous vein grafts intervention regarding long‐term outcome. Methods and Results In this multinational trial, patients were randomized to paclitaxel‐eluting or BMS. The primary end point was major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target‐vessel revascularization at 1 year. Secondary end points included major adverse cardiac events and its individual components at 5‐year follow‐up. One hundred seventy‐three patients were included in the trial (89 DES versus 84 BMS). One‐year major adverse cardiac event rates were lower in DES compared with BMS (2.2% versus 16.0%, hazard ratio, 0.14; 95% CI, 0.03–0.64, P =0.01), which was mainly driven by a reduction of subsequent myocardial infarctions and need for target‐vessel revascularization. Five‐year major adverse c...

Research paper thumbnail of Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial

BMJ Open, 2021

Introduction Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no ob... more Introduction Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. Methods and analysis FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the p...

Research paper thumbnail of expansion in compensated heart failure Neuroendocrine and renal effects of intravascular volume

Research paper thumbnail of Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II

Research paper thumbnail of Echocardiography improves prediction of major adverse cardiovascular events in a population with type 1 diabetes and without known heart disease: the Thousand 1 Study

Diabetologia, 2019

Aims/hypothesis Cardiovascular disease is the most common comorbidity in type 1 diabetes. However... more Aims/hypothesis Cardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease. Methods A prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental prognostic value when added to the clinical Steno T1D Risk Engine were examined. Results A total of 1093 individuals were included: median (interquartile range) age 50.2 (39.2-60.3) years and HbA 1c 65 (56-74) mmol/mol; 53% men; and mean (SD) BMI 25.5 (3.9) kg/m 2 and diabetes duration 25.8 (14.6) years. During 7.5 years of followup, 145 (13.3%) experienced MACE. Echocardiography significantly and independently predicted MACE: left ventricular ejection fraction (LVEF) <45% (n = 18) vs ≥45% (n = 1075), HR (95% CI) 3.93 (1.91, 8.08), p < 0.001; impaired global longitudinal strain (GLS), 1.65 (1.17, 2.34) (n = 263), p = 0.005; diastolic mitral early velocity (E)/early diastolic tissue Doppler velocity (e′) <8 (n = 723) vs E/e′ 8-12 (n = 285), 1.59 (1.04, 2.42), p = 0.031; and E/e′ <8 vs E/e′ ≥12 (n = 85), 2.30 (1.33, 3.97), p = 0.003. In individuals with preserved LVEF (n = 1075), estimates for impaired GLS were 1.49 (1.04, 2.15), p = 0.032; E/e′ <8 vs E/e′ 8-12, 1.61 (1.04, 2.49), p = 0.033; and E/e′ <8 vs E/e′ ≥12, 2.49 (1.41, 4.37), p = 0.001. Adding echocardiographic variables to the Steno T1D Risk Engine significantly improved risk prediction: Harrell's C statistic, 0.791 (0.757, 0.824) vs 0.780 (0.746, 0.815), p = 0.027; and net reclassification index, 52%, p < 0.001. Conclusions/interpretation In individuals with type 1 diabetes without known heart disease, echocardiography significantly improves risk prediction over and above guideline-recommended clinical risk factors alone and could have a role in clinical care.

Research paper thumbnail of Calf blood flow during prolonged tilt in idiopathic dilated cardiomyopathy and after cardiac transplantation

American Journal of Physiology-Heart and Circulatory Physiology, 2000

In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief... more In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief head-up tilt that appears to normalize after transplantation (HTX) may be present during prolonged observation also. Therefore, we studied the effect of prolonged (30 min) 50° head-up tilt on calf skeletal muscle blood flow measured by the local133Xe washout method in CHF and after HTX and in patients with the presence vs. absence of native right atrium (+PNA and −PNA, respectively). During brief head-up tilt, skeletal muscle blood flow increased 13 ± 42% in 9 severe CHF patients in contrast to a −28 ± 22% decrease ( P < 0.01) in 11 control subjects, −24 ± 30% decrease in 15 moderate CHF patients ( P < 0.05), −25 ± 14% decrease in 12 patients with recent HTX ( P < 0.01), and −21 ± 24% decrease in 8 patients with distant HTX ( P = 0.06). However, during sustained tilt, blood flow declined to similar levels of that in the other groups in severe CHF. HTX −PNA vs. +PNA showed blunt...

Research paper thumbnail of Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

Circulation, 2018

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in pa... more Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combinati...

Research paper thumbnail of Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Lancet (London, England), 2018

Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and i... more Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30-50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be ...

Research paper thumbnail of Effects of Body Mass Index on Clinical Outcomes in Female Patients Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: Results From a Patient-Level Pooled Analysis of Randomized Controlled Trials

JACC. Cardiovascular interventions, Jan 8, 2018

This study sought to investigate the effect of different body mass index (BMI) categories on clin... more This study sought to investigate the effect of different body mass index (BMI) categories on clinical outcomes in female patients treated with percutaneous coronary intervention (PCI) and drug-eluting stents. Patients with higher BMI might, paradoxically, have better long-term clinical outcomes after acute coronary syndrome treated with PCI. We pooled patient-level data for female participants from 26 randomized trials on PCI with drug-eluting stents. Patients were stratified into underweight (BMI, <18.5), normoweight (BMI, 18.5 to 24.9), overweight (BMI, 25 to 29.9), obese (BMI, 30 to 34.9), or morbidly obese (BMI, ≥35). The primary endpoint was major adverse cardiac events, a composite of death, myocardial infarction, or target lesion revascularization at 3 years. Among 11,557 female patients included in the pooled database, 9,420 were treated with a drug-eluting stent and had BMI data available. Patients with higher BMI were significantly younger and with more cardiovascular r...

Research paper thumbnail of Effect of Increasing Stent Length on 3-Year Clinical Outcomes in Women Undergoing Percutaneous Coronary Intervention With New-Generation Drug-Eluting Stents: Patient-Level Pooled Analysis of Randomized Trials From the WIN-DES Initiative

JACC. Cardiovascular interventions, Jan 8, 2018

The aim of this study was to examine whether stent length per patient and stent length per lesion... more The aim of this study was to examine whether stent length per patient and stent length per lesion are negative markers for 3-year outcomes in women following percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES). In the era of advanced stent technologies, whether stent length remains a correlate of adverse outcomes is unclear. Women treated with new-generation DES in 14 randomized trials from the WIN-DES (Women in Innovation and Drug-Eluting Stents) pooled database were evaluated. Total stent length per patient, which was available in 5,403 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 24 mm; quartile 3, 24 to 36 mm; quartile 4, ≥36 mm), and stent length per lesion, which was available in 5,232 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 20 mm; quartile 3, 20 to 27 mm; quartile 4, ≥27 mm) were analyzed in quartiles. The primary endpoint was 3-year major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardia...

Research paper thumbnail of Contemporary evaluation of patients suspected of stable angina - diagnostic expenditure vs. final diagnosis. Results from a large unselected hospital patient sample

European heart journal. Quality of care & clinical outcomes, Jan 18, 2017

Stable angina is the most common presentation of heart disease and has a good prognosis. With dec... more Stable angina is the most common presentation of heart disease and has a good prognosis. With declining coronary artery disease (CAD), rates a diagnostic approach balancing costs and benefits is a challenge, particularly in women. This study describes the real-life diagnostic workup in a large hospital to explore whether the diagnostic approach may be improved.

Research paper thumbnail of Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery: An analysis of the BASKET-PROVE I and II trials

Catheterization and Cardiovascular Interventions, 2017

Research paper thumbnail of Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents: Comparative cost-effectiveness analysis from the BASKET-PROVE cohorts

International Journal of Cardiology, 2017

, Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndrom... more , Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents: Comparative cost-effectiveness analysis from the BASKET-PROVE cohorts, International

Research paper thumbnail of Applied mediation analyses - a review and tutorial

Epidemiology and Health, 2017

In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways... more In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation in the R package medflex. All results are illustrated using a recent study on the causal pathways stemming from the early invasive treatment of acute coronary syndrome, for which the rich Danish population registers allow us to follow patients' medication use and more after being discharged from hospital.

Research paper thumbnail of Long-term Safety and Efficacy of New-Generation Drug-Eluting Stents in Women With Acute Myocardial Infarction: From the Women in Innovation and Drug-Eluting Stents (WIN-DES) Collaboration

JAMA cardiology, Jan 28, 2017

Women with acute myocardial infarction (MI) undergoing mechanical reperfusion remain at increased... more Women with acute myocardial infarction (MI) undergoing mechanical reperfusion remain at increased risk of adverse cardiac events and mortality compared with their male counterparts. Whether the benefits of new-generation drug-eluting stents (DES) are preserved in women with acute MI remains unclear. To investigate the long-term safety and efficacy of new-generation DES vs early-generation DES in women with acute MI. Collaborative, international, individual patient-level data of women enrolled in 26 randomized clinical trials of DES were analyzed between July and December 2016. Only women presenting with an acute coronary syndrome were included. Study population was categorized according to presentation with unstable angina (UA) vs acute MI. Acute MI included non-ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). Randomization to early- (sirolimus- or paclitaxel-eluting stents) vs new-generation (everolimus-, zotarolimus-, or biolimus-eluting stents) DES. Composite ...

Research paper thumbnail of Impact of stent diameter and length on in-stent restenosis after DES vs BMS implantation in patients needing large coronary stents-A clinical and health-economic evaluation

Cardiovascular Therapeutics, 2016

Aims: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use dr... more Aims: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug-eluting stents (DES) instead of bare-metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis (ISR) in the BASKET-PROVE study population and evaluated the cost-effectiveness of DES compared to BMS. Methods/Results: The BASKET-PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves with regard to quality-adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective. Conclusion: In the BASKET-PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length.

Research paper thumbnail of Frequency of Cardiac Death and Stent Thrombosis in Patients with Chronic Obstructive Pulmonary Disease Undergoing Percutaneous Coronary Intervention (From the BASKET-PROVE I and II Trials)

The American Journal of Cardiology, 2017

Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death followi... more Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death following percutaneous coronary intervention (PCI) with bare-metal stents (BMS). Regarding other outcomes previous studies have shown conflicting results and the impact of drug-eluting stent (DES) in this population is not well known. We analyzed 4605 patients that underwent PCI with BMS (33.1%) or DES (66.9%) from the BASKET-PROVE trials I and II. COPD patients (n=283, 6.1%), were older and had more frequently a smoking or cardiovascular event history. At 2-year follow-up, cumulative event rates for patients with versus without COPD were the following: major adverse cardiac events [MACE: composite of cardiac death, non-fatal myocardial infarction and target vessel revascularization]: 15.2 vs. 8.1% (p<0.001); all-cause death: 11.7 vs. 2.4%, (p<0.001); cardiac death: 5.7 vs. 1.2%, (p<0.001); myocardial infarction: 3.5 vs. 1.9% (p=0.045); definite/probable/possible stent thrombosis: 2.5 vs. 0.9% (p=0.01); and major bleeding: 4.2 vs. 2.1% (p=0.014). After adjusting for confounders including smoking status, COPD remained an independent predictor for MACE (HR 1.80, 95%CI 1.31-2.49), allcause death (HR 3.62, 95%CI 2.41-5.45), cardiac death (HR 3.12, 95%CI 1.74-5.60) and stent thrombosis (HR 2.39, 95% CI 1.03-5.54). We did not find evidence of an interaction between COPD and DES implantation (P for interaction = 0.29) for MACE. In conclusion, COPD is associated with increased 2-year rates of all-cause death, cardiac death and stent thrombosis after stent implantation. DES use appears to be beneficial also in COPD patients.

Research paper thumbnail of Suvival benefit with 12 versus 6-months dual antiplatelet therapy after coronary stent implantation: a report from BASKET and BASKET-PROVE

European Heart Journal, 2013

, of which 18 patients with cardiopulmonary arrest on arrival were excluded and 642 patients were... more , of which 18 patients with cardiopulmonary arrest on arrival were excluded and 642 patients were investigated retrospectively. Results: The 642 patients consisted of 493 male and 149 female patients, the average age 69.9±11.4 years and follow up period 441.6±315.9 days. Coexisting AF was seen in 77 (12.0%) patients, of which 49 were paroxysmal AF and 28 were persistent/ chronic AF.The rate of AF group was significantly higher than that of non-AF group in mortality (14.3% vs. 6.9%, P=0.038) and hemorrhagic events (19.5% vs. 6.9%,P=0.001). Multivariate analysis showed the AF was an independent prognostic marker on mortality (OR2.3, 95% CI1.1-4.8,P=0.032) and hemorrhage (OR2.1, 95% CI1.1-4.3,P=0.035), events from age, diabetes, chronic kidney disease and hyperlipidemia. The incidence of thromboembolic events were similar in the both groups (3.1% vs 3.1%,P=1.00).Comparing paroxysmal AF and persistent/chronic AF, mortality and rate of hemorrhage events was more common in paroxysmal AF group than persistent/chronic AF (mortality 16.3% vs. 10.7%, hemorrhage events 22.4% vs 14.2%). On the other hand, triple therapy (oral anticoagulant with aspirin and clopidogrel or ticropidine) were performed in 63 (81.8%) patients with AF, and dual antiplatelet therapy (DAPT: aspirin and clopidogrel or ticropidine) were performed in 14 (18.2%). Mortality rate of the triple antiplatelet therapy group was higher than that of the DAPT group (15.9%vs 7.1%) and hemorrhage events (20.6% vs 14.3%). Conclusion: Hemorrhage events and mortality were more common in patients with AF after PCI. Triple therapy was found to reduce thromboembolic events; however, its usage may have more harmful influences than the severity of AF regarding mortality and the hemorrhage events.

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

Open heart, 2015

Guidelines recommend an early invasive strategy for patients with diabetes with acute coronary sy... more 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. 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, ...

Research paper thumbnail of No gender differences in prognosis and preventive treatment in patients with AMI without significant stenoses

European journal of preventive cardiology, 2012

To investigate possible gender differences in patients with acute myocardial infarction (AMI) and... more 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. Nationwide register-based cohort study. 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. All-cause mortality, recurrent AMI, and redeeming a prescription for a lipid-lowering drug, beta-blocker, clopidogrel, or aspirin within 60 days of discharge. 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). ...

Research paper thumbnail of Long‐Term Results After Drug‐Eluting Versus Bare‐Metal Stent Implantation in Saphenous Vein Grafts: Randomized Controlled Trial

Journal of the American Heart Association, 2020

Background Efficacy data on drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous... more Background Efficacy data on drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous vein grafts are controversial. We aimed to compare DES with BMS among patients undergoing saphenous vein grafts intervention regarding long‐term outcome. Methods and Results In this multinational trial, patients were randomized to paclitaxel‐eluting or BMS. The primary end point was major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target‐vessel revascularization at 1 year. Secondary end points included major adverse cardiac events and its individual components at 5‐year follow‐up. One hundred seventy‐three patients were included in the trial (89 DES versus 84 BMS). One‐year major adverse cardiac event rates were lower in DES compared with BMS (2.2% versus 16.0%, hazard ratio, 0.14; 95% CI, 0.03–0.64, P =0.01), which was mainly driven by a reduction of subsequent myocardial infarctions and need for target‐vessel revascularization. Five‐year major adverse c...

Research paper thumbnail of Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial

BMJ Open, 2021

Introduction Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no ob... more Introduction Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. Methods and analysis FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the p...

Research paper thumbnail of expansion in compensated heart failure Neuroendocrine and renal effects of intravascular volume

Research paper thumbnail of Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II

Research paper thumbnail of Echocardiography improves prediction of major adverse cardiovascular events in a population with type 1 diabetes and without known heart disease: the Thousand 1 Study

Diabetologia, 2019

Aims/hypothesis Cardiovascular disease is the most common comorbidity in type 1 diabetes. However... more Aims/hypothesis Cardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease. Methods A prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental prognostic value when added to the clinical Steno T1D Risk Engine were examined. Results A total of 1093 individuals were included: median (interquartile range) age 50.2 (39.2-60.3) years and HbA 1c 65 (56-74) mmol/mol; 53% men; and mean (SD) BMI 25.5 (3.9) kg/m 2 and diabetes duration 25.8 (14.6) years. During 7.5 years of followup, 145 (13.3%) experienced MACE. Echocardiography significantly and independently predicted MACE: left ventricular ejection fraction (LVEF) <45% (n = 18) vs ≥45% (n = 1075), HR (95% CI) 3.93 (1.91, 8.08), p < 0.001; impaired global longitudinal strain (GLS), 1.65 (1.17, 2.34) (n = 263), p = 0.005; diastolic mitral early velocity (E)/early diastolic tissue Doppler velocity (e′) <8 (n = 723) vs E/e′ 8-12 (n = 285), 1.59 (1.04, 2.42), p = 0.031; and E/e′ <8 vs E/e′ ≥12 (n = 85), 2.30 (1.33, 3.97), p = 0.003. In individuals with preserved LVEF (n = 1075), estimates for impaired GLS were 1.49 (1.04, 2.15), p = 0.032; E/e′ <8 vs E/e′ 8-12, 1.61 (1.04, 2.49), p = 0.033; and E/e′ <8 vs E/e′ ≥12, 2.49 (1.41, 4.37), p = 0.001. Adding echocardiographic variables to the Steno T1D Risk Engine significantly improved risk prediction: Harrell's C statistic, 0.791 (0.757, 0.824) vs 0.780 (0.746, 0.815), p = 0.027; and net reclassification index, 52%, p < 0.001. Conclusions/interpretation In individuals with type 1 diabetes without known heart disease, echocardiography significantly improves risk prediction over and above guideline-recommended clinical risk factors alone and could have a role in clinical care.

Research paper thumbnail of Calf blood flow during prolonged tilt in idiopathic dilated cardiomyopathy and after cardiac transplantation

American Journal of Physiology-Heart and Circulatory Physiology, 2000

In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief... more In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief head-up tilt that appears to normalize after transplantation (HTX) may be present during prolonged observation also. Therefore, we studied the effect of prolonged (30 min) 50° head-up tilt on calf skeletal muscle blood flow measured by the local133Xe washout method in CHF and after HTX and in patients with the presence vs. absence of native right atrium (+PNA and −PNA, respectively). During brief head-up tilt, skeletal muscle blood flow increased 13 ± 42% in 9 severe CHF patients in contrast to a −28 ± 22% decrease ( P < 0.01) in 11 control subjects, −24 ± 30% decrease in 15 moderate CHF patients ( P < 0.05), −25 ± 14% decrease in 12 patients with recent HTX ( P < 0.01), and −21 ± 24% decrease in 8 patients with distant HTX ( P = 0.06). However, during sustained tilt, blood flow declined to similar levels of that in the other groups in severe CHF. HTX −PNA vs. +PNA showed blunt...

Research paper thumbnail of Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

Circulation, 2018

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in pa... more Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combinati...

Research paper thumbnail of Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Lancet (London, England), 2018

Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and i... more Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30-50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be ...

Research paper thumbnail of Effects of Body Mass Index on Clinical Outcomes in Female Patients Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: Results From a Patient-Level Pooled Analysis of Randomized Controlled Trials

JACC. Cardiovascular interventions, Jan 8, 2018

This study sought to investigate the effect of different body mass index (BMI) categories on clin... more This study sought to investigate the effect of different body mass index (BMI) categories on clinical outcomes in female patients treated with percutaneous coronary intervention (PCI) and drug-eluting stents. Patients with higher BMI might, paradoxically, have better long-term clinical outcomes after acute coronary syndrome treated with PCI. We pooled patient-level data for female participants from 26 randomized trials on PCI with drug-eluting stents. Patients were stratified into underweight (BMI, <18.5), normoweight (BMI, 18.5 to 24.9), overweight (BMI, 25 to 29.9), obese (BMI, 30 to 34.9), or morbidly obese (BMI, ≥35). The primary endpoint was major adverse cardiac events, a composite of death, myocardial infarction, or target lesion revascularization at 3 years. Among 11,557 female patients included in the pooled database, 9,420 were treated with a drug-eluting stent and had BMI data available. Patients with higher BMI were significantly younger and with more cardiovascular r...

Research paper thumbnail of Effect of Increasing Stent Length on 3-Year Clinical Outcomes in Women Undergoing Percutaneous Coronary Intervention With New-Generation Drug-Eluting Stents: Patient-Level Pooled Analysis of Randomized Trials From the WIN-DES Initiative

JACC. Cardiovascular interventions, Jan 8, 2018

The aim of this study was to examine whether stent length per patient and stent length per lesion... more The aim of this study was to examine whether stent length per patient and stent length per lesion are negative markers for 3-year outcomes in women following percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES). In the era of advanced stent technologies, whether stent length remains a correlate of adverse outcomes is unclear. Women treated with new-generation DES in 14 randomized trials from the WIN-DES (Women in Innovation and Drug-Eluting Stents) pooled database were evaluated. Total stent length per patient, which was available in 5,403 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 24 mm; quartile 3, 24 to 36 mm; quartile 4, ≥36 mm), and stent length per lesion, which was available in 5,232 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 20 mm; quartile 3, 20 to 27 mm; quartile 4, ≥27 mm) were analyzed in quartiles. The primary endpoint was 3-year major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardia...

Research paper thumbnail of Contemporary evaluation of patients suspected of stable angina - diagnostic expenditure vs. final diagnosis. Results from a large unselected hospital patient sample

European heart journal. Quality of care & clinical outcomes, Jan 18, 2017

Stable angina is the most common presentation of heart disease and has a good prognosis. With dec... more Stable angina is the most common presentation of heart disease and has a good prognosis. With declining coronary artery disease (CAD), rates a diagnostic approach balancing costs and benefits is a challenge, particularly in women. This study describes the real-life diagnostic workup in a large hospital to explore whether the diagnostic approach may be improved.

Research paper thumbnail of Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery: An analysis of the BASKET-PROVE I and II trials

Catheterization and Cardiovascular Interventions, 2017

Research paper thumbnail of Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents: Comparative cost-effectiveness analysis from the BASKET-PROVE cohorts

International Journal of Cardiology, 2017

, Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndrom... more , Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents: Comparative cost-effectiveness analysis from the BASKET-PROVE cohorts, International

Research paper thumbnail of Applied mediation analyses - a review and tutorial

Epidemiology and Health, 2017

In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways... more In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation in the R package medflex. All results are illustrated using a recent study on the causal pathways stemming from the early invasive treatment of acute coronary syndrome, for which the rich Danish population registers allow us to follow patients' medication use and more after being discharged from hospital.

Research paper thumbnail of Long-term Safety and Efficacy of New-Generation Drug-Eluting Stents in Women With Acute Myocardial Infarction: From the Women in Innovation and Drug-Eluting Stents (WIN-DES) Collaboration

JAMA cardiology, Jan 28, 2017

Women with acute myocardial infarction (MI) undergoing mechanical reperfusion remain at increased... more Women with acute myocardial infarction (MI) undergoing mechanical reperfusion remain at increased risk of adverse cardiac events and mortality compared with their male counterparts. Whether the benefits of new-generation drug-eluting stents (DES) are preserved in women with acute MI remains unclear. To investigate the long-term safety and efficacy of new-generation DES vs early-generation DES in women with acute MI. Collaborative, international, individual patient-level data of women enrolled in 26 randomized clinical trials of DES were analyzed between July and December 2016. Only women presenting with an acute coronary syndrome were included. Study population was categorized according to presentation with unstable angina (UA) vs acute MI. Acute MI included non-ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). Randomization to early- (sirolimus- or paclitaxel-eluting stents) vs new-generation (everolimus-, zotarolimus-, or biolimus-eluting stents) DES. Composite ...

Research paper thumbnail of Impact of stent diameter and length on in-stent restenosis after DES vs BMS implantation in patients needing large coronary stents-A clinical and health-economic evaluation

Cardiovascular Therapeutics, 2016

Aims: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use dr... more Aims: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug-eluting stents (DES) instead of bare-metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis (ISR) in the BASKET-PROVE study population and evaluated the cost-effectiveness of DES compared to BMS. Methods/Results: The BASKET-PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves with regard to quality-adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective. Conclusion: In the BASKET-PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length.

Research paper thumbnail of Frequency of Cardiac Death and Stent Thrombosis in Patients with Chronic Obstructive Pulmonary Disease Undergoing Percutaneous Coronary Intervention (From the BASKET-PROVE I and II Trials)

The American Journal of Cardiology, 2017

Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death followi... more Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death following percutaneous coronary intervention (PCI) with bare-metal stents (BMS). Regarding other outcomes previous studies have shown conflicting results and the impact of drug-eluting stent (DES) in this population is not well known. We analyzed 4605 patients that underwent PCI with BMS (33.1%) or DES (66.9%) from the BASKET-PROVE trials I and II. COPD patients (n=283, 6.1%), were older and had more frequently a smoking or cardiovascular event history. At 2-year follow-up, cumulative event rates for patients with versus without COPD were the following: major adverse cardiac events [MACE: composite of cardiac death, non-fatal myocardial infarction and target vessel revascularization]: 15.2 vs. 8.1% (p<0.001); all-cause death: 11.7 vs. 2.4%, (p<0.001); cardiac death: 5.7 vs. 1.2%, (p<0.001); myocardial infarction: 3.5 vs. 1.9% (p=0.045); definite/probable/possible stent thrombosis: 2.5 vs. 0.9% (p=0.01); and major bleeding: 4.2 vs. 2.1% (p=0.014). After adjusting for confounders including smoking status, COPD remained an independent predictor for MACE (HR 1.80, 95%CI 1.31-2.49), allcause death (HR 3.62, 95%CI 2.41-5.45), cardiac death (HR 3.12, 95%CI 1.74-5.60) and stent thrombosis (HR 2.39, 95% CI 1.03-5.54). We did not find evidence of an interaction between COPD and DES implantation (P for interaction = 0.29) for MACE. In conclusion, COPD is associated with increased 2-year rates of all-cause death, cardiac death and stent thrombosis after stent implantation. DES use appears to be beneficial also in COPD patients.

Research paper thumbnail of Suvival benefit with 12 versus 6-months dual antiplatelet therapy after coronary stent implantation: a report from BASKET and BASKET-PROVE

European Heart Journal, 2013

, of which 18 patients with cardiopulmonary arrest on arrival were excluded and 642 patients were... more , of which 18 patients with cardiopulmonary arrest on arrival were excluded and 642 patients were investigated retrospectively. Results: The 642 patients consisted of 493 male and 149 female patients, the average age 69.9±11.4 years and follow up period 441.6±315.9 days. Coexisting AF was seen in 77 (12.0%) patients, of which 49 were paroxysmal AF and 28 were persistent/ chronic AF.The rate of AF group was significantly higher than that of non-AF group in mortality (14.3% vs. 6.9%, P=0.038) and hemorrhagic events (19.5% vs. 6.9%,P=0.001). Multivariate analysis showed the AF was an independent prognostic marker on mortality (OR2.3, 95% CI1.1-4.8,P=0.032) and hemorrhage (OR2.1, 95% CI1.1-4.3,P=0.035), events from age, diabetes, chronic kidney disease and hyperlipidemia. The incidence of thromboembolic events were similar in the both groups (3.1% vs 3.1%,P=1.00).Comparing paroxysmal AF and persistent/chronic AF, mortality and rate of hemorrhage events was more common in paroxysmal AF group than persistent/chronic AF (mortality 16.3% vs. 10.7%, hemorrhage events 22.4% vs 14.2%). On the other hand, triple therapy (oral anticoagulant with aspirin and clopidogrel or ticropidine) were performed in 63 (81.8%) patients with AF, and dual antiplatelet therapy (DAPT: aspirin and clopidogrel or ticropidine) were performed in 14 (18.2%). Mortality rate of the triple antiplatelet therapy group was higher than that of the DAPT group (15.9%vs 7.1%) and hemorrhage events (20.6% vs 14.3%). Conclusion: Hemorrhage events and mortality were more common in patients with AF after PCI. Triple therapy was found to reduce thromboembolic events; however, its usage may have more harmful influences than the severity of AF regarding mortality and the hemorrhage events.

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

Open heart, 2015

Guidelines recommend an early invasive strategy for patients with diabetes with acute coronary sy... more 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. 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, ...

Research paper thumbnail of No gender differences in prognosis and preventive treatment in patients with AMI without significant stenoses

European journal of preventive cardiology, 2012

To investigate possible gender differences in patients with acute myocardial infarction (AMI) and... more 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. Nationwide register-based cohort study. 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. All-cause mortality, recurrent AMI, and redeeming a prescription for a lipid-lowering drug, beta-blocker, clopidogrel, or aspirin within 60 days of discharge. 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). ...